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Effects of phytoestrogens on the reproductive physiology of productive species.

Review

Article in Revista Mexicana de Ciencias Pecuarias · July 2022

DOI: 10.22319/rmcp.v13i3.5878

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Review

Effects of phytoestrogens on the reproductive physiology of productive

species. Review

Miguel Morales Ramírez a

Dinorah Vargas Estradab
Iván Juárez Rodríguez c
Juan José Pérez-Rivero d
Alonso Sierra Reséndiz b
Héctor Fabián Flores González e
José Luis Cerbón Gutiérrez f
Sheila Irais Peña-Corona*g

a
Universidad Autónoma Metropolitana. Unidad Iztapalapa, Departamento de Biología de la
Reproducción, Ciudad de México, México.
b
Universidad Nacional Autónoma de México (UNAM). Facultad de Medicina Veterinaria y
Zootecnia, Departamento de Fisiología y Farmacología, Ciudad de México, México.
c
UNAM. Facultad de Medicina Veterinaria y Zootecnia, Departamento de Medicina
Preventiva y Salud Pública, Ciudad de México, México.
d
Universidad Autónoma Metropolitana. Unidad Xochimilco, Departamento de Producción
Agrícola y Animal, Ciudad de México, México.
e
UNAM. Facultad de Medicina Veterinaria y Zootecnia, Departamento de Genética y
Bioestadística, Ciudad de México, México.
f
UNAM. Facultad de Medicina Veterinaria y Zootecnia, Departamento de Reproducción,
Ciudad de México, México.
g
UNAM. Facultad de Química, Departamento de Biología, Ciudad de México, México.

*Corresponding author: [email protected]

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 Rev Mex Cienc Pecu 2022;13(3):803-829

Abstract:

Phytoestrogens (PEs) are chemical compounds from the secondary metabolism of some
plants, they have a potential effect on the reproductive parameters of domestic animals, acting
as agonists or antagonists of estrogen receptors. The objective of this review is to know the
effects produced by a diet rich in PEs on the reproductive physiology of slaughter animals.
A systematic review was carried out in two databases using keywords related to the effects
produced by the intake of PEs in the diet on the reproduction of animals for slaughter, only
controlled studies developed in vivo were considered. Contradictory results were found, on
the one hand, the intake of a high content of polyphenolic compounds from different fodders,
in the bovine female, was related to the decrease in fertility, presence of abortions and ovarian
cysts; on the other hand, the intake of the high content of PEs induced an increase in the
semen quality of the males of the species: cattle, sheep and leporids, so these effects can be
attributed to the concentration, the type of PEs, sex, species and even the breed of the animal.

Key words: Phytoestrogens, Slaughter animals, Reproductive effects, Coumestans,

Isoflavones, Lignans.

Received: 25/11/2020

Accepted: 04/08/2021

Introduction

In livestock activities, the selection of feed represents one of the main production costs and
is one of the most technically complex aspects for the search for nutritional satisfaction in
the different stages of animal production (breeding, rearing, gestation, lactation, weaning,
growth and fattening), considering their physiological state, age and breed(1-4).

Generally, the feed of slaughter animals (SAs) is based on grains of sorghum and corn, since
they provide a rich source of energy, in addition to other feeds that provide protein, such as
soybeans, canola, alfalfa and clover(2-4). It is essential to highlight that it has been suggested
that changes be made in the feed or forage source in the event of alterations in the
reproduction of SAs(4).

Plant-based feeds are considered a rich source of phytoestrogens (PEs), nonsteroidal

polyphenolic compounds derived from plant metabolism with conformational structure

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similar to 17-β estradiol (E2)(3,5). When ingested by animals, they can act as selective
modulators of estrogen receptors (ERs) and act as endocrine disruptors in an agonistic or
antagonistic manner, depending on the dose ingested(5,6), thus interfering with the synthesis,
secretion, transport and metabolism of reproductive hormones, during embryonic
development and in adult life(6-11).

Nearly 100 PEs have been recognized; these are categorized, according to their chemical
structure, into four classes: isoflavonoids (genistein, daidzein, formononetin); flavonoids
(naringenin, kaempferol); coumestans (coumestrol “COU”), sativol, COU diacetate, 4-
methoxycoumestrol) and lignans (enterolactone and enterodiol)(12,13). Soybeans are the most
abundant source of isoflavones, as it is one of the feeds with the highest content of genistein
and daidzein, while alfalfa and clover contain a high amount of coumarins. It is worth
mentioning that PEs are naturally present in plants, as glycosides, which are hydrolyzed to
aglycone (which is the active form) catalyzed by enzymes present in the digestive
system(14,15).

Through several studies, it has been shown that the intake of PEs causes reproductive
alterations in animals of both sexes, as well as temporary infertility syndromes(16,17).
However, there is also evidence that PEs favor reproduction because they increase the
concentration, motility and volume of spermatozoa necessary for fertilization(18-20).

Due to the economic and productive importance that reproductive alterations represent in the
context of animal production, the objective of this work is to know the potential effect that
feeds rich in PEs have on the reproduction of SAs.

Method

This document was developed in accordance with the PRISMA (Preferred Reporting Items
for Systematic Reviews and Meta-Analyses)(21) statement.

Literature search

A systematic review was conducted on the Web (Figure 1); Google Scholar and PubMed
were used as specialized information search engines with the aim of identifying studies that
explored the effects of PEs present in the diet on the reproductive physiology of SAs, which
have been published in blind peer-reviewed journals, extended abstracts in specialty

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congresses, and in graduate theses between 1996 and 2019. The keywords were established
according to the PICO (Participants, Interventions, Comparisons and Outcomes) principle: P
as slaughter animals (cattle, sheep, goats, equines, pigs, leporids and poultry); I as feeding
with a diet rich in PEs; C as control groups, or groups of animals with low phytoestrogen
diet, or reproductive variables of the same experimental group reported before or after
exposure to the high-phytoestrogen diet; and R as reproductive variables in males and
females. The statement of the topic of the review question was developed as: Do
phytoestrogens present in the diet produce adverse effects on reproductive variables in SAs?
According to the keywords, Google Scholar was first searched and, subsequently, PubMed,
dated until June 2020. Generally, the following words and Boolean operators were used, in
order to identify the studies available on the web: {‘Reproduction’ AND ‘Animals’ AND
‘Phytoestrogens’ AND/OR ‘Fertility’ AND/OR ‘Feed’ AND/OR ‘Isoflavones’ AND/OR
‘Coumestans’, AND/OR ‘Lingans’ AND ‘Cows’ OR ‘Heifers’ OR ‘Bulls’ OR ‘Ewes’ OR
‘Small Rumninant’ OR ‘Sheep’ OR ‘Ovine’ OR ‘Goat’ OR ‘Nanny-goat’ OR ‘Equine’ OR
‘Mare’ OR ‘Horses’ OR ‘Porcine’ OR ‘Sows’ OR ‘Pigs’ OR ‘Leporids’ OR ‘Rabbits’ OR
‘Hens’ OR ‘Rooster’ OR ‘Chickens’} {‘Reproducción’, AND ‘Animales’, AND
‘Fitoestrógenos’ AND/OR ‘Fertilidad’ AND/OR ‘Alimentación’ AND/OR ‘Isoflavonas’
AND/OR ‘Coumestanos’ AND/OR ‘Lignanos’ AND ‘Vacas’ OR ‘Vaquillas’ OR ‘Toros’
OR ‘Pequeños rumiantes’ OR ‘Ovejas’ OR ‘Ovinos’ OR ‘Cabras’ OR ‘Equinos’ OR
‘Yeguas’ OR ‘Caballos’ OR ‘Porcinos’ OR ‘Cerdas’ OR ‘Lepóridos’ OR ‘Conejos’ OR
‘Aves’ OR ‘Gallinas’ OR ‘Gallos’ OR ‘Pollos’}. All the articles were searched in English
and Spanish, were initially examined by reading their abstracts. The full texts of the
documents included preliminarily were reviewed again to select the material to be used.
Figure 1 shows a flowchart that details the selection of studies.

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Figure 1: Flowchart of study search progress

Inclusion and exclusion criteria

The studies considered were those on controlled experiments in vivo, in SAs fed a diet rich
or supplemented with PEs (soybeans, clover, alfalfa) for more than seven days, and that
included the determination of the amount of PEs ingested or sufficient information to
calculate it, in that case, the amount of PEs in the diet (mg/kg of DM [dry matter]) was
obtained from the database of the United States Department of Agriculture(22,23); likewise, to
obtain the amount of daily feed, the ratio of the animals’ weight and the amount of feed
consumed containing PEs (reported in the article) was obtained. Those studies in which the
administration of PEs was not related to feeding, or was administered orally through an
excipient, or when reproductive parameters were not assessed, were excluded.

Data extracted from eligible studies were recorded as follows: species, breed, daily diet, main
effects on reproductive variables, exposure time in days, PEs present in the diet and amount
of PEs (mg/kg of DM).

Risk of bias analysis

The included papers were evaluated by two examiners in order to clarify emerging doubts, a
third party was consulted to identify the presence of bias of randomization, blinding, results
reporting and others (Table 1). To represent the bias analysis, a color scale was proposed: if
the study met the described criterion, the green color was used; if the study was unclear or
there was not enough information for the evaluation of bias, the yellow color was used.

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Table 1: Summary of bias analysis of each included study

The researchers
Blinding of
The random who selected the The study
evaluators The
selection of the sample did NOT is free of
to the results
Reference animal sample know to which other
assigned are
is clearly treatment it sources of
treatment complete
described would be bias
was ensured
assigned
García et al., 2018(24)
Woclawek-Potocka et
al., 2005(25)
Hashem et al., 2016(26)
Rodríguez et al.,
2013(27)
Piotrowska et al.,
2006(28)
Yurrita et al., 2017(29)
Cantero et al., 1996(30)
Pace et al., 2006(31)
Hashem et al., 2018(32)
Pace et al., 2011(33)
Aragadvay-Yungán et
al., 2018(2)
Sierra et al., 2015(34)
Domínguez et al.,
2014(19)
Ferreira-Dias et al.,
2013(35)
Gentao et al., 1999(36)
Yuan et al., 2012(37)
Cardoso et al., 2007(38)
Cardoso et al., 2009(39)
Yousef et al., 2004(18)
Hashem et al., 2008(40)
Saleh et al., 2019(41)
Ni et al., 2007(42)
Lu et al., 2017(43)
Wistedt et al., 2012(44)
Arija et al., 2006(45)
Heng et al., 2017(46)
The green color indicates low risk of bias, the yellow color indicates that it is not clear or there is not enough
information for the evaluation of the criterion, according to the authors’ judgment.

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Results

In the systematic search, 26 specialized documents were finally collected: six on cattle (one
article in Spanish and three in English, a master’s thesis in Spanish and a doctoral thesis in
English); seven on sheep (one in Spanish and four in English, a master’s thesis in Spanish, a
conference abstract in Spanish); one on equines in English; two on pigs in English; four on
leporids in English and six on poultry in English (Table 2). All articles were published
between 1996 and 2019.

Cattle

In a study conducted on 11-month-old Bradford heifers (n=15 per group) fed, six months
before their first service, with 0.8 % of soybeans, calculated based on live weight (LW), (feed
that was considered by the authors to be high in PEs when compared to the usual feeding of
0.3 % LW), a percentage of gestation (%G) of 93 % and an abortion were observed, compared
with the control group, where a 100 % success rate in pregnancy and no cases of abortion
were reported; the authors mention that it is not possible to affirm that feeding with 0.8 %
LW was the cause of abortion, and that this feeding did not affect reproductive parameters(24).
In another study, was evaluated the %G in Holstein/Polish heifers (75 and 25 %) that were
constantly fed 2.5 kg of soybeans, it was observed that the pregnancy rate was not
significantly different compared to the control group, although equol and p-ethyl-phenol
(compounds derived from the metabolism of PEs) were detected in the serum of the
heifers(25). On the other hand, it has been reported that, in Holstein heifers fed clover for five
months, the %G decreased (61.5 %), compared to heifers fed corn silage (92.3 %); the
percentage of heifers that did not become pregnant after several inseminations was higher
(38.46 %) in the group of cows fed clover compared to its control (7.7 %)(26) (Table 2).

In adult Holstein/Polish cows (75 and 25 %) that were fed 2.5 kg of soybeans from a lactation
period prior to mating, they had a %G of 60 % compared to the control group, which showed
100 % gestation(25). In the lactation stage of Holstein cows fed for 60 d with alfalfa or red
clover meal, alterations in the concentrations of E2, progesterone (P4) and luteinizing
hormone (LH) were reported. A significant decrease in E2 was documented in the groups of
cows fed alfalfa (2.32 ± 0.12 pg/mL) or red clover (2.25 ± 0.67 pg/mL) compared to control
cows (4.24 ± 0.31 pg/mL); the concentration of P4 decreased at the end of the
supplementation period in cows fed alfalfa (1.586 ± 0.27 ng/mL) or red clover (0.988 ± 0.3
ng/mL) compared to control animals (2.82 ± 0.34 ng/mL); LH also decreased in cows in the
groups fed alfalfa (3.82 ± 0.22 IU/mL) or red clover (3.7 ± 0.26 IU/mL) compared to control

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cows (6.66 ± 0.39 IU/mL)(27). In another study, it was observed that the concentrations of P4
decreased throughout the estrous cycle in Holstein/Polish black cows when they were fed 2.5
kg of soybeans for 21 d, compared to the control group, this suggests that PEs contained in
soybeans can alter the function of the corpus luteum (CL), it is worth mentioning that the
effects began to be observed between d 15 and 18 after its intake(28) (Table 2). In the only
available study conducted on Angus bulls, with a diet with 10 % of soybeans from weaning
to pre-puberty, an improvement in scrotal growth and semen quality in adulthood was
observed(29).

The documented differences between sexes, derived from the effects produced by PEs, are
biologically plausible, given that PEs are known xenoestrogens that alter the endocrine
system depending on the availability of ERs and target organs of both sexes. In the studies
reviewed, the age of exposure to PEs and the type of PEs determine their biological effect,
observing a greater harmful effect in adult cows kept with feed rich in PEs than in heifers.

Small ruminants

In Manchega ewes that consumed alfalfa ad libitum for 10 mo and that contained COU at the
rate of 25 ppm in autumn, 30 ppm in winter and 17 ppm in spring, it was found that 43 % of
them showed alterations in the genital tract: cysts or microcysts in the endometrium
accompanied by petechiae and ecchymosis in the uterine mucosa, increased glandular
activity and paraovarian cysts(30). There are studies in which no harmful effects on the
reproductive parameters of ewes and males of the Comisana breed are documented, it has
even been suggested that prolonged administration of subterranean clover, with low
formononetin content (less than 10 % of the total isoflavones on a dry basis), induces a
significant improvement in the weight gain of animals and, in males, good carcass and meat
characteristics(31). In another study conducted on pregnant Rahmani ewes, which were fed
for two months prior to calving and until the induction of the next heat (3.5 mo postpartum)
with 849.4 g/kg of DM of Trifolium alexandrinum, no significant differences between groups
in ovarian activity and ovulation in induced heat were documented, but females fed Trifolium
alexandrinum showed shorter estrus duration (20 h) compared to ewes fed corn (34 h), in
which P4 concentrations in the luteal phase of the induced estrus were significantly higher,
compared to treated ewes(32).

In another work conducted on female lambs of the Sarda and Comisana breeds, the effects
of feeding ad libitum with alfalfa or subterranean clover were evaluated, in these animals, no
alterations were observed in the development of the reproductive system, fertility, fecundity,
reproductive performance and calving interval, although animals fed clover had a higher

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weight at puberty, the authors suggest that some clover varieties do not negatively affect the
reproduction of ewes and appear to improve the growth rate of animals(33).

In Creole rams fed 1.1 kg/d of alfalfa contaminated with Pseudopeziza medicaginis at 10, 40
and 70 % for 45 d, a significant decrease in sperm concentration was documented in the rams
fed alfalfa contaminated with the fungus at 40 % and 70 %, compared to the group with
10 %(2). It should be mentioned that fungal infestations caused by Pseudopeziza medicaginis
increase the synthesis of phytoestrogenic substances such as coumarins and isoflavones(2).
Other studies do not report differences between sperm characteristics, for example, in a study
with hybrid Hampshire/Suffolk sheep, which were fed about 1 kg of alfalfa (2.5-6.5 mg of
COU/100 g of alfalfa(22,23)) or 200 g of extruded soybeans (57 mg of genistein/100 g of
extruded soybeans; 31 mg of daidzein/100 g of extruded soybeans(22,23)), daily for 90 d, no
alterations were reported in sperm volume, color, motility and concentration, evaluated in
fresh or cryopreserved semen(34). Likewise, in three-month-old hybrid Katahdin/Pelibuey
lambs fed 23 % of alfalfa for 90 d, no differences were observed in sperm volume, sperm
membrane integrity, total or progressive motility and acrosome status(19) (Table 2). In sheep,
contradictions were found regarding the deleterious or beneficial effects attributed to the
intake of PEs on reproductive variables.

Equines

The effects of PEs due to feeding on equines are poorly described. Conjugate and free (active)
forms of COU and its metabolites have been identified in the plasma of mares fed for 14 d
with alfalfa pellets in increasing concentrations of up to 1 kg/d, during the time of the
experiment, all mares cycled, on day zero half of the mares were in the follicular phase, and
the other half in the luteal phase, on d 13 and 14 of the experiment, all the mares had the
luteal phase(35) (Table 2). The results suggest that PEs affect the length of the estrous cycle
and can prolong luteal function in the mare, due to the induction of the persistence of CL(35).

Pigs

In pregnant sows fed a regular diet supplemented with 0.005 mg of daidzein/kg of LW, in
the peripartum period (from 30 ds prepartum to d 7 postpartum), they showed an increase in
the weight of the litter compared to the control group, which did not consume daidzein; in
addition, the production of milk, colostrum proteins and growth hormone increased by about
12 % in those sows fed that isoflavone(36). In minipigs fed low concentration of isoflavones

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(250 ppm), no negative effects on reproduction were observed; in contrast, when the
concentration increased (500 ppm), the testicular index ((bilateral testicular weight/total body
weight) x 100 %) LH and testosterone (T4) decreased; in addition, there was an increase in
apoptotic germ cells, indicating testicular peroxidation(37) (Table 2).

In sows, feeding supplemented with daidzein favors the weight of the offspring at calving
and milk production, in the case of males, the effect of PEs in the diet depends on the amount
administered, low amounts of PEs favor testicular function.

Leporids

In a study conducted on pregnant does fed a diet of 18 % of soybean meal (13 mg/kg of
isoflavones/body weight) during the stages of gestation, lactation and until the offspring were
33 weeks old, it was observed that males were earlier in the time of onset of puberty compared
to the control group, no significant differences were reported in the morphology of the
reproductive organs, semen quality and sexual behavior(38). In another study, the effect of
exposure to a commercial rabbit diet with 18 % of soybean meal during perinatal period
(intrauterine and lactation) on the morphology of the reproductive organs of males at 26 wk
of age was evaluated. No alterations were observed in the reproductive tract of the male
progeny(39).

In 7-mo-old adult New Zealand male rabbits fed 30 % of Berseem (Trifolium alexandrinum)
hay and supplemented with 2.5-5 mg of isoflavones/kg of body weight every third day for
13 wk, improvements in semen and libido characteristics were documented, since there was
an increase in sperm volume, concentration and percentage of sperm motility(18). When the
effect of a diet rich in soybeans (80 g of soybeans/kg of feed) and flaxseed (100 g of
flaxseed/kg of feed) in adult rabbits was evaluated, increases in the occurrence of
abnormalities in spermatozoa, decrease in libido and in the process of steroidogenesis were
observed, however, when they were crossed with untreated females, pregnancy rate, litter
size and fertility were not affected(40) (Table 2).

The results of the previous studies suggest that the administration of commercial feed, with
a concentration of up to 18 % of soybeans, to pregnant does, does not produce, in the
offspring, alterations in the morphology of the reproductive organs in F1 males. Nor do diets
with percentages less than 80 g of soybean meal or 100 g of flaxseed/kg of feed cause effects
on the reproductive organs of males, the volume of the ejaculate or fertility. No studies
evaluating the effects of PEs directly on the reproductive physiology of females were found
(Table 2).

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Poultry

In a study conducted on 65-wk-old Bovans Brown laying hens(41) fed diets supplemented
with 1 g of flax seeds or fenugreek/kg of feed (rich in PEs, 0.20 mg of isoflavones/kg of DM)
for 6 wk, an increase in the concentrations of E2 and LH, weight and an improvement in shell
thickness at the end of the egg laying cycle were observed, both with the supplementation of
the seeds separately and with their combination (flax and fenugreek)(41). The increase in
eggshell thickness documented in the previous study was also present in another, in which
445-d-old ISA laying hens were fed a diet supplemented with 10 mg of daidzein/kg of
feed(42). In addition, in this last study, a significant increase in the proportion of oviduct
weight to body weight was reported(42). There were no alterations in the width and length of
the egg, nor in the serum concentrations of E2(42). On the other hand, it has been observed
that in 44-wk-old Rugao laying hens fed supplemented diets from 60 to 248 mg of
daidzein/kg of feed for 12 wk, it did not generate significant differences in egg quality or
fertility, although an increase in the hatchability of egg laying was observed(43). Wistedt et
al(44) also reported the absence of effects on reproductive variables in 15-wk-old Lohmann
Selected Leghorn (LSL) and Lohmann Brown (LB) laying hens on the morphology and size
of ovaries and oviducts after being supplemented with 50 mg of daidzein/kg of feed. A
difference in the sensitivity of the breeds to daidzein was observed, since the eggshells were
thicker in LB hens than in LSL hens(44). In 1-d-old Cobb broilers, fed 100, 200 or 300 mg of
extruded or raw beans/kg of feed for 21 d, a decrease in T4 and androstenedione
concentrations was observed with raw bean feeding, in contrast, the administration of
extruded beans increased the same variables(45).

Finally, in 70-d-old young breeding roosters fed a commercial product added with
isoflavones, it was observed that, with 5 mg/kg, testicle weight, concentration of
gonadotropin-releasing hormone (GnRH) and expression of the mRNA of the StAR
enzyme(46) were increased (Table 2). The results of the studies suggest that PEs cause
favorable effects on reproductive variables of male and female poultry.

Bias

In none of the studies included in the present review, the evaluators were blinded to the
assigned treatment, nor in the selection of the sample. In contrast, complete results were
identified in all the papers, and they were free from other sources of bias. More than half of
the included studies used some randomization technique for their experimental
units(18,27,30,31,36,37,38,39,40,41,42,43,45,46).

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Discussion

In ruminants, isoflavones are metabolized in the rumen, which generates estrogenic or non-
estrogenic compounds. Secoisolariciresinol and matairesinol are the precursors of COU,
enterodiol and enterolactone; biochanin A and genistein can be broken down into p-ethyl-
phenol (non-estrogenic); formononetin is metabolized to daidzein and finally to equol, a more
estrogenic compound that is absorbed through the rumen wall(47,48).

The main effects produced by PEs in cattle include hormonal alterations, decrease in %G and
increase in abortions, this depends on the reproductive stage, the time of consumption and
the type of PEs involved. Early embryonic mortality and the increase in the abortion rate can
be explained by the ability of PEs to inhibit the secretion of P4 stimulated by LH(49,50). In
cows, the release of prostaglandins (PG) with luteolytic action is regulated by E2 and P4(51).
PEs and their active metabolites alter the PGE2-F2α ratio, which leads to the non-
physiological production of luteolytic agents during gestation and the estrous cycle(25). In
gestation, the balance between PGE2-F2α is crucial for the maintenance and function of CL,
the recognition of pregnancy, embryo implantation and development, so the stimulation of
PGF2α production can lead to interfere with this balance and embryonic development(52).
PEs as agonists, in non-pregnant animals, reduce the length of the estrous cycle, since during
luteolysis and ovulation, stimulation of PGF2α secretion can accelerate positive feedback
between PGF2α and oxytocin(51,52). On the other hand, PEs, as antagonists, induce alterations
in follicular development and therefore, the absence of estrus(53,54). In addition, a possible
positive relationship between the concentration of isoflavones in blood plasma and the
incidence of silent heat in dairy cattle fed soybeans has been reported(55).

Being structurally similar to E2, PEs act as agonists or antagonists of ERs(7,56). The biological
effects attributed to PEs occur with concentrations around 1,000 times higher than
endogenous E2 concentrations (1-10 nM). This is based on the fact that Woclawek-Potocka
et al reported 1.6 ± 0.3 μM of p-ethyl phenol and 1.2 ± 0.28 μM of equol(25); Piotrowska et
al reported 1.28 ± 0.10 μM of equol and 6.24 ± 0.30 μM of p-ethyl phenol(28); Zdunczyk et
al reported daidzein, genistein, equol and p-ethyl-phenol in a range of 0.1-3.6 μmol/L in cows
that showed reproductive alterations(55). In another study, it was calculated that the intake of
66.8 mg/kg of COU (present in alfalfa) produced plasma concentrations of 13 ng/mL of this
compound, which also turns out to be 1,000 times higher than the concentration of E2 during
estrus(25). Even considering that the biological activity of COU is 160 times lower compared
to that of E2, the amount would be equivalent to six times the effective concentration of E2
in estrus, and therefore, sufficient to induce estrogenic changes similar to those found in the
cow during this phase of the estrous cycle(57). The above data suggest that cows that are
continuously exposed to a diet that includes PEs may show reproductive alterations, contrary

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to what is reported in males, in which feeding with 10 % of soybeans as a source of protein

improves sperm formation and concentration(29).

In sheep, the effects of PEs on reproductive variables are contradictory. In some studies, it
has been suggested that these compounds do not cause alterations as in other species(19,20); in
others, their deleterious effect is evident, even the “Clover Syndrome” has been described,
which consists of infertility, prolapse of the uterus and dystocia(58,59). The main effects
reported in females are morphological alterations in reproductive organs and increased
activity of the endometrial glands, which leads to quantitative and qualitative changes in
cervical mucus, which can hinder fertilization(30,60). It is reported that PEs sensitize the cervix
to estrogenic action, in addition to occupying ERs in the cervix, they also stimulate the
appearance of new binding sites(61). In addition, PEs alter the secretion of the follicle-
stimulating hormone (FSH)(62). In ewes, the number of recruitable follicles depends on FSH
concentrations(63), therefore, PEs are likely to interfere with follicular recruitment.

It has been reported that the factors related to the absence of effects caused by PEs in some
studies are seasonality, the dose of PE ingested and the species and conditions of the plant
used, since it has been documented that, in a single plant species, more than one type of PEs
can be found at different concentrations; for example; under normal conditions, the
concentrations of COU in alfalfa are 1 to 2 mg/kg and in circumstances of defense of the
plant, the concentration of that PE can increase up to 100 mg/kg(64). The concentration of PEs
also depends on the presentation and organ of the plant, for example: the isoflavone content
in raw green soybeans is 48.9 mg/100 g of DM; that of extruded soybeans is 91 mg/100 g of
DM and textured soybeans contain 172.6 mg/100 g of DM(22,23). With respect to flavonoids,
mature soybeans contain 37.41 mg/100 g of DM and green soybeans contain 1.23 mg/100 g
of DM(22,23).

The transition of photoperiods contributes to the regulation of estrous behavior, ovulation,

ERs availability and concentration of endogenous steroids(32). In sheep, it has been suggested
that prolonged ingestion of subterranean clover with PE levels below 0.3 % or ~10 mg/g DM
of alfalfa does not produce infertility or reproductive disorders, it even significantly increases
body growth(33), probably because PEs also stimulate growth hormone(42,65). It has been
suggested that the differences in deleterious effects on reproduction may be due to the type
of isoflavones administered, the difference in the number of ERs and the type of metabolism
between the different species(66). In male sheep, contradictory results were also found,
Aragadvay et al(2) describe reproductive alterations with the feeding of alfalfa contaminated
with Pseudopeziza medicaginis at 40 and 70 %; other studies do not report harmful
effects(19,34). The reason why this difference in results exists is not described yet, probably
due to the difference in the sensitivity of steroidogenic compounds between breeds of the
same species, as reported in other animal models(67), it is even likely that male sheep are less

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susceptible to the effect of phytoestrogens(20) or that some plant varieties do not negatively
affect the reproduction of ewes(20,33).

According to the criteria established in this review, no published studies related to goats were
found. However, it has been reported that goats constantly fed 30 % of dehydrated alfalfa
had an incidence of 20 % of rectal or vaginal prolapses in the last month of gestation(68).

In a case report of mares fed 5-8 kg/d of mixture of alfalfa and clover hay for at least 5 mo,
uterine edema, absence of ovulation and accumulation of uterine fluid and return to normal
ovarian cyclicity within 2 to 3 wk after withdrawal of the feed rich in PEs, were observed(35).
The mechanism of absorption of PEs is not fully described; in this species, digestion is very
fast and feed can pass through the stomach and small intestine within the first 5 h(69). This
was confirmed in a study in which active forms of COU reached their highest level between
1 and 3.5 h after ingestion(35). The amount of PEs in the pasture depends on the season of the
year, since a decrease in COU and its metabolites was found when evaluated from November
to March and it is known that its synthesis increases under adverse conditions for plants(35).
It is worth mentioning that the dehydration of alfalfa to produce pellets could reduce
estrogenic activity(70). Therefore, the exposure time, the presentation of PEs and the season
of the year are fundamental for the effects to occur.

The effects of PEs, present in the diet of pigs, on reproductive variables are few, in contrast
to the amount of data on estrogenic effects of feed contaminated with mycotoxins, or works
in which the effect of isoflavones on meat quality and growth is studied(71-73). Daidzein and
genistein are the main isoflavones contained in soybean meal, which is the basic protein
ingredient in the diet of pigs, and it is known that both represent 88 % of the isoflavones
circulating in the blood(73). One of the effects of feeding sows with diets containing PEs in
the last third of gestation is an increase in the weight of animals, this may be due to the
positive effect produced by PEs on growth hormone concentrations(74). In males, the effect is
much more evident, since, in the fetal stage, the concentrations of circulating estrogens are
low, and the presence of PEs would stimulate growth due to a change in metabolism,
proliferation and differentiation of skeletal muscle(75). The increase in milk production and
better milk quality in sows fed isoflavones could be due to their agonist effect on insulin-like
growth factor-1 (IGF-1) and prolactin reported in periparturient sows(76) or to a better balance
of antioxidants(77). In males, a positive effect on reproduction has been identified when low
concentrations of PEs are administered(37). This has been attributed to the binding of
isoflavones to ERs in the hypothalamus, pituitary gland and testicles, thus stimulating
spermatogenesis, sperm maturation and gonadal growth(6).

As for leporids, it is reported that females are more sensitive to the effect of environmental
estrogens(38). In male rabbits, intrauterine and lactational administration of PEs do not induce
deleterious effects on semen production or sexual behavior, it has even been suggested that

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soybean meal can be used as part of the normal diet in pregnant females without reproductive
damage to the progeny(38,39). The beneficial influence of isoflavones on semen parameters
has been attributed to their antioxidant effect because they reduce the production of hydrogen
peroxide and protect spermatozoa against oxidative damage(18). In addition, in adult males,
estrogen plays a major role in the prevention of the apoptosis in germ cells through its
paracrine or autocrine actions in the testicles(32). The type of PEs consumed by rabbits also
influences the final effect, for example, lignans suppress T4 synthesis more strongly during
spermatogenesis and libido, compared to isoflavones(32).

In poultry, as in other domestic animals, PEs can act as agonists/antagonists, depending on

the dose, tissue type, ER subtype and presence of endogenous hormones, therefore they are
considered selective modulators of ERs(78). In poultry, the effects produced by the
consumption of PEs are related to the genetic component, since lines of LB and LSL hens
showed different sensitivity to these compounds(44); this could be due to the fact that there is
a difference in the location and expression of ERs ß in uterine capillaries between genetic
lines, which could influence the obtaining of greater weight of the oviduct(44).

In bird males, it was observed that a diet rich in PEs promotes testicular growth due to the
increase in hormonal secretion, probably due to the regulatory participation of isoflavones in
the feedback mechanism of the hypothalamic-pituitary-gonadal axis(79), which in turn
regulates the secretion of FSH, LH and T4 that promotes the growth and maturation of Sertoli
and Leydig cells. The administered dose also has an important role, it is documented that
genistein has partial agonist effects in roosters at doses of 50-200 mmol/kg, and acts as an
antagonist at doses of 400-500 mol/kg(78); in addition, PEs have the ability to inhibit the
activity of steroidogenic enzymes, and influence the viability of sex hormones through the
regulation of their binding proteins; they alter brain centers related to sexual behavior as they
cross the blood-brain barrier and bind to ER α and ß(80).

Finally, the metabolism of dietary PEs is predominantly determined by gastrointestinal

bacterial metabolism and depends on the reproductive stage, for example, during gestation,
genistein has the potential to influence fetal metabolism and growth; in the colon, genistein
can be metabolized to dihydrogenysteine or 6’-hydroxy-O-desmethylangolensine, while
daidzein can be reduced to dihydrodaidzein and converted into O-desmethylangolensin or
equol, these metabolites can be absorbed or metabolized into phenols in the colon lumen(81).
After the consumption of PEs, these are deconjugated by the intestinal bacterial flora,
reabsorbed, re-conjugated in the liver and excreted in the urine(25,61). The demethylation of
these compounds occurs in the intestine by acetogenic bacteria and in the liver(81). Therefore,
the intestine microbiome present in each species will influence the final effect of PEs on
productive and reproductive variables.

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Conclusions

Based on the papers reviewed and discussed, it is concluded that phytoestrogens cause
alterations in the reproductive physiology of slaughter animals considering four factors: 1)
The plant species consumed; 2) The season of the year in which the plant species is
consumed; 3) The particularities of the animals (metabolism, age, breed, species and sex)
and 4) The processing conditions of the plant. Future studies should be carried out to
elucidate the endocrine mechanisms of the actions of PEs in the reproduction of animals. It
is necessary to reevaluate the ingredients that make up the feeds of the different productive
animals.

Literature cited:
1. Meléndez P, Bartolomé J. Advances on nutrition and fertility in dairy cattle: Review. Rev
Mex Cienc Pecu 2017;8(4):407-417.

2. Aragadvay-Yungán R, Novillo-Rueda M, Núñez-Torres O, Rosero-Peña Herrera M,

Lozada-Salcedo E. Calidad seminal de carneros alimentados con dietas que contienen
alfalfa (Medicago sativa) contaminada con Pseudopeziza medicaginis. Rev Ecua Invest
Agrope 2018;2(1):14-19.

3. Pérez-Rivero JJ, Setién A, Martínez-Maya JJ, Pérez-Martínez M, Serrano H. Los

fitoestrógenos y el efecto de su consumo en diferentes órganos y sistemas de animales
domésticos. Agric Tec 2007;67(3):325-331.

4. Magnusson U. Environmental endocrine disruptors in farm animal reproduction: research

and reality. Reprod Domest Anim 2012;47(Suppl 4):333-337.

5. Di Gioia F, Petropoulos SA. Phytoestrogens, phytosteroids and saponins in vegetables:

Biosynthesis, functions, health effects and practical applications. Adv Food Nutr Res
2019;90:351-421.

6. Adams NR. Detection of the effects of phytoestrogens on sheep and cattle. J Anim Sci
1995;73(5):1509-1515.

7. Almstrup K, Fernández MF, Petersen JH, Olea N, Skakkebæk NE, Leffers H. Dual effects
of phytoestrogens result in u-shaped dose-response curves. Environ Health Perspect
2002;110(8):743-748.

8. Cederroth CR, Zimmermann C, Nef S. Soy, phytoestrogens and their impact on

reproductive health. Mol Cell Endocrinol 2012;355(2):192-200.

818
 Rev Mex Cienc Pecu 2022;13(3):803-829

9. Ropero AB, Alonso-Magdalena P, Ripoll C, Fuentes E, Nadal A. Rapid endocrine

disruption: environmental estrogen actions triggered outside the nucleus. J Steroid
Biochem Mol Biol 2006;102(1-5):163-169.

10. Shanle EK, Xu W. Endocrine disrupting chemicals targeting estrogen receptor signaling:
identification and mechanisms of action. Chem Res Toxicol 2011;24(1):6-19.

11. Whitten PL, Patisaul HB. Cross-species and interassay comparisons of phytoestrogen
action. Environ Health Perspect 2001;109(Suppl 1):5-20.

12. Nilsson S, Makela S, Treuter E, Tujague M, Thomsen J, Andersson Gr, et al. Mechanisms
of Estrogen Action. Phys Rev 2001;81(4):1535-1565.

13. Wocławek-Potocka I, Mannelli C, Boruszewska D, Kowalczyk-Zieba I, Waśniewski T,

Skarżyński DJ. Diverse effects of phytoestrogens on the reproductive performance: cow
as a model. Int J Endocrinol 2013;2013:650984.

14. Bonilla CA. Isoflavonas en ginecología, terapia no convencional. Rev Colomb de Obstet
y Ginecol 2004;55(3):209-217.

15. Wang H, Murphy PA. Isoflavone Content in Commercial Soybean Foods. J Agric Food
Chem 1994;42(8):1666-1673.

16. Peña-Corona S, León P, Mendieta E, Villanueva M, Salame A, Vargas D, et al. Effect of

a single application of coumestrol and/or dimethyl sulfoxide, on sex hormone levels and
vaginal cytology of anestrus bitches. Vet Méx 2019;6(1):1-15.

17. Pérez-Rivero JJ, Martínez-Maya JJ, Pérez-Martínez M, Aguilar-Setién Á, Serrano H.

Efecto del coumestrol sobre la producción espermática y la conducta de exploración
olfatoria de perros estimulados con moco vaginal estral. Vet Méx 2009;40(1):9-16.

18. Yousef MI, Esmail AM, Baghdadi HH. Effect of isoflavones on reproductive
performance, testosterone levels, lipid peroxidation, and seminal plasma biochemistry
of male rabbits. J Environ Sci Health, Part B 2004;39(5-6):819-833.

19. Domínguez-Rebolledo AE, Alcaraz-Romero A, Cantón-Castillo JG, Loeza-Concha H,

Ramón-Ugalde J. Efecto de la Alfalfa (Medicago Sativa L.) en la dieta sobre la calidad
de los espermatozoides epididimarios de ovinos Katahdin con Pelibuey. Reunión
Científica Tecnológica, Forestal y Agropecuaria Tabasco 2014 y III Simposio
internacional en producción agroalimentaria tropical. Tabasco: Instituto Nacional de
Investigaciones Forestales, Agrícolas y Pecuarias 2014:186-189.

20. Valderrabano J. Alteraciones reproductivas asociadas al consumo de fitoestrógenos.

Investigación Agraria Producción y Sanidad Animal 1992;7(2):115-124.

819
 Rev Mex Cienc Pecu 2022;13(3):803-829

21. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items
for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med
2009;6(7):e1000097.

22. Bhagwat S, Haytowitz DB, Holden JM. USDA database for the isoflavone content of
selected foods, release 2.0. Maryland: US Depart of Agricult 2008;15.

23. Bhagwat S, Haytowitz DB, Holden JM. USDA database for the flavonoid content of
selected foods, Release 3.1. US Depart of Agricult: Beltsville, MD, USA. 2014.

24. García DC, Martín AA, Vella MA, Nasca JA, Roldan Olarte EM. Evaluación de la
alimentación con distintos niveles de inclusión de soja en la recría de vaquillonas. Vet
Arg 2018;35(357)1-9.

25. Woclawek-Potocka I, Acosta TJ, Korzekwa A, Bah MM, Shibaya M, Okuda K, et al.
Phytoestrogens Modulate Prostaglandin Production in Bovine Endometrium: Cell Type
Specificity and Intracellular Mechanisms. Exp Biol Med 2005;230(5):326-333.

26. Hashem NM, El-Azrak KM, Sallam SMA. Hormonal concentrations and reproductive
performance of Holstein heifers fed Trifolium alexandrinum as a phytoestrogenic
roughage. Anim Reprod Sci 2016;170:121-127.

27. Rodríguez MCE. Determinación del contenido de fitoestrógenos presentes en la alfalfa

(Medicago sativa) y el trébol rojo (Trifolium pratense) y evaluación de su efecto sobre
el perfil hormonal en vacas Holstein en la Granja Tungüavita Paipa-Boyacá [tesis
maestría]. Colombia, Tunja: Universidad Pedagógica y Tecnológica de Colombia; 2013.

28. Piotrowska KK, Woclawek-Potocka I, Bah MM, Piskula MK, Pilawsk W, Bober A, et
al. Phytoestrogens and their metabolites inhibit the sensitivity of the bovine corpus
luteum to luteotropic factors. J Reprod Dev 2006;52(1) 33-41.

29. Yurrita SC. Evaluation of dietary phytoestrogen exposure on growth, semen parameters,
and reproductive anatomy development of growing Angus bulls [doctoral thesis]. USA,
Texas: Angelo State University; 2017.

30. Cantero A, Sancha JL, Flores JM, Rodriguez A, Gonzalez T. Histopathological changes
in the reproductive organs of Manchego ewes grazing on lucerne. J Vet Med Seri A
1996;43(6):325-330.

31. Pace V, Carbone K, Spirito F, Iacurto M, Terzano M, Verna M, et al. The effects of
subterranean clover phytoestrogens on sheep growth, reproduction and carcass
characteristics. Meat Sci 2006;74(4):616-622.

820
 Rev Mex Cienc Pecu 2022;13(3):803-829

32. Hashem NM, El-Azrak KM, El-Din ANM, Sallam SM, Taha TA, Salem MH. Effects of
Trifolium alexandrinum phytoestrogens on oestrous behaviour, ovarian activity and
reproductive performance of ewes during the non-breeding season. Anim Reprod Sci
2018;196:1-8.

33. Pace V, Conto G, Carfi F, Chiariotti A, Catillo G. Short-and long-term effects of low
estrogenic subterranean clover on ewe reproductive performance. Small Ruminant Res
2011;97(1-3):94-100.

34. Sierra SLA. Evaluación del efecto de los fitoestrógenos presentes en la alfalfa (Medicago
sativa) sobre la calidad del semen ovino fresco y criopreservado [tesis de maestria].
Colombia, Tunja: Univesidad Pedagógica y Tecnológica de Colombia; 2015.

35. Ferreira-Dias G, Botelho M, Zagrajczuk A, Rebordão MR, Galvão AM, Bravo PP, et al.
Coumestrol and its metabolite in mares' plasma after ingestion of phytoestrogen-rich
plants: potent endocrine disruptors inducing infertility. Theriogenology 2013;80(6):684-
692.

36. Gentao L, Yuanlin Z, Weihua C, Jie C, Zhengkang H. Effect of daidzein fed to pregnant
sows on milk production and the levels of hormones in colostrum. Nanjing Agric Univ
1999;22(1):69-72.

37. Yuan X, Zhang B, Li L, Xiao C, Fan J, Geng M, et al. Effects of soybean isoflavones on
reproductive parameters in Chinese mini-pig boars. J Anim Sci Biotechnol
2012;3(1):31.

38. Cardoso JR, Báo SN. Effects of chronic exposure to soy meal containing diet or soy
derived isoflavones supplement on semen production and reproductive system of male
rabbits. Anim Reprod Sci 2007;97(3-4):237-245.

39. Cardoso J, Bao S. Morphology of reproductive organs, semen quality and sexual
behaviour of the male rabbit exposed to a soy-containing diet and soy-derived
isoflavones during gestation and lactation. Reprod Dom Anim 2009;44(6):937-942.

40. Hashem NM, Abo-Elsoud MA, El-Din ANM, Kamel KI, Hassan GA. Prolonged
exposure of dietary phytoestrogens on semen characteristics and reproductive
performance of rabbit bucks. Dom Anim Endocrinol 2018;64:84-92.

41. Saleh AA, Ahmed EAM, Ebeid TA. The impact of phytoestrogen source supplementation
on reproductive performance, plasma profile, yolk fatty acids and antioxidative status in
aged laying hens. Reprod Dom Anim 2019;54(6):846-854.

821
 Rev Mex Cienc Pecu 2022;13(3):803-829

42. Ni Y, Zhu Q, Zhou Z, Grossmann R, Chen J, Zhao R. Effect of dietary daidzein on egg
production, shell quality, and gene expression of ER-α, GH-R, and IGF-IR in shell
glands of laying hens. J Agri Food Chemis 2007;55(17):6997-7001.

43. Lu J, Qu L, Shen MM, Li SM, Dou TC, Hu YP, et al. Safety evaluation of daidzein in
laying hens: Effects on laying performance, hatchability, egg quality, clinical blood
parameters, and organ development. Poult Sci 2017;96(7):2098-2103.

44. Wistedt A, Ridderstråle Y, Wall H, Holm L. Effects of phytoestrogen supplementation

in the feed on the shell gland of laying hens at the end of the laying period. Anim Reprod
Sci 2012;133(3-4):205-213.

45. Arija I, Centeno C, Viveros A, Brenes A, Marzo F, Illera JC, et al. Nutritional evaluation
of raw and extruded kidney bean (Phaseolus vulgaris L. var. Pinto) in chicken diets.
Poult Sci 2006;85(4):635-644.

46. Heng D, Zhang T, Tian Y, Yu S, Liu W, Xu K, et al. Effects of dietary soybean

isoflavones (SI) on reproduction in the young breeder rooster. Anim Reprod Sci
2017;177:124-131.

47. Cepeda VA. Disociación de respuestas estrogénicas en presencia de un extracto

alcohólico de planta chilena, evaluadas en útero de rata pre-púber [tesis pregrado]. Chile,
Santiago: Universidad de Chile; 2008.

48. Cox RI, Braden AW. The metabolism and physiological effects of phyto-oestrogens in
livestock. Proc Aust Soc Anim Prod 1974;10:122.

49. McGarvey C, Cates PS, Brooks AN, Swanson IA, Milligan SR, Coen CW, et al.
Phytoestrogens and gonadotropin-releasing hormone pulse generator activity and
pituitary luteinizing hormone release in the rat. Endocrinology 2001;142(3):1202-1208.

50. Hughes CL, Kaldas RS, Weisinger AS, McCants CE, Basham KB. Acute and subacute
effects of naturally occurring estrogens on luteinizing hormone secretion in the
ovariectomized rat: Part 1. Reprod Toxicol 1991;5(2):127-132.

51. Goff AK. Steroid hormone modulation of prostaglandin secretion in the ruminant
endometrium during the estrous cycle. Biol Reprod 2004;71(1):11-16.

52. McCracken JA, Custer EE, Lamsa JC. Luteolysis: a neuroendocrine-mediated event.
Physiol Rev 1999;79(2):263-323.

53. Dubey RK, Rosselli M, Imthurn B, Keller PJ, Jackson EK. Vascular effects of
environmental oestrogens: implications for reproductive and vascular health. Hum
Reprod Update 2000;6(4):351-363.

822
 Rev Mex Cienc Pecu 2022;13(3):803-829

54. Rosselli M, Reinhart K, Imthurn B, Keller PJ, Dubey RK. Cellular and biochemical
mechanisms by which environmental oestrogens influence reproductive function. Hum
Reprod Update 2000;6(4):332-350.

55. Zdunczyk S, Piskula M, Janowski T, Baranski W, Ras M. Concentrations of isoflavones

in blood plasma of dairy cows with different incidence of silent heat. Bull Vet Inst
Pulawy 2005;49:189-191.

56. Beato M. Gene regulation by steroid hormones. Cell 1989;56(3):335–344.

57. Romero RCM, Tarrago CMR, Muñoz MR, Arista RR, Rosado GA. Síndrome estrogénico
en vacas lecheras por consumo de alfalfas con grandes cantidades de coumestrol. Vet
Méx 1997;28(1):25-30.

58. Mustonen E, Taponen S, Andersson M, Sukura A, Katila T, Taponen J. Fertility and

growth of nulliparous ewes after feeding red clover silage with high phyto-oestrogen
concentrations. Animal 2014;8(10):1699-1705.

59. Bennetts HW, Underwood EJ, Shier FL. A specific breeding problem of sheep on
subterranean clover pastures in Western Australia. Aust Vet J 1946;22(1):2-12.

60. Adams NR. Permanent infertility in ewes exposed to plant oestrogens. Aust Veter J
1990;67(6):197-201.

61. Tang BY, Adams NR. Changes in oestradiol-17β binding in the hypothalami and pituitary
glands of persistently infertile ewes previously exposed to oestrogenic subterranean
clover: evidence of alterations to oestradiol receptors. J Endocrinol 1978;78(2):171-177.

62. Arispe SA, Adams B, Adams TE. Effect of phytoestrogens on basal and GnRH-induced
gonadotropin secretion. J Endocrinol 2013;219(3):243-250.

63. Driancourt MA, Gibson WR, Cahill LP. Follicular dynamics throughout the oestrous
cycle in sheep. A review. Reprod Nutr Dev 1985;25(1A):1-15.

64. Cortés-Sánchez ADJ, León-Sánchez JR, Jiménez-González FJ, Díaz-Ramírez M,

Villanueva-Carvajal A. Alimentos funcionales, alfalfa y fitoestrógenos. Revista Mutis
2016;6(1):28-40.

65. Misztal T, Wañkowska M, Górski K, Romanowicz K. Central estrogen-like effect of

genistein on growth hormone secretion in the ewe. Acta Neurobiol Exp (Wars)
2007;67(4):411-419.

66. Lundh T. Metabolism of estrogenic isoflavones in domestic animals. Proc Soc Exp Biol
Med 1995;208(1):33-39.

823
 Rev Mex Cienc Pecu 2022;13(3):803-829

67. Takahashi O, Oishi S. Testicular toxicity of dietarily or parenterally administered

bisphenol A in rats and mice. Food Chem Toxicol 2003;41(7):1035-1044.

68. Gutiérrez J, Castañón J. Prolapsos rectales y vaginales en cabras atribuibles al exceso de

alfalfa deshidratada. En: Producción ovina y caprina. Jornadas de la Sociedad Española
de Ovinotecnia y Caprinotecnia de la Universidad de Castilla-La Mancha. Castilla.
1994:239-242.

69. Van Weyenberg S, Sales J, Janssens G. Passage rate of digesta through the equine
gastrointestinal tract: A review. Livestock Sci 2006;99(1):3-12.

70. Bickoff EM, Booth AN, Livingston AL, Hendrickson AP. Observations on the effect of
drying on estrogenic activity of alfalfa samples of varying maturity. J Anim Sci
1960;19(3):745-753.

71. Gatta D, Russo C, Giuliotti L, Mannari C, Picciarelli P, Lombardi L, et al. Influence of

partial replacement of soya bean meal by faba beans or peas in heavy pigs’ diet on meat
quality, residual anti-nutritional factors and phytoestrogen content. Arch Anim Nutr
2013;67(3):235-247.

72. Groot MJ. Phyto-estrogenic activity of protein-rich feeds for pigs. RIKILT-Institute of
Food Safety 2004. https://edepot.wur.nl/29220. Accessed Mar 8, 2021.

73. Kuhn G, Hennig U, Kalbe C, Rehfeldt C, Ren M, Moors S, et al. Growth performance,
carcass characteristics and bioavailability of isoflavones in pigs fed soy bean based diets.
Arch Anim Nutr 2004;58(4):265-276.

74. Liu G, Chen J, Han Z. Effects of isoflavonic phytoestrogen daiazein to lactating sows.
Anim Husb Vet Med 1997;29:5-7.

75. Ren MQ, Kuhn G, Wegner J, Nurnberg G, Chen J, Ender K. Feeding daidzein to late
pregnant sows influences the estrogen receptor beta and type 1 insulin-like growth factor
receptor mRNA expression in newborn piglets. J Endocrinol 2001;170(1):129-135.

76. Farmer C, Robertson P, Xiao C, Rehfeldt C, Kalbe C. Exogenous genistein in late

gestation: effects on fetal development and sow and piglet performance. Animal.
2016;10(9):1423-1430.

77. Hu YJ, Gao KG, Zheng CT, Wu ZJ, Yang XF, Wang L, et al. Effect of dietary
supplementation with glycitein during late pregnancy and lactation on antioxidative
indices and performance of primiparous sows. J Anim Sci 2015;93(5):2246-2254.

78. Ratna, WN. Inhibition of estrogenic stimulation of gene expression by genistein. Life Sci
2002;71(8):865–877.

824
 Rev Mex Cienc Pecu 2022;13(3):803-829

79. Nicholls J, Lasley BL, Nakajima ST, Setchell KD, Schneeman BO. Effects of soy
consumption on gonadotropin secretion and acute pituitary responses to gonadotropin-
releasing hormone in women. J Nutr 2002;132(4):708-714.

80. Wu N, Xu W, Cao GY, Yang YF, Yang XB, Yang XW. The blood-brain barrier
permeability of lignans and malabaricones from the seeds of Myristica fragrans in the
MDCK-pHaMDR cell monolayer model. Molecules 2016;21(2):134.

81. Kelly GE, Nelson C, Waring MA, Joannou GE, Reeder AY. Metabolites of dietary (soya)
isoflavones in human urine. Clin Chim Acta 1993;223(1-2):9-22.

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Table 2: Summary of the main effects of phytoestrogens (PEs) on productive species

Amount of PEs
Condition and Exposure according to the species
Species Daily intake Main effects Authors and year
breed (days) and presentation of the
plant (mg/kg of DM)
Woclawek-
Holstein/Polish 2.5 kg of
Decrease in PR 300 1900 of GEN and DAI Potocka et al.,
cows soybeans
2005(25)
Increase in E2, decrease in P4 Rodríguez et al.,
Holstein cows ~5 kg of alfalfa 60 ~25-65 of COU
and LH 2013(27)
~5 kg of red Increase in E2, decrease in P4 ~100 of GEN and 110 of Rodríguez et al.,
Holstein cows 60
clover and LH DAI 2013(27)
Holstein/Polish 2.5 kg of Piotrowska et al.,
Decrease in P4 21 1900 of GEN and DAI
cows soybeans 2006(28)
Cattle 2.22 of kg Decrease in PR, increase in ~570 of GEN and 310 of García et al.,
Bradford heifers 300
soybeans abortions, not significant DAI 2018(24)
Woclawek-
Holstein/Polish 2.5 kg of
No difference in PR 21 1900 of GEN and DAI Potocka et al.,
heifers soybeans
2005(25)
6.60 of GEN, 8.05 of DAI,
Decrease in PR and P4 Hashem et al.,
Holstein heifers ~7 kg of clover 150 2.85 of FOR and 282.5 of
Increase in E2 2016(26)
BI
~800 g of ~135 of GEN and 6.32 of Yurrita et al.,
Angus male calves Increase in sperm concentration 360
soybean meal DAI 2017(29)
Alfalfa pasture Endometrial and paraovarian Cantero et al.,
Manchega ewes 300 17-30 of COU
ad libitum cysts 1996(30)
Sheep 800 g of
6.60 of GEN, 8.05 of DAI, Hashem et al.,
Rahmani ewes subterranean Shorter estrus duration 180
2.85 of FOR and 265 of BI 2018(32)
clover

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Subterranean
Comisana female 797 of GEN, DAI, FOR
clover pasture No effects on reproduction 60 Pace et al., 2006(31)
lambs and BI
ad libitum
Alfalfa pasture No alterations in reproductive 900-10210 of GEN, BI and
Sarda female lambs 60 Pace et al., 2011(33)
ad libitum system, fertility and fecundity FOR
Subterranean
No alterations in reproductive 900-10210 of GEN, BI and
Sarda female lambs clover pasture 60 Pace et al., 2011(33)
system, fertility and fecundity FOR
ad libitum
Subterranean
Comisana female No alterations in reproductive 810-880 of GEN, BI and
clover pasture 600 Pace et al., 2011(33)
lambs parameters FOR
ad libitum
Aragadvay-
Sperm concentration inverse to
Creole rams ~1 kg of alfalfa 45 ~25-65 of COU Yungán et al.,
the dose
2018(2)
Hampshire/Suffolk 1 kg of alfalfa No alterations in sperm Sierra et al.,
90 ~25-65 of COU
rams meal parameters 2015(34)
200 g of
Hampshire/Suffolk No alterations in sperm ~570 of GEN and 310 of Sierra et al.,
extruded 90 (34)
rams parameters DAI 2015
soybeans
Katahdin/Pelibuey No alterations in sperm Domínguez et al.,
~230 g of alfalfa 90 ~25-65 of COU
male lambs parameters or morphology 2014(19)
Subterranean
Comisana male 797 of GEN, DAI, FOR
clover pasture No effects on reproduction 60 Pace et al., 2006(31)
lambs and BI
ad libitum
1 kg of alfalfa High concentrations of COU in Ferreira-Dias et
Equines Lusitano mares 14 ~25-65 of COU
pellets serum al., 2013(35)
Large
Gentao et al.,
Pigs White/Erhualian ~1.5 mg of DAI Increase in milk production 37 -
1999(36)
pregnant sows

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At low doses, increase in

~6.75–27 mg of
testicular index; at high doses, Yuan et al.,
Minipig boars soybean 60 125-500 of ISO (37)
decrease in testicular index, LH 2012
isoflavones
and T4
No effect on reproductive
New Zealand ~20 g of ~135 of GEN and 632 of Cardoso et al.,
organs, semen quality and ~256
pregnant does soybean meal DAI 2007(38)
sexual behavior of F1
New Zealand ~32 g of No alterations in reproductive ~135 of GEN and 632 of Cardoso et al.,
60
bucks soybean meal organs DAI 2009(39)
Improvement in the
Leporids New Zealand 7.13-14.25 mg Yousef et al.,
characteristics of semen and 91 -
bucks of ISO* 2004(18)
libido
~15.44 g of It does not affect semen fertility, 240.4 of DAI and 131 ofHashem et al.,
Line V bucks 84
soybeans decrease in T4 GEN 2018(40)
~19.3 g of It does not affect semen fertility, 368 of SECOI and 52.8 of
Hashem et al.,
Line V bucks 84
flaxseed decrease in T4 DAI 2018(40)
Bovans Brown ~120 mg of Saleh et al.,
Increase in LH, FSH, E2 42 -
hens flax 2019(41)
Bovans Brown ~131 mg of ~0.1 of DAI and 0.1 of Saleh et al.,
Increase in LH, E2 42
hens fenugreek GEN 2019(41)
~128 mg of
Bovans Brown flax and 128 ~0.1 of DAI and 0.1 of Saleh et al.,
Poultry Increase in LH, FSH, E2 42
hens mg of GEN 2019(41)
fenugreek
~1.2 mg of
ISA hens Increase in oviduct weight 63 - Ni et al., 2007(42)
DAI
~5.4-22.57 mg
Rugao hens No effect on fertility 84 - Lu et al., 2017(43)
of DAI

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No changes in morphology and

Lohmann Brown Wistedt et al.,
~5 mg of DAI size of ovaries and oviducts 84 -
hens 2012(44)
high sensitivity to DAI
Selected Leghorn No changes in morphology and Wistedt et al.,
~5 mg of DAI 84 -
hens size of ovaries and oviducts 2012(44)
~0.75 mg of Increase in testicle weight, Heng et al.,
Young breeders 63 - (46)
ISO GnRH 2017
~2.38-7.14 mg
Increase in T4 and Arija et al.,
of extruded 21 -
androstenedione 2006(45)
Cobb chickens beans
~2.38-7.14 mg Decrease in T4 and Arija et al.,
21 - (45)
of raw beans androstenedione 2006
BI= Biochanin A; COU= Coumestrol; DAI= Daidzein; E2= 17-ß estradiol; FOR= Formononetin; F1= Filial generation 1; GEN= Genistein; GLY= Glycitein;
GnRH= Gonadotropin-releasing hormone; ISO= Isoflavones; LH= Luteinizing hormone; MCOU= Methoxycoumestrol; PEP= Para-ethyl-phenol; P4=
Progesterone; SECOI= Secoisolariciresinol; T4= Testosterone; PR= Pregnancy rate; -= Not applicable; *= Every 3 days; ~= approximate calculation.

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