Human Reproduction

Reproductive events in humans :

​ Gametogenesis : formation of haploid gametes, ova in females and sperm in males from
their respective diploid mother cells.
​ Insemination : the transfer of sperms into the female genital tract.
​ Fertilization : the process of fusion of haploid male and female gametes to form diploid
zygote.
​ Implantation : the process of attachment of blastocyst to the embryonic wall of the uterus.
​ Gestation : is the duration between conception and childbirth
​ Parturition : delivery of the baby.
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❖​ The Male reproductive system :

The human male reproductive system comprises the following :

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a.​ Primary sex organ or the testis
b.​ Accessory ducts ……… 1. Rete testis
2. Vasa efferentia
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3. Epididymis
4. Vas deferens
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c.​ Accessory glands………... 1. Seminal vesicles
​ ​ ​ 2. Prostate gland
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3. Cowper’s gland / Bulbourethral gland
d.​ External genitalia – the penis
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The testes :
Testes are in a pair and situated outside the abdominal cavity.
They are embedded within a pouch called scrotum so as to maintain the temperature of the testes
2-2.5oC below the normal internal body temperature to facilitate spermatogenesis.
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Testis is oval shaped and 4-5 cm in length and 2-3 cm in width.

Testis is lined by three layers- outermost layer the tunica vaginalis, middle layer the tunica
vasculosa and innermost the tunica albuginea.
Tunica albuginea undergoes infoldings to form 200-250 compartments called the testicular
lobules.
Each lobule contains 2-3 highly coiled seminiferous tubules in which the sperms are produced.

Anatomy of testis / T.S of seminiferous tubules :

Seminiferous tubules appear rounded or oval and are held together by connective tissue.
Each seminiferous tubule is lined on the outside by germinal epithelium and on the inside by two
types of cells called the Male germ cells and the Sertoli cells.
Male germ cells – these are the reproductive cells. They are smaller, circular or cuboidal in shape
and more in number.
They undergo meiotic divisions to produce the spermatogonia.
Sertoli cells – these are the non-reproductive cells. They are larger in size and elongated in shape.
Less in number compared to the germ cells.
They provide nutrition to the spermatogonia.
Secrete androgen binding protein required for maturation of the sperm.
Produce hormone Inhibin to inhibit the production of sperms when more sperms are present in the
seminiferous tubules.
The regions outside the seminiferous tubules suspended in the connective tissue are called the
interstitial spaces containing small blood vessels and groups of cells called the Interstitial cells or
the Leydig cells.
Leydig cells secrete testicular hormone-androgens/ testosterone which is responsible for the
secondary sexual characters in males.

Accessory ducts :
1.​ Rete testis – network of tiny tubules in the testis into which the seminiferous tubules open into.
2.​ Vasa efferentia – tiny ducts that leave the testis and open into epididymis located along the
posterior surface of each testis and thus transfer the spermatozoa out of the

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testis.
3.​ Epididymis – it is a comma shaped, highly coiled tube.
It stores and transports sperm.Pa
Immature non-motile sperms undergo physiological maturation and capacitation
to become mature and motile sperms.
Sperms are released into vas deferens.
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4.​ Vas deferens – located on either side of the testis. It is a muscular duct. It ascends along the
testis and runs upwards around the urinary bladder and enlarge to form
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ampulla.
Sperms are stored here until ejaculation.
The last part of the vas deferens receives ducts from the seminal vesicle and prostate gland to form
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an ejaculatory duct that opens into the urethra.

The urethra originates from the urinary bladder and extends through the penis through its external
opening called the urethral meatus. As it is a common medium for transport of both semen and
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urine, urethra is called the male urino-genital tract.

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Accessory glands : secretions of these glands constitute the seminal plasma.

1.​ Seminal vesicles – they are paired, sac-like glands located on either side of the urinary
bladder. They attach with the ampulla of the vas deferens to form an
ejaculatory duct.
Secrete major part of the seminal plasma which is thick, mucoid and
alkaline in nature and composed majorly of fructose, citrate and
proteolytic enzymes.
2.​ Prostate gland – gland that surrounds the ejaculatory duct at the base of the urethra and
secretes seminal plasma that is milky and alkaline in nature and rich in
calcium and phosphate which help in sperm mobility.
 3.​ Cowper’s gland – also called the Bulbourethral gland.
Secretes seminal plasma that is mucoid in nature and helps in the
lubrication of the penis.
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External genitalia – Penis

Functions as the copulatory organ and a common passage for urine and semen.
It is made up of special tissue to help in the erection of penis to facilitate insemination.
The enlarged end of the penis is called Glans penis and is covered by a loose fold of skin called
the foreskin.
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Female Reproductive system

The human female reproductive system consists of:

a.​ The primary sex organs - Ovaries

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b.​ The accessory ducts - Fallopian tube
Uterus
​ ​ Vagina
c.​ The external genitalia - Vulva
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d.​ The mammary gland
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The Ovaries - Ovaries are the pair of primary female sex organs present on each side of the
lower abdomen in the pelvic region of the human female.
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They are almond shaped and 2-4 cm in length.

Attach to the body wall through Mesovaria and attach to the uterine wall through Ovarian
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ligament.
Ovum or egg is produced in the ovaries through the process of oogenesis.
Ovarian hormones are produced and secreted in the ovaries.
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T.S of Ovary
●​ Each ovary is covered by a tough connective tissue capsule called the tunica albuginea
which has a thin epithelial covering called the germinal epithelium that encloses the ovarian
stroma.
●​ Ovarian stroma is divided into peripheral cortex and an inner medulla.
●​ The peripheral cortex consists of the ovarian follicles in various stages of development such
as primary follicle, secondary follicle, Graafian follicle, etc.
●​ Mature mammalian egg is called Graafian follicle. The wall of Graafian follicle is made up
of outer theca externa and inner theca interna. Graafian follicle encloses a large central
cavity called antrum. At the end of the membrana granulosa is a heap of cells projecting into
the antrum called cumulus oophorus.
●​ The inner medulla consists of the blood vessels.

Fallopian tube/ Oviduct :

 ●​ A pair of 10-12 cm in length fallopian tubes that extend from the periphery of the ovary to
the uterus on each side are present.
●​ Fallopian tube is further divided into the following parts :
●​ Infundibulum - it is the part of the fallopian tube closer to the ovary that is funnel shaped.
The edges of the infundibulum possess finger-like projections called fimbriae that help in
collection of the ovum after ovulation.
●​ Ampulla - it is the dilated, wider part of the fallopian tube that is the site of fertilization.
●​ Isthmus - it is the last narrow part of the fallopian tube that forms connection with the
uterus.

Uterus :
●​ It is a single, inverted pear-shaped muscular organ of the female reproductive system.
●​ It is commonly called the Womb.
●​ It is supported by ligaments attached to the pelvic wall.
●​ It is the site for implantation of blastocyst.
●​ The walls of the uterus have three layers of tissue,
●​ Perimetrium - it is the external thin membranous layer of the uterus.

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●​ Myometrium - it is the middle thick smooth muscle layer of the uterus that undergoes
contraction during parturition.
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●​ Endometrium - it is the inner glandular layer of the uterus. Implantation of blastocyst occurs
at this layer. It also undergoes cyclical changes during the menstrual cycle.
●​ The uterus opens into the vagina through a narrow duct known as the Cervix. Cervix is a
cylindrical muscular part of the uterus. The cavity of the cervix is called the Cervical
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canal. Cervical canal along with vagina forms the birth canal.
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Vagina :
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●​ It is the copulation chamber where the insemination process occurs.

●​ Parturition of the baby occurs via vagina.
●​ It is muscular and 8 cm in length.
●​ Opens outside via vulva.
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​ Female external genitalia/ Vulva : Consists of mons pubis, labia majora, labia
minora, hymen and clitoris.
●​ Mons pubis- cushion of fat tissue covered by skin and pubic hair.
●​ Labia majora- fleshy fold of tissue extending down from mons pubis and surrounding the
vaginal opening.
●​ Labia minora - paired folds of tissues under the labia majora. Extensions of the labia minora
join to form a fold of skin covering the clitoris called the prepuce.
●​ Clitoris - tiny finger-like structure that lies at the upper junction of the labia minora above
the urethral opening. It is homologous to male penis.
●​ Hymen - a membrane that partially covers the opening of the vagina.
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Mammary gland :
●​ Mammary glands are paired structures containing glandular tissue and variable amount of
fat.
●​ Glandular tissue is divided into 15-20 mammary lobes.
●​ Mammary lobes contain clusters of cells called alveoli. The cells of alveoli secrete milk.
The milk secreted by alveoli is stored in the lumens of alveoli.
●​ Alveoli open into mammary tubules.
●​ The mammary tubules of each mammary lobe join to form a mammary duct.
●​ Many mammary ducts together join to form a Mammary ampulla that opens into a
Lactiferous duct connected to a nipple through which the milk is sucked out.
●​ A roughened pigmented skin surrounds the nipple and is called the areola. Areola contains
sebaceous glands that provide lubrication for the nipple during nursing.

Gametogenesis : The process of formation of haploid sperm in the testis of males and haploid

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ovum in the ovaries of females from their respective germ cells is
termed as gametogenesis.
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​ Spermatogenesis :
The process of formation of haploid sperm in the testis of human male from diploid spermatogonia
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that begins at puberty.
●​ Spermatogenesis occurs in the seminiferous tubules of each testis.
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●​ Each spermatogonium is diploid and contains 46 chromosomes (23 pairs). The

spermatogonia undergo mitotic division and multiply to increase in their number and grow
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in size.
●​ Among them, some of the spermatogonia called as the primary spermatocytes later
undergo meiosis.
●​ A primary spermatocyte (diploid) undergoes first meiotic division (reductional) to form two
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equal haploid cells called secondary spermatocytes.

●​ The secondary spermatocytes undergo second meiotic division (equational) to produce four
haploid spermatids. Thus, each primary spermatocyte gives rise to four haploid spermatids.
●​ Spermatids undergo cell differentiation to transform into spermatozoa through a process
called spermiogenesis. The spermatozoa then get embedded in the Sertoli cells to obtain
nutrition for their growth.
●​ The spermatozoa are then released from the seminiferous tubules by the process called
spermiation.

​ Hormonal control of spermatogenesis :

Spermatogenesis begins at the age of puberty due to the significant increase in the secretion of
Gonadotropin releasing hormone (GnRH) from the hypothalamus.
The increased levels of GnRH then stimulate the anterior Pituitary gland to secrete two
gonadotropins called Luteinising hormone and Follicle stimulating hormone.
Luteinising hormone(LH) - acts at the Leydig cells and stimulates the secretion of androgens that
in turn stimulate the process of spermatogenesis.
Follicle stimulating hormone(FSH) - acts on the Sertoli cells and stimulates the secretion of
factors that help in the process of spermiogenesis.
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●​ Spermiogenesis - the process of transformation of spermatids into fully developed sperm

cells with a head, neck middle piece and a tail.
●​ Spermiation - the process of releasing mature spermatozoa from the Sertoli cells of the
seminiferous tubules.

​ Structure of human sperm :

Sperm is a microscopic structure composed of head, neck, a middle piece and a tail.
The entire sperm is covered by a plasma membrane.
●​ Head :- contains an elongated haploid nucleus (23 chromosomes).
Anterior portion of the head is covered by a cap-like structure called as
Acrosome that contains enzymes that helps in dissolving membranes of the
ovum for fertilization.
●​ Neck :- contains two centrioles, a maximal centriole that is necessary for the first

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cleavage division of zygote and a distal centriole that is connected to the tail
filament.
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●​ Middle- piece :- possesses numerous mitochondria that provide energy for the
movement of tail which in turn facilitate sperm motility that is
important for fertilization.
●​ Tail :- helps the sperm to move in the female reproductive tract towards the female
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gamete for fertilization.
Sperms are released from the seminiferous tubules and are transported by the accessory ducts.
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Seminal plasma and sperms together form the semen.

​ Oogenesis :
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The process of formation of a mature haploid female gamete (ovum) from the diploid germ mother
cell (oogonia) in ovaries of the human female is termed as oogenesis. Oogenesis begins during the
embryonic developmental stage and occurs in three stages :
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a.​ Multiplication phase : This is the stage where in the cells undergo mitotic division.
Germinal epithelial cells undergo mitosis during the first month of
gestation of female foetus to form numerous (about a million) diploid Oogonia (germ
mother cells).
Among all the oogonia produced few of them form the primary oocytes which are the
precursors of the ovum.

b.​ Growth phase : This is the stage where in the primary oocytes grow in size and accumulate
yolk through the process of vitellogenesis.

c.​ Maturation phase : This is the stage where in the oocytes undergo meiotic division.
Primary oocytes (diploid) enter into the first meiotic division and get
arrested in the Diplotene stage of Prophase–I until puberty.
●​ Primary oocytes get surrounded by a layer of granulosa cells to form primary
follicles.
 ●​ The primary follicles are transformed into secondary follicles by the addition of
more layers of granulosa cells and a new theca.
●​ A large number of primary follicles undergo atresia and the number of primary
oocytes present in each ovary at the puberty are greatly reduced in number (about
60,000-80,000) and there are no new primary oocytes produced after birth.
●​ The secondary follicles transform into tertiary follicles by the formation of a
fluid-filled cavity called antrum that is surrounded by granulosa cells.
●​ Tertiary follicle is surrounded by inner theca interna and an outer theca externa.
●​ As the tertiary follicle continues its development, the primary oocyte completes its
Meiosis I division and forms a large-cell, the secondary oocyte (haploid) and a tiny
cell, first polar body.
●​ The secondary oocyte grows in size with a bulk of nutrient-rich cytoplasm.
●​ The tertiary follicle further transforms into a Graafian follicle (mature follicle).
●​ The secondary oocyte forms a new membrane, called zona pellucida, around it.
●​ On the 14th day of the menstrual cycle, Graafian follicle ruptures to release the
secondary oocyte in the process called as Ovulation.
●​ The secondary oocyte gets arrested in the Meiosis-II division until it is fertilized by

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the sperm.
●​ When the secondary oocyte is fertilized by the sperm, it completes the Meiotic-II
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division to form a large Ovum (haploid) and a tiny secondary polar body.

​ Menstrual cycle : The reproductive cycle in the female primates like monkeys, apes and
human beings is called as menstrual cycle.
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The cycle of events starting from one menstruation to the next menstruation constitutes one
menstrual cycle and lasts for about 28-29 days.
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●​ Menarche: The beginning of menstruation at puberty in human females.

●​ Menopause: Stoppage of menstruation and the menstrual cycle in human females at
the age of 45–50 years.
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One secondary oocyte (ovum) is released from either of the ovary in the middle of each
menstrual cycle.
Menstrual cycle occurs in four stages :
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1.​ Menstrual phase - The cycle starts with this phase and the menstrual flow
(menstruation)
lasts for 3–5 days. It occurs due to the breakdown of endometrial
lining and its blood vessels, along with the unfertilized ovum. Low
progesterone levels during this phase leads to the breakdown of the
endometrial lining of the uterus.

2.​ Follicular phase - In this phase, the primary follicles in the ovary grow and become
fully
mature Graafian follicle. Endometrium regenerates through
proliferation of its cells.
These changes in the ovary and uterus are induced by changes in the
pituitary hormones, FSH and LH and ovarian hormone, Estrogen.
Follicular stimulating hormone (FSH) stimulates the growth of
follicles. Both FSH and LH increase gradually during this phase.
 3.​ Ovulatory phase – Both FSH and LH attain their peak level on the 14th day of the
menstrual cycle. Rapid secretion of LH leading to its maximum level
during the mid-cycle is called as LH surge. LH surge induces the
rupture of Graafian follicle and thereby releasing the secondary
oocyte (ovum) and the process is called as ovulation.
Endometrial lining thickens.

4.​ Luteal phase - The ruptured Graafian follicle transforms into Corpus luteum. Corpus
luteum secretes progesterone that maintains the endometrium.
In the absence of fertilisation, corpus luteum degenerates to form corpus
albicans and this causes disintegration of the endometrium leading to
menstruation, marking a new cycle.
During pregnancy all events of the menstrual cycle stop and there is no

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Menstruation.

​ Fertilization and Implantation :

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●​ Fertilization- the process of fusion of haploid male gamete (sperm)and haploid
female gamete(ovum) to form a diploid zygote. It is also called as syngamy.
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●​ During copulation, the semen is released by the penis into the vagina and this process is
called insemination.
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●​ In human female, secondary oocyte is released by Graafian follicle and is transported to the
infundibulum through fimbriae. The secondary oocyte can only be fertilized within 24
hours of its release.
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●​ The motile sperms swim rapidly, pass through the cervix, enter into the uterus to reach the
ampulla region of the fallopian tube. Fertilization can occur only when the sperm and egg
are released simultaneously into the fallopian tube.
●​ Fertilization occurs in the ampullary junction of the fallopian tube.
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●​ Approach of sperm – around 300-400 million sperms are released into the female genital
tract during the insemination process. They move into the female genital tract with the help
of the lashing movement of the tail.
Prostaglandins and the suction movement of the uterus help the sperm movement in the
female genital tract. Prostaglandins cause contraction in vagina and uterus leading to the
movement of sperms to the uterus.
●​ Barriers to sperm- thick endometrium and acidic pH in the female reproductive tract act as a
barrier to sperm entry into the female genital tract.
Phagocytes present in the genital tract of a human female engulf sperm by identifying them
as a foreign body. Thus, only around 100 sperms reach the fallopian tube.
●​ Capacitation – sperms attain functional maturity in female genital tract in a process called as
capacitation. Glycoproteins and sterols are removed from the acrosomal membrane making
the membrane weak. Influx of calcium ions causes the sperms to become active and move
vigorously. The secretion of female genital tract removes the coating deposited on the
sperm, activating it to fertilize the egg.
●​ Penetration of the sperm into the secondary oocyte leads to the production of a fertilization
cone in secondary oocyte, into which the head and middle piece of the sperm are engulfed.

●​ The acrosome of sperm releases lysin to break into the secondary oocyte. Acrosome also
releases lytic enzymes, acrosin, hyaluronidase and neuraminidase that separates the cells
of the cumulus oophorus, corona radiata and zona pellucida respectively, thus making a
path for the entry of sperm into the ovum.
●​ Once the sperm enters, cortical granules are released between the plasma membrane and
zona pellucida of the secondary oocyte.
●​ The entry of the sperm into the secondary oocyte, the secondary oocyte undergoes
Meiosis-II to form a haploid Ovum and a secondary polar body.
●​ The male nucleus absorbs water and becomes bloated to form the male pronucleus.
●​ The female nucleus transforms into female pronucleus.
●​ The male pronucleus comes in contact with the female pronucleus, during which the nuclear
membrane ruptures and the paternal and maternal chromosomes are released into the
cytoplasm. This diploid cell is now called as the zygote.

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​ Implantation : the process of attachment of blastocyst to the endometrial wall of the
uterus.
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●​ The zygote undergoes successive mitotic division, called cleavage, as it moves through the
isthmus of fallopian tube towards the uterus. The daughter cells are called blastomeres.
●​ The first cleavage occurs about 30 hours after fertilization, resulting into 2 equal sized
blastomeres.
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●​ The second cleavage occurs about 20 hours after the first cleavage resulting in 4 equal sized
blastomeres.
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●​ As the cleavage progresses the number of blastomeres increase and at the end of cleavage it
results in a solid ball of 8-16 cells called Morula. Morula remains in the uterus for 2-3 days.
●​ Cell divisions continue in the morula and the blastomeres become arranged along the
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periphery leaving a central cavity, called blastocoel and the embryo at this stage is called a
blastocyst. It is a 32-celled embryonic stage. It has an outer layer of flattened cells called
trophoblast and inner cluster of rounded cell mass called inner cell mass.
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●​ The trophoblast layer of the blastocyst attaches to the endometrial lining of the uterus in a
process called as implantation. Inner cell mass further develops into embryo. Implantation
occurs on the seventh day of fertilization.
●​ The trophoblast cells produce proteolytic enzymes that dissolve a small area of the
endometrium forming a depression in it.
●​ The blastocyst buries itself in the depression and after the attachment, the uterine cells
rapidly divide and cover the blastocyst.

​ Pregnancy and embryonic development :

Pregnancy or gestation is the duration between conception and child birth. In humans
pregnancy lasts for 9 months and 1 week.
●​ After fertilization, finger-like projections appear on the trophoblast called chorionic
villi surrounded by the uterine tissue and maternal blood.
●​ The chorionic villi and the uterine tissue become interdigitated to form placenta, the
structural and functional unit, between the foetus and the uterine wall of the mother.
●​ Placenta performs the following functions:
 ○ It facilitates supply of oxygen and nutrients to the foetus.
○ It also helps in the removal of carbon dioxide and other excretory products from
the foetus.
○ It acts as an endocrine tissue and secretes and following hormones:
 Human chorionic gonadotropin (hCG)
 Human placental lactogen (hPL)
 Progestogens and Estrogens, these are necessary for the foetal growth and
maintenance of pregnancy.
●​ In the later phase of pregnancy, ovary secretes Relaxin.
●​ Umbilical cord, the structure that connects the placenta with the foetus, helps in
transport of substances to and from the foetus.
●​ immediately after implantation, the inner cell mass differentiates in the gastrulation
process to form three germ layers, the outer ectoderm, middle mesoderm and the
inner endoderm. These three germ layers give rise to all tissues and organs in adults.
●​ Inner cell mass contains certain cells called stem cells which have the potency to
give rise to all tissues and organs.

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​ Embryonic development : Pa
●​ After one month (4 weeks) of pregnancy, the heart is formed; the first sign of
growing foetus is the heartbeat. Head is defined with rudimentary eyes and ears. It
also contains a primitive nervous system.
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●​ By the end of second month (8 weeks), the foetus develops limbs and digits. Most
of the organs are well developed and the embryo is now referred as foetus.
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●​ By the end of third month (first trimester) most of the organ systems are formed.
●​ During the fifth month eruption of hair on the head is observed. The foetus also
shows movement.
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●​ By the end of six month (second trimester) the body is covered with fine hair,
eyelids separate and eyelashes are also formed.
●​ By the end of nine months of pregnancy, the foetus is completely developed and is
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ready for its delivery.

​ Parturition : The process of birth or delivery of a foetus.

●​ Estrogen level reaches its highest level in the maternal blood during the last week of
pregnancy that induces the formation of oxytocin receptors in the uterus.
●​ Signal for parturition originates from the fully developed foetus and placenta that
induces mild uterine contraction called foetal ejection reflex.
●​ The uterine contractions stimulate the release of oxytocin from the Pituitary gland.
●​ Release of oxytocin causes stronger uterine contractions which in turn stimulates
secretion of more oxytocin.
●​ The stimulatory reflex between the uterine contraction and oxytocin secretion
continues and result in stronger and stronger contraction of uterine muscles, leading
to the expulsion of the fully-developed foetus from the uterus through the birth
canal.
 ​ Lactation : Secretion of milk from the mammary glands.
●​ The mammary glands also undergo certain development during pregnancy under the
influence of hormones like prolactin (hPL) and progesterone.
●​ Oxytocin induces the contraction of the smooth muscles around the alveoli leading
to ejection of the milk.
●​ The milk that comes out of the mammary glands of the mother during the initial few
days of lactation, is called colostrum and is in yellow colour, containing cells from
the alveoli. It contains several antibodies needed to develop resistance in the
new-born baby. Colostrum is rich in Antibody IgA.

​ Important questions :
1.​ Draw a neat labelled diagram of human male reproductive system.

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5M
2.​ Name the hormone released by the ovary in the later phase of pregnancy. ​ 1M
3.​ Draw a neat labelled diagram of sectional view of female reproductive system.​ 5M

5.​ Draw a neat labelled diagram of human sperm.​ ​

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4.​ Explain the hormonal regulation of spermatogenesis.​ ​
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5M
5M
6.​ What is oogenesis? Explain the phases with schematic representation.​​ ​ 5M
7.​ Draw a neat labelled diagram of sectional view of seminiferous tubule.​ ​ 3M
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8.​ Differentiate between spermiogenesis, spermatogenesis and spermiation. 2M
(any two can be asked)​ ​ ​ ​ ​ ​ ​ ​
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9.​ Briefly explain the process of fertilization in humans.​ ​ ​ 3M

10.​ Explain the neuroendocrine mechanism that induces parturition.​ ​ ​ 3M
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11.​ What is spermatogenesis? Explain with schematic representation.​ ​ 5M

12.​ Draw a neat labelled diagram of​ mammary gland.​ ​ ​ ​ ​ 5M
13.​ What is menstrual cycle? Explain its phases. 5M
(Each of the phase can also be asked as a 2M question.)
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14.​ What is foetal ejection reflex?​ ​ ​ ​ ​ 1M

15.​ Define : a. Ovulation b. Implantation ​​ ​ ​ ​ ​ ​ 2M
16.​ Name the hormones released by corpus luteum, Leydig cells, ovary, placenta.​​ 2M
17.​ Write two events that’ occur in the ovary and uterus during the follicular
phase of menstrual cycle.​​ 2M
18. Name the accessory ducts of the male reproductive system.​ ​ 2M