1.1.1.     Hormonal Regulation of spermatogenesis –

Leydig’s Interstitial Cells

Leydig cells lie between the seminiferous tubules and act as endocrine cells which produce testosterone in the presence of luteinizing hormone (LH). Testosterone is released into the blood. Leydig cells release a class of hormones called androgens (19-carbon steroids). They secrete testosterone, androstenedione and dehydroepiandrosterone (DHEA) when stimulated by the pituitary hormone luteinizing hormone (LH). LH increases cholesterol desmolase activity (an enzyme associated with the conversion of cholesterol to pregnenolone), leading to testosterone synthesis and secretion by Leydig cells. Testosterone & LH initially act during embryonic development and later at puberty age after LH secretion from anterior hypophysis (pituitary).

The testosterone secreted by these cells along with adrenal cortex initiates the maturation of sperm at puberty.

1.2.         Oogenesis

The formation of ova or egg (female gamete) is known as oogenesis. It occurs in the ovary. Development of ovary specifically governs by fox gene. In female Primordial Germ cell (PGC’s) give rise to egg or ova.

1.2.1.     Oocytogenesis:

Primordial Germ cells (PGCs) arise from posterior proximal epiblast (junction of extraembryonic ectoderm, allantois primitive streak and epiblast) through the BMP signals supply by the extraembryonic ectoderm. Wnts signalling of visceral endoderm make posterior proximal epiblast cells to become responsive (competence) to BMP signalling. Blimpl and Prdml4 genes expression get induced by BMP and both of the gene products require for survival and migration of PGCs up to the genital ridge.

Direct migration of PGCs from epiblast to hindgut (endoderm) takes place during 8th day of fertilization. Tiar protein, an RNA binding protein prevents the apoptosis of PGCs and also helps in the migration of PGCs. Migration is done with the help of fibronectin and integrin protein. Stem cell factor (SCF), c-kit protein and its ligand (KL) are essential for PGC survival and motility.

In female embryo, the gonadal ridge is the site of PGC localization, where they maintain their number through proliferation and get covered by the coelomic epithelium. Proliferating PGC when get established in the developing ovary begin to differentiate into oogonia. Oogonia are responsible for the formation of ova. In female embryo during the fetal development, primordial germ cells (PGC’s) divides mitotically to form a large number of oogonia, between 4th to 8th week of the pregnancy oogonia start to develop and reach up to 7,00,000 (7 million) by the end of 5th month.  Up to 1-2 millions oogonia get declines after 7th month or shortly after birth or at the time of birth.

Thus only 5 million oogonia left which stop dividing and now called primordial follicle and that primordial follicle get differentiated to form primary (1°) oocyte and the primary (1°) oocyte enter in a first meiotic division.


Oocytes form by oogonia, which is stem cells by nature. Oogonia which contain follicle is called primordial follicle. Primordial follicle gets differentiate into primary follicle or primary oocyte undergo meiosis I. Thus completion of oocytogenesis takes place before or shortly after birth as soon as primary oocyte forms. After puberty primary oocytes show growth by receiving the FSH.


In mammals, female gonad is called an ovary. Ovary also acts as endocrine gland release steroids, which is responsible for female secondary sexual characteristics and support the pregnancy. Germinal epithelium present as the outermost covering of ovary, beneath the germinal epithelium another layer is presently called as tunica albuginea, which is made up of connective tissue. The region of ovary under the tunica albuginea called ovarian cortex which contains fibroblasts, elastic fiber and collagen and all of them surrounded the ovarian follicles. Three major events which took place during the early stages of gonadogenesis responsible for the formation of a functional ovary: formation of follicles, differentiation of steroid-producing cells and initiation of meiosis.

 The Follicle

An ovarian follicle contains different cell types which act as a complex unit. The mature preovulatory follicle contains layers of granulosa cells. Granulosa cells surround the oocyte and granulosa cells are surrounded by the layer of theca cell, layer of theca cell near the granulosa cell called theca internal and the layer of theca cell present outer side of theca interna called theca externa. Granulosa cells are themselves containing specialized subpopulations of cells differ in their distribution of receptors and steroidogenic characteristics known as corona Radiata, cumulus cells, mural and antral granulosa cells. The cumulus cells surround the oocyte and nourish the oocyte as well contribute to the formation of the zona pellucida. Corona Radiata attached to cumulus and oocyte through gap junction forming an electrophysiological syncytium and corona Radiata maintain the close contact to oocyte through cytoplasmic extensions across the zona pellucida.

The granulosa cells which is nearby to the basement membrane (also called lamina propia present between theca and granulosa cell) are recognized as mural granulosa cells, while those nearby to the follicular antrum are known as antral granulosa cells. The basement membrane is an acellular layer contains fibronectin, laminin, proteoglycans and several types of collagen (collagen IV alpha 1 and alpha 2, reduced amounts of alpha 3-alpha 5).

The theca internal are the major source of androgens hormone. It is crucial for the final stage of development of the Graafian follicle. Follicles can be classified as primordial follicles, preantral follicles (primary and secondary follicles), antral and preovulatory follicles.

1.2.2.     Folliculogenesis

The development of ovulatory follicles throughout the reproductive life of a female at a fixed interval called folliculogenesis. The release of mature oocyte known as ovulation, ovulation take place in every 28 days.

Construction of the zona pellucida and the formation of product required for the fertilization and early embryonic development events take place during that extended phase. Follicles ultimately had two fates either ovulate as a mature oocyte or undergo atresia (atresia is known as the death of ovarian follicle), which can occur at any point during follicular development.

Primordial follicles

In newborn females small primordial follicles (fundamental developmental unit) are present and in the adult ovary, it is the prevailing follicle type. The concerned follicular epithelial cells were derived from the coelomic epithelium and when they combine with oocyte commonly known as a primordial follicle. Oocyte and follicular epithelium constitute the Primordial follicle. A single flat layer of follicular epithelium or granulosa cells or pregranulosa cell present on primordial follicle. This granulosa cells layer surround the oocyte.

Primordial follicles are positioned in the peripheral cortex of the ovary. As the follicles and oocyte start to grow, they move deeper into the cortex of the ovary.

Primary follicles

The primordial follicle increase in size proliferate. This stage is known as the primary follicle. The oocyte of the primary follicle is known as primary oocyte which enters into the first meiotic division, at this stage development of Follicular stimulating hormone (FSH receptor) also take place on primary follicle.

The primary oocyte is an arrest in the diplotene stage of prophase I. During the arrest different type of developmental changes occurs within the primary oocyte. The zona pellucida begins to form during the arrest of 1° oocyte. Oocyte not completely surrounded by the zona pellucida until the follicle reaches the late preantral stage. Groups of oocytes cyclically restart meiosis along with the onset of puberty. Thus the first part of meiosis begins in the embryo in human female and then arrest and wait for the signal to restart the meiosis, which comes at the onset of puberty roughly 12 years later. It is also a fact that some oocytes are upheld in meiotic prophase for nearly 50 years. At the time of birth, millions of primary oocytes present but only about 400 mature during a woman's reproductive life span.

Secondary Follicles

When puberty comes, the pituitary gland secretes the FSH which receives by the FSH receptor present on the primary follicle. In response to FSH the cell resume and complete the meiosis I and enter into meiosis II and the break of arrest occur and resume the meiosis takes place. At this stage 11 to 12 primary follicles are selected to further developmental process. The granulosa cells divide mitotically, the follicles are now called secondary follicles. The secondary follicles are bigger in size, has a new outer new outer layer of connective tissue, blood vessels, and theca cells. The cell work with the granulosa cells to produce estrogen. This primary follicle recruits the stroma like theca cells after oocyte signalling. The theca cells cover the granulosa outermost layer, basal lamina and differentiate the whole capsule into theca internal and theca external.

At this stage meiosis first get complete and the formation of secondary oocyte along a polar body takes place and chromosome no divide in half.

Tertiary or Antral Follicles

As the formation of antrum takes place and mark the formation of the tertiary follicle or (or late antral follicles). The antrum is a cavity in which follicular fluid get filled.

The granulosa cells first acquire the LH receptor. During the final stages of follicle maturation, the blood supply of the theca layer increases drastically.

Several follicles reach the tertiary stage at the same time, and most of these will undergo atresia.

The secondary oocyte or tertiary follicle having the largest size of the antrum and present nearby the periphery of ovary get selected to further developmental process at the seventh day of menstrual cycle and rest undergo atresia. Thus at eight days, only one secondary oocyte remain. This tertiary follicle grows further and called is Graafian follicle. The Ovulation takes place on the 14th day of the menstrual cycle. FSH stimulates the growth of a tertiary follicle, and LH stimulates the production of estrogen by granulosa and theca cells. Once the follicle is mature, it ruptures and releases the oocyte. Cells remaining in the follicle then develop into the corpus hemorrhagicum. Corpus hemorrhagium is a temporary structure, and within four days of ovulation, it is converted into corpus luteum. Progesterone is released by corpus luteum.       

The trophoblast cell of blastocyst secretes human chorionic gonadotropin (hCG) hormones.  Human chorionic gonadotropin signals the corpus luteum to relax progesterone continuously. Corpus luteum is essential for the maintenance of pregnancy. It also releases relaxin hormones. Relaxin causes softening of pubic symphysis which helps in parturition (Delivery of the child). When there is no fertilization. The corpus luteum stops releasing progesterone after 10 days and converted into corpus albicans. When the egg is fertilized and implantation of the embryo occurs.

1.2.3.     Developmental competence

Oocyte ability to produce normal, viable and fertile offspring after fertilization. During follicular development, the acquisition of developmental competence is a gradual process.

The percentage of oocytes that can develop to the blastocyst stage usually expressed the developmental competence. Developmental competence also evaluates by morphological evaluations such as the number of blastomeres or the ratio between trophectoderm cell numbers and inner cell mass.


Throughout embryonic and neonatal life apoptosis plays an important role in the massive loss of oogonia and oocytes.

The vast majority of follicular populations go through atresia rather than ovulation.

1.2.4.     Oocyte Maturation

Oocyte maturation takes place when oocyte progresses from the diplotene to the metaphase II stage and it is a complex process because nuclear maturation also takes place in this phase. The transition from the diplotene stage to metaphase is called diakinesis. In response to the ovulatory LH, surge oocyte resumes its meiosis or removal of the secondary oocyte from the follicle takes place. During diakinesis, folding of nuclear membrane get starts, the disappearance of nuclear pores occur and then the fragmentation of nuclear membrane occur before quickly disappearing to leave only small sacs with double walls and all these events are identified as germinal vesicle breakdown (GVBD), which is the first visible sign of meiotic continuation. When nucleolus comes in the contact with the cytoplasm get disappears.

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