Folliculogenesis: Ovarian Follicle Growth & Development

Folliculogenesis is the process in which a primordial follicle grows and develops into a specialized graafian follicle that is a mature follicle with

Folliculogenesis: Ovarian Follicle Growth & Development

Follicles

Hi there! Welcome to yet another educative post. Let's accelerate your mind and get started. Now that we are learning about Oogenesis, it is also very important to know folliculogenesis. So now, let we talk about what is folliculogenesis?

Folliculogenesis

Folliculogenesis is the process in which a primordial follicle grows and develops into a specialized graafian follicle that is a mature follicle with the potential to either ovulate its egg into the oviduct at mid-cycle to be fertilized or to die by atresia.

Primordial Follicle

We are very well know about that the primordial germ cells is become formed a mature egg. Primordial germ cells is to form groups of oogonia by mitotic division and differentiation, called egg nest. One lucky dominant oogonium from each egg nest differentiate into a primary oocyte. The remaining oogonia around the dominant oogonium develops follicular epithelium. The oogonia developing follicular epithelium is squamous cells (flattened) and is a single layer or unilamellar, these cells are called granulosa cells. This type of structure is called primordial follicle, whose diameter is about 30 to 40 microns.

Primary Follicle

Early Primary Follicle

Late Primary Follicle

The granulosa cells of the primordial follicles change from a squamous to a cuboidal shape. The first cuboidal cell is seen when the primordial follicle contains 8 granulosa cells, and the process is complete when the granulosa number reaches 19. This type of structure is called primary follicle, Whose diameter is about 0.1 mm (100 μm or microns). A primary follicle consists of cuboidal granulosa cells that are arranged in a single layer (or unilamellar) surrounding the primary oocyte.

FSH Receptor

The cuboidal granulosa cells begin to express FSH receptors. There is evidence in rodents, that granulosa-derived activin may play an important role in the expression of FSH receptor by autocrine/paracrine mechanisms. Research has shown, however, that the presence of FSH accelerates follicle growth in vitro. FSH induces the granulosa cells to make aromatase that converts the androgens (male hormones) made by the theca interna into estradiol (female hormone).

Zona pellucida

The secreted ZP proteins (id est ZP-1, ZP-2 and ZP-3) by primary oocyte begin to polymerize near the oocyte surface, forming an extracellular matrix coat called the zona pellucida that eventually encapsulates the egg. The importance of the zona pellucida is emphasized by the fact that the carbohydrate moiety of ZP-3 is the species-specific sperm-binding molecule. It is responsible for initiating the acrosome reaction in capacitated sperm.

Secondary Follicle

When the primary follicule develops with 2 to 10 layers of cuboidal or low columnar cells that form a stratified epithelium, it is called secondary follicle. In the secondary follicle, the primary oocyte completes its growth. When the follicle is about 0.2 mm (200 μm) in diameter, the primary oocyte has attained its maximum size and grows no more.

Theca Cell

One of the most important changes that occur in the development of a secondary follicle is the acquisition of a theca layer. This tissue, which consists of a layer of stroma-like cells around the basal lamina, subsequently differentiates into the inner theca interna and outer theca externa. Theca interna cells express receptors for luteinizing hormone (LH). Theca interna cells in growing follicles produced androgens (androstenedione, testosterone, and dihydrotestosterone) in response to LH. Theca-derived androgens are converted to estrogens (mainly estradiol) by the aromatase (CYP19A1) enzyme in granulosa cells.

Recall that the production of estrogen requires both the cells of the theca interna and granulosa cells. Estrogens, like all steroid hormones, are produced from cholesterol. Theca cells contain enzymes that catalyze the initial conversion of cholesterol into androgens. Consequently, androgens produced by theca cells diffuse into the granulosa cells which contain aromatase enzyme for estrogen synthesis.

Tertiary Follicle

When a preantral follicle completes the secondary stage in development, it contains five distinct structural units: a fully grown primary oocyte surrounded by a zona pellucida, six to ten layers of granulosa cells, a basal lamina, a theca interna, and a theca externa. The first indication of the onset of tertiary follicle development is the appearance of a cavity in the granulosa cells. In response to an intrinsic stimulus, a cavity begins to form at one pole of the primary oocyte. This process, called cavitation or beginning antrum formation, is characterized by the accumulation of fluid between the granulosa cells that in time results in the formation of an internal cavity. At completion of cavitation, the basic plan of the graafian follicle is established, and all the various cell types are in their proper position awaiting the stimuli that will shift them along paths of differentiation and proliferation. Based on evidence from polyoocyte follicles, the specification mechanism of cavitation probably is tightly regulated.

The Graafian Follicle

The graafian follicle is the stage after the first meiotic division has completed but before ovulation. Its diameter is about 18 to 23 mm at preovulatory state. The oocyte is now a 2N haploid, called secondary oocyte. The follicle is characterized by a large cavity or antrum containing a fluid called follicular fluid or liquor folliculi. The characteristic structural unit of all graafian follicle is the antrum. For this reason, the term antral follicle is used correctly as a synonym for graafian follicle. The secondary oocyte, having undergone the first meiotic division, is located eccentrically. It is surrounded by the zona pellucida and a layer of several cells known as the corona radiata.

The antral follicle's granulosa cells begin to differentiate themselves into four distinct subtypes or cell layers or domains:

The domain juxtaposed to the oocyte is the corona radiata that surrounds the zona pellucida.
The outermost domain is the membrana granulosa that's interior to the basal lamina.
The inner most domain is the periantral that's adjacent to the antrum.
The intermediate domain is the cumulus oophorus that connects the membrana and corona radiata granulosa cells together.

Each type of cell behaves differently in response to FSH. When released from the Graafian follicle and into the oviduct, the ovum will consist of three structures: secondary oocyte, zona pellucida and corona radiata.

Corpus Luteum

During ovulation, an secondary oocyte is released from a graafian or dominant follicle. After its release, the remaining cells of the granulosa and theca interna seal itself off and form what is known as the corpus luteum (plural corpora lutea). The center contains the remains of the blood clot that formed after ovulation. Surrounding the clot are glanulosa lutein cells (large luteal cells) and on the outside theca lutein cells (small luteal cells). These cells temporarily act as a endocrine gland that produces progesterone, estrogen, inhibin and to a lesser extent cholesterol.

The activity of the cells of the corpus luteum is sustained by leutenizing hormone. If the ovum is fertilized and implants in the uterine wall, human chorionic gonadotropin or hCG hormone (produced by trophoblast cells that are surrounding a growing embryo) replaces leutenizing hormone to sustain the activity of the cells in the corpus luteum.

Corpus Albicans

If fertilization does not occur, the cells of the corpus luteum remain active for roughly 11-12 days until the levels of LH fall and the corpus luteum involutes to form the corpus albicans. The secretory cells of the corpus luteum degenerate, are phagocytosed by macrophages and replaced by fibrous material.

Atretic Follicle

Each menstrual cycle, several primordial follicles are stimulated to continue development but only one follicles completes development to release an ovum. The other follicles degenerate through a process called atresia which can occur at any stage of development. During atresia, granulosa cells undergo apoptosis and are replaced by fibrous material. The oocyte degenerates and the basement that separated the oocyte from granulosa cells thickens to become the glassy membrane.

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