Graafian Follicle Is the Final Stage of Follicle Development

Folliculogenesis (also called follicular development) is the process by which follicles develop and mature (see Fig. 38.3). Follicles are in one of the following physiological states: resting, growing, degenerating, or ready to ovulate. During each menstrual cycle, the ovaries produce a group of growing follicles of which most will fail to grow to maturity and will undergo follicular atresia (death) at some stage of development. However, one dominant follicle generally emerges from the cohort of developing follicles and it will ovulate, releasing a mature haploid ovum.

Primordial follicles are generally considered the non-growing resting pool of follicles, which gets progressively depleted throughout life, by the time of menopause, the ovaries are essentially devoid of all follicles. Primordial follicles are located in the ovarian cortex (peripheral regions of the ovary) beneath the tunica albuginea.

Different Stages in the Development of an Ovum and Follicle





Fetal life

Birth Puberty



Fertilization Implantation Parturition

Migration Mitosis

First meiotic division begins Arrest in prophase Growth of oocyte and follicle Follicular maturation

Resumption of meiosis Emission of first polar body Arrest in metaphase

Second meiotic division complete Emission of second polar body

Mitotic divisions Blastocyst Body Patterning

Primordial germ cells


Primary oocyte

Secondary oocyte




Primordial follicle Primary follicle

Secondary follicle

Antral follicle ♦

Graafian follicle

Corpus luteum

Corpus albicans

Progression from primordial to the next stage of follicular development, the primary stage, occurs at a relatively constant rate throughout fetal, juvenile, prepubertal, and adult life. Once primary follicles leave the resting pool, they are committed to further development or atresia. Most become atretic, and typically only one fully developed follicle will ovulate. The conversion from primordial to primary follicles is believed to be independent of pituitary gonadotropins. The exact signal that recruits a follicle from a resting to a growing pool is unknown,- it could be programmed by the cell genome or influenced by local ovarian growth regulators.

The first sign that a primordial follicle is entering the growth phase is a morphological change of the flattened pregranulosa cells into cuboidal granulosa cells. The cuboidal granulosa cells proliferate to form a single continuous layer of cells surrounding the oocyte, which has enlarged from 20 ^m in the primordial stage to 140 |xm in diameter. At this stage, a glassy membrane, the zona pellucida, surrounds the oocyte and serves as means of attachment through which the granulosa cells communicate with the oocyte. This is the primary follicular stage of development, consisting of one layer of cuboidal granulosa cells and a basement membrane.

The follicle continues to grow, mainly through proliferation of its granulosa cells, so that several layers of granulosa cells exist in the secondary follicular stage of development (see Fig. 38.4). As the secondary follicle grows deeper into the cortex, stromal cells, near the basement membrane, begin to differentiate into cell layers called theca interna and theca externa, and a blood supply with lymphatics and nerves forms within the thecal component. The granulosa layer remains avascular.

The theca interna cells become flattened, epithelioid, and steroidogenic. The granulosa cells of secondary follicles acquire receptors for FSH and start producing small amounts of estrogen. The theca externa remains fibroblastic and provides structural support to the developing follicle.

Development beyond the primary follicle is go-nadotropin-dependent, begins at puberty, and continues in a cyclic manner throughout the reproductive years. As the follicle continues to grow, theca layers expand, and fluid-filled spaces or antra begin to develop around the granulosa cells. This early antral stage of follicle development is referred to as the tertiary follicular stage (see Fig. 38.4). The critical hormone responsible for progression from the pre-antral to the antral stage is FSH. Mitosis of the granulosa cells is stimulated by FSH. As the number of granulosa cells increases, the production of estrogens, the binding capacity for FSH, the size of the follicle, and the volume of the follicular fluid all increase significantly.

As the antra increase in size, a single, large, coalesced antrum develops, pushing the oocyte to the periphery of the follicle and forming a large 2- to 2.5-cm-diameter graafian follicle (preovulatory follicle,- see Fig. 38.4). Three distinct granulosa cell compartments are evident in the graafian follicle. Granulosa cells surrounding the oocyte are cumulus granulosa cells (collectively called cumulus oophorus). Those cells lining the antral cavity are called antral granulosa cells and those attached to the basement membrane are called mural granulosa cells. Mural and antral granulosa cells are more steroidogenically active than cumulus cells.

In addition to bloodborne hormones, antral follicles have a unique microenvironment in which the follicular fluid contains different concentrations of pituitary hormones, steroids, peptides, and growth factors. Some are present in the follicular fluid at a concentration 100 to 1,000 times higher than in the circulation. Table 38.2 lists some parameters of human follicles at successive stages of development in

Primordial follicle

Primary follicle

Primordial follicle

Primary follicle

Basement membrane Oocyte

Granulosa cells

Basement membrane Granulosa cells Fully grown oocyte Zona pellucida

Secondary follicle

Basement membrane Oocyte

Granulosa cells

Basement membrane Granulosa cells Fully grown oocyte Zona pellucida

Basement membrane Granulosa cells Zona pellucida Fully grown oocyte Presumptive theca

Graafian follicle

Basement membrane Granulosa cells Zona pellucida Fully grown oocyte Presumptive theca

Secondary follicle

Graafian follicle

Cell Layers Graafian Follicle

Theca externa Basement membrane Fully grown oocyte

Multiple layers of granulosa cells Zona pellucida Antrum Theca interna

Theca interna Cumulus oophorus Zona pellucida Antrum (follicular fluid) Corona radiata Basement membrane Granulosa cells Theca externa

The developing follicle, from primordial through graafian. (Modified from Erickson GF. In: Sciarra JJ, Speroff L, eds. Reproductive Endocrinology, Infertility, and Genetics. New York: Harper & Row, 1981.)

the follicular phase. There is a 5-fold increase in follicular diameter and a 25-fold rise in the number of granulosa cells. As the follicle matures, the intrafollicular concentration of FSH does not change much, whereas that of LH increases and that of PRL declines. Of the steroids, the concentrations of estradiol and progesterone increase 20-fold, while androgen levels remain unchanged.

The follicular fluid contains other substances, including inhibin, activin, GnRH-like peptide, growth factors, opioid peptides, oxytocin, and plasminogen activator. Inhibin and activin inhibit and stimulate, respectively, the release of FSH from the anterior pituitary. Inhibin is secreted by granulosa cells. In addition to its effect on FSH secretion, inhibin also has a local effect on ovarian cells.

Different Parameters of Follicles During the First Half of the Menstrual Cycle






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  • samantha
    Does the graafian follicle have a glassy membr?
    8 years ago
  • alfredo
    How much layer of graffian follicle?
    2 years ago

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