Folliculogenesis and stages of follicular development
The process takes place beneath the tunica albuginea (tunica albuginea) of the ovary. During each menstrual cycle, between 3 and 30 follicles enter growth, but only one reaches the dominant stage. The rest undergo degeneration, known as atresia. Follicular development goes through four main stages:
- Primordial follicle. Contains an immature oocyte in prophase of the second meiotic division. The oocyte is surrounded by a single layer of granulosa cells.
- Primary (preantral) follicle. The oocyte enlarges. Granulosa cells actively divide and become cuboidal, forming the stratum granulosum. A connective tissue sheath, the theca (theca), begins to form from the surrounding stroma.
- Secondary (antral) follicle. Granulosa cells secrete follicular fluid (liquor folliculi), which pushes the oocyte to the periphery. The cumulus oophorus (cumulus oophorus) is formed. The theca clearly divides into the theca interna (theca interna, 2–4 cell layers) and theca externa (theca externa, dense stroma).
- Mature (preovulatory) follicle. Reaches up to 20 mm in diameter. The volume of follicular fluid increases a hundredfold. The oocyte becomes covered by the zona pellucida (zona pellucida), and meiosis resumes within it.
Hormonal regulation of the follicular phase
Follicular maturation is controlled by the hypothalamic-pituitary system. Pulsatile release of gonadotropin-releasing hormone (GnRH) stimulates the secretion of FSH and LH by the anterior pituitary.
- Luteinizing hormone (LH) triggers androgen synthesis in the theca cells.
- Follicle-stimulating hormone (FSH) is responsible for follicular growth and oocyte maturation. Under its influence, androgens are aromatized into estrogens within granulosa cells. FSH also stimulates the production of inhibin and insulin-like growth factors (IGF-1 and IGF-2).
To support their own growth, granulosa cells secrete anti-Müllerian hormone. Prior to ovulation, the number of gonadotropin receptors in the theca and granulosa cells increases sharply.
Ovulation
Ovulation occurs mid-cycle, 12–24 hours after the peak estradiol surge. The estradiol peak triggers a sharp preovulatory surge in LH via a positive feedback mechanism.
Rupture of the dominant follicle wall is ensured by three parallel mechanisms:
- Decreased tensile strength: the enzymes collagenase and plasmin degrade the collagen framework of the wall.
- Decreased rigidity: tissues become more compliant due to the action of prostaglandin E2 and relaxin.
- Oocyte extrusion: prostaglandin F2a and oxytocin stimulate smooth muscle contraction, expelling the oocyte along with the cumulus oophorus into the abdominal cavity.
The process is accompanied by bleeding from ruptured capillaries surrounding the theca cells.
Luteal phase and corpus luteum
Following ovulation, LH levels decline, but the residual amount is sufficient to trigger luteinization. Capillaries rapidly sprout into the empty follicular cavity. Granulosa cells enlarge in size and accumulate lipid droplets, forming the corpus luteum (corpus luteum).
The primary function of the corpus luteum is the secretion of progesterone. If pregnancy does not occur, by days 28–30 of the cycle, progesterone, estrogen, LH, and FSH levels drop. The corpus luteum regresses, is replaced by connective tissue, and transforms into the corpus albicans (corpus albicans).
Feedback loops
The interaction between components of the reproductive system occurs via three types of feedback loops:
- "Long" loop: sex steroids act on receptors of the hypothalamic-pituitary system.
- "Short" loop: direct communication between the pituitary gland and the hypothalamus.
- "Ultrashort" loop: local regulation within the hypothalamus driven by electrical stimulation involving neurotransmitters, neuropeptides, and neuromodulators.
To memorize the stages of follicular development, use the mnemonic PPAS: Primordial, Primary (preantral), Antral (secondary), Mature (dominant).
Class and exam questions
What happens to follicles that initiate growth but fail to become dominant?
They undergo a degeneration process called atresia.
Which substances directly degrade the follicular wall during ovulation?
The wall is degraded by proteolytic enzymes—collagenase and plasmin. Prostaglandins and oxytocin merely help expel the oocyte and reduce tissue rigidity.
Where do estrogens originate during the follicular phase?
They are produced in granulosa cells via the aromatization of androgens. The androgens themselves are previously synthesized in the theca cells under the stimulating effect of LH.
What else to study on this topic
- Microscopic structure of the dominant follicle (basement membrane, zona pellucida, granulosa)
- Mechanisms of androgen aromatization into estrogens mediated by FSH
- The role of anti-Müllerian hormone, inhibin, and IGFs in folliculogenesis
- The fifth level of reproductive function regulation (receptor apparatus of target organs)
- Morphological signs of granulosa cell luteinization
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