Folliculogenesis

What is folliculogenesis?

Folliculogenesis is the process of follicle growth and development, beginning with primordial follicles laid down during fetal life, through to the formation of a dominant follicle ready for ovulation. This includes oocyte growth, granulosa and theca cell proliferation, antrum formation, and hormonal regulation.

What is the time span of follicle and oocyte development?

Follicle and oocyte development begins before birth. Primordial germ cells divide mitotically in the fetus, before entering meiosis to form primary oocytes, which can remain arrested in meiosis I for decades (up to 52 years) until ovulation or degeneration (atresia).

What are primordial germ cells (PGCs) and where do they originate?

PGCs are the precursor cells of gametes (sperm or eggs). They originate in the yolk sac of the embryo around week 3 post-conception and migrate to the genital ridge, which later becomes the gonad.

What is the structure of a primordial follicle and its significance?

A primordial follicle consists of a primary oocyte arrested in meiosis I, surrounded by a single layer of flattened granulosa cells and an acellular basal lamina. It represents the ovarian reserve available throughout reproductive life. These are dormant until recruited to grow.

How do granulosa cells and theca cells differ in structure and function?

Granulosa cells (GCs): Arise from surrounding somatic cells, avascular, respond to FSH, produce estrogen via aromatase.

Theca cells: Form a vascularized outer layer around follicles at later stages, respond to LH, produce androgens and progesterone that GCs can convert to estrogen.

What is the zona pellucida and when does it appear?

The zona pellucida is an acellular glycoprotein layer secreted by the oocyte once follicle growth begins. It plays key roles in protection, fertilization, and pre-implantation development.

Explain meiosis in oocytes and where they are arrested.

Oogonia enter meiosis I to become primary oocytes and are arrested at prophase I until puberty and ovulation.

The primary oocyte resumes meiosis only when the follicle is selected for ovulation. It then progresses to metaphase II and arrests again until fertilized.

What is follicle arrest and why is it significant?

Arrest refers to oocytes halting development in meiosis I for years. It’s necessary to protect DNA integrity and coordinate with reproductive timing. Arrest also allows selection of oocytes for ovulation when hormonally appropriate.

What is follicle recruitment and selection?

Recruitment: Early antral follicles become responsive to rising FSH levels in the menstrual cycle.

Selection: Among recruited antral follicles, one becomes dominant (best at estrogen production and FSH uptake) and continues growth while others undergo atresia.

What are preantral and antral follicles?

Preantral (primary) follicles: No fluid-filled cavity, GCs proliferate, zona pellucida forms.

Antral (secondary) follicles: Contain an antrum (fluid-filled cavity), larger, grow under hormonal control (FSH and LH).

What hormonal feedback loops regulate folliculogenesis?

GnRH from hypothalamus → FSH and LH from anterior pituitary → estrogen and progesterone from ovaries.

Other factors:

Inhibin (from GCs) inhibits FSH.

Activin activates FSH.

AMH (Anti-Müllerian Hormone) from small follicles inhibits recruitment.

What’s the significance of the granulosa-theca cell cooperation in steroid production?

Theca cells synthesize androgens under LH.

Granulosa cells convert androgens to estrogens via aromatase under FSH.

Late-stage granulosa cells acquire LH receptors allowing them to also produce progesterone.

How is the dominant follicle able to suppress the growth of other follicles?

The dominant follicle secretes high levels of estradiol and inhibin, lowering FSH levels. Other follicles, less sensitive to low FSH, stop growing and undergo atresia.

What is follicular atresia and how common is it?

Atresia is the programmed degeneration of follicles not selected for ovulation. It affects 99.9% of follicles throughout reproductive life; only about 400–500 ovulate.

Why is ovarian angiogenesis important in folliculogenesis?

The vascular theca layer provides follicles with essential nutrients, oxygen, and hormonal signals. It supports steroidogenesis, especially during antral stages and luteinization.