Female Reproductive Cycle & Hormones

Female Reproductive Cycle Overview

• The female reproductive cycle involves the interplay of the ovulatory and menstrual cycles.
• These cycles are regulated by hormones originating from the hypothalamus.

Hypothalamus and Hormone Release

• The hypothalamus contains the pre-optic nucleus and the arcuate nucleus.
• These nuclei secrete gonadotropin-releasing hormone (GnRH).
• GnRH stimulates gonadotropes in the anterior pituitary.
• Gonadotropes secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH) into the bloodstream.
• FSH and LH act on the ovary.

Oogenesis

• At birth, females possess oogonia, which are diploid (2n) stem cells.
• Before puberty, oogonia convert into primordial follicles, which are still diploid.
• At puberty, localized androgens stimulate some primordial follicles to transform into primary follicles.

Follicle Development

• Primordial follicles are diploid and frozen in prophase I of meiosis.

Primary Follicle

• A primary follicle consists of a primary oocyte (frozen in prophase I) surrounded by a single layer of cuboidal or columnar follicle cells.
• FSH is crucial for converting a primary follicle into an early secondary follicle.
• FSH stimulates the proliferation of follicle cells into multiple layers of granulosa cells.
• FSH stimulates the oocyte to produce a glycoprotein membrane called the zona pellucida.
• Granulosa cells produce estrogen when stimulated by FSH.

Thecal Cells

• LH acts on thecal cells, converting cholesterol into androgens.
• Androgens from thecal cells move into granulosa cells.
• FSH stimulates granulosa cells to convert androgens into estrogen via aromatase enzymes.

Early Secondary Follicle

• FSH and LH stimulate the conversion of a primary follicle into an early secondary follicle.
• FSH causes the proliferation of granulosa cells, the production of estrogen, and the production of follicular fluid.
• Follicular fluid is rich in hyaluronic acid.

Late Secondary Follicle

• A late secondary follicle has more layers of granulosa cells and pockets of follicular fluid compared to an early secondary follicle.
• It is still a primary oocyte.

Graafian Follicle (Vesicular or Tertiary Follicle)

• FSH and LH continue to stimulate the proliferation of granulosa cells and the production of follicular fluid, which leads to more estrogen production.
• Pockets of follicular fluid coalesce to form a large, fluid-filled cavity called the antrum.
• The Graafian follicle is a secondary oocyte frozen in metaphase II, having undergone meiosis I.
• Granulosa cells directly surrounding the secondary oocyte are called corona radiata cells.

Follicular Phase

• The follicular phase spans from approximately days 1 to 14 of the cycle.
• This phase involves the development of a primordial follicle into a Graafian follicle.
• FSH is the primary hormone stimulating this phase, supported by LH.
• Products of the follicular phase include mitosis of granulosa cells, estrogen production, follicular fluid production, and the progression from a primary oocyte to a secondary oocyte.
• Around mid-follicular phase (days 7-9), rising estrogen levels exert negative feedback on the hypothalamus and anterior pituitary, inhibiting GnRH, FSH, and LH secretion.

LH Surge

• Late in the follicular phase (around days 13-14), high estrogen levels exert positive feedback, stimulating the hypothalamus to release more GnRH and the anterior pituitary to release a surge of LH.
• The Graafian follicle releases inhibin B, which inhibits the anterior pituitary from releasing FSH.

Ovulation

• The LH surge increases blood flow and permeability to the Graafian follicle.
• LH activates proteases (enzymes) that break down tissue around the oocyte.
• The secondary oocyte (frozen in metaphase II), along with the zona pellucida and corona radiata cells, is ejected from the Graafian follicle.
• This process is called ovulation, usually occurring around mid-cycle (days 14-15).

Ovulatory Phase

• The ovulatory phase is triggered by the LH surge.
• The fimbriae of the fallopian tubes stiffen and sweep across the ovary surface, creating fluid currents to guide the oocyte into the fallopian tube.
• The oocyte is transported to the ampulla of the fallopian tube by cilia.

Luteal Phase

• After ovulation, the ruptured Graafian follicle fills with blood and becomes the corpus hemorrhagicum.
• LH stimulates the corpus hemorrhagicum to transform into the corpus luteum.
• LH stimulates the corpus luteum to produce progesterone.
• The luteal phase typically occurs from days 15 to 28 of the cycle.
• The primary hormone involved in this phase is LH, which leads to the production of progesterone.