Female Reproduction Pre-Reading

What is the ovarian follicle?

Functional unit of the ovary

Explain the vascularisation of the ovarian follicle

(Include how nutrients and growth factors reach it)

Avascular

(Nutrients and growth factors reach oocyte by diffusion through surrounding cells)

5 stages of ovarian follicle growth

• Primordial follicle

• Primary follicle

• Pre-antral follicle

• Antral follicle

• Graafian (ovulatory) follicle

What does the primordial contain?

Primary oocyte surrounded by layer of pre-granulosa cells

What happens in the primary follicle stage?

• Enlarged oocyte

• Development of the zona pellucida

  • Glycoprotein layer

What happens in the pre-antral follicle stage?

• Multiple granulosa cell layers form

• Follicle develops receptors for FSH and LH

• Theca layers begin differentiating and secrete androgens

What happens in the antral follicle stage?

• Fluid-filled antrum develops

• Granulosa layers multiply

• Distinct theca interna and externa layers present

What is a Graafian (ovulatory) follicle?

• Fully mature follicle

• Ready for ovulation

What are the functions of the oviduct (fallopian tube)? (3)

• Ciliated epithelium moves ovum to uterus

• Ampullary region is optimal for fertilization

• Secretions nourish gametes and support capacitation

What are the functions of the uterus? (2)

• Endometrium undergoes hormonal cyclical changes for implantation and embryo nourishment

• Myometrium’s thick smooth muscle layer contracts during labour/menstruation

When are immature oocytes formed?

During foetal life

What happens to 99.9% of oocytes?

Degenerate through atresia

How many remain at different life stages? (foetus, birth, puberty, reproductive life)

• Fetus: ~8 million

• Birth: ~2 million

• Puberty: ~200,000

• Reproductive life: ~400 ovulated; rest degenerate

What are oogonia, and when do they arise?

Primordial germ cells, arising in fetal ovary at 6–8 weeks, proliferating by mitosis

When do primary oocytes form and what happens?

• At ~20 weeks gestation

• They enter meiosis I and arrest in prophase I until puberty

What happens at puberty in oogenesis?

• Each cycle, hormonal signals resume meiosis I → secondary oocyte + 1st polar body

• Secondary oocyte arrests in metaphase II until fertilisation

When does meiosis II happen, and what is produced?

• If fertilisation occurs, meiosis II occurs

• Producing ovum + 2nd polar body

Why is cytokinesis unequal in oogenesis?

To retain cytoplasm and organelles in oocyte, while polar bodies (with little cytoplasm) degenerate

What is the menstrual cycle and how long is it?

• Hormonally coordinated cycle (~28 days, range 21–35)

• Prepares system for fertilisation/implantation, regulated by hypothalamic-pituitary-ovarian axis

When is the follicular phase?

Days 1-14

What occurs in the ovary during the follicular phase? (2)

• FSH stimulates follicle growth

• Oestrogen secretion increases

What occurs in the uterus during the follicular phase?

• Days 1–5: menstruation (endometrium shed)

• Days 5–14: endometrium proliferates under oestrogen

What occurs in the oocyte during the follicular phase?

• Primary oocyte arrested until Day 13

• LH removes block at D14 → meiosis I completed → secondary oocyte + 1st polar body

What triggers ovulation at Day 14?

• LH surge → rupture of Graafian follicle, releasing oocyte into fallopian tube

When is the luteal phase?

Days 15-28

What happens in the ovary during the luteal phase?

Corpus luteum forms, producing progesterone and oestrogen

What happens in the uterus during the luteal phase?

Progesterone induces glandular secretions: glycogen, mucopolysaccharides, glycoproteins, lipids, growth factors

What happens in the oocyte during the luteal phase (if fertilised and if not fertilised)?

• If fertilised: completes meiosis II; CL maintained until placenta takes over (~12 weeks)

• If not fertilised: oocyte degenerates, CL regresses, progesterone drops, menstruation occurs

Which hormones regulate the menstrual cycle?

Hypothalamic GnRH → FSH & LH release → regulates follicle growth, ovulation, corpus luteum → estrogen & progesterone modulate endometrium & feedback

FSH functions

• Stimulates granulosa cell aromatase (androgens → oestrogens)

• Increases LH receptor expression on granulosa cells

LH functions

• Triggers ovulation (↑ prostaglandins, progesterone, enzymes → follicle rupture)

• Stimulates theca cells (androgen production → estrogens)

• Supports corpus luteum & progesterone production

• Resumption of meiosis in oocyte

• ↑ blood flow to ovary

How do LH and FSH interact to produce estrogen?

LH stimulates theca cells → cholesterol → androstenedione → transported to granulosa cells. FSH stimulates aromatase in granulosa → converts androgens → estrone → 17β-estradiol

What are the consequences of the LH surge?

• Pathway 1: ↑ Progesterone, ↓ Estradiol

• Pathway 2: Oocyte maturation (due to ↓ OMI)

• Pathway 3: Follicle wall breakdown (↑ PGF2α → ↑ collagenase)

• Pathway 4: ↑ Blood flow (↑ PGE2 → hyperemic follicle)

• Final Result: Follicle rupture, ovum release, CL formation

What are the 3 main oestrogens in females?

17β-estradiol (most abundant), estrone, estriol

What are serum levels of 17β-estradiol during the cycle?

• Day 1: 2–8 µg/100ml

• Day 14: 12–48 µg/100ml

• Day 21: 9–30 µg/100ml

What are the effects of oestrogen?

• Uterus: gland & vessel growth, ↑ progesterone receptors, ↑ contractility

• Cervical mucus: watery/alkaline → aids sperm transport

• Secondary sex traits: hair, fat, breast duct growth

• Gonadotropins: + feedback (follicular), – feedback (luteal)

• Lipids: ↑ HDL, ↓ LDL/VLDL

• Breast: duct growth

• Other: ↑ salt/water retention (via angiotensin), bone conservation

Where is progesterone synthesised?

From cholesterol in corpus luteum and placenta

Progesterone secretions rates throughout the cycle

• Follicular ~5 mg/day

• Mid-luteal ~32 mg/day

• Late pregnancy ~300 mg/day.

What are the effects of progesterone?

• Uterus: converts glands to secretory, ↓ contractility

• Cervical mucus: thick, acidic, glycogen-rich → hinders sperm, supports embryo nutrition

• Breast: areolar tissue growth

• Gonadotropins: high levels suppress LH/FSH

• Other: slight ↑ body temperature (0.2–0.5°C), ↑ respiratory rate