W34 L1 - Female Reproduction

describe the ovary

• elliptical structure

• 2-4cm long

• ~7million oogonia develop into ~ 500,000 primary oocytes

• each oocyte contained in a primary follicle

  • outer layer of granulosa cells

  • develops outer layer of cells known as theca

give a brief overview of the different stages of an egg

primordial follicle - single immature egg surrounded by single layer of supporting cells; resting state which eggs are stored in ovary

primary follicle - egg that has been recruited to start growing at beginning of each monthly cycle

secondary follicle - are multiple layers of cells surrounding the egg. Also, fluid-filled spaces start to appear within these layers

what is an oocyte

an egg

what is the ovary comprised of

a thick cortex filled will follicles, a small central medulla filled with nerves and vessels

how many eggs are used each month

• ~ a couple dozen primordial follicles to become primary follicles

• they grow

• the largest and quickest developing of them become recruited into that month cycle and continue to develop

• slower ones undergo atresia and apoptosis

• ~ 6 follicles keep growing

• by the time it comes to ovulation, you have a single dominant follicle for a human that releases an egg

what does a follicle consist of

• An oocyte: The central germ cell that has the potential to be fertilized.

• Surrounding somatic cells: These cells provide nourishment, protection, and regulatory signals to the developing oocyte. These include:

  • Granulosa cells: A layer (or multiple layers as the follicle matures) of cells directly surrounding the oocyte. They play a crucial role in oocyte development and hormone production.

  • Theca cells: A layer of cells located outside the granulosa cells. They contribute to hormone production, particularly androgens, which are then converted to estrogens by the granulosa cells. derived from the same precursor cells as muscle cells so have some muscle-like characteristics

    • Theca interna: hormone secreting

    • Theca externa: muscular capsule

how is female germ cell meiosis distinct from that of males

Timing is Different:

• In females, the process starts way before birth. The early stages of meiosis begin in the ovaries of a female fetus (prenatally). However, it gets paused at a specific point (the primary oocyte stage) and doesn't continue until puberty.  

• In males, meiosis doesn't start until puberty.

Unequal Cytoplasm Division:

• When a female germ cell divides during meiosis I, it splits into two cells of very different sizes. One gets almost all the cytoplasm (the watery stuff inside the cell) and becomes the secondary oocyte (which can potentially become the egg). The other gets very little cytoplasm and is called a polar body. This polar body usually just breaks down.  

• In males, when a germ cell divides, it splits more evenly into two cells of roughly the same size.

• Meiosis II Completes Differently:

  • In females, the secondary oocyte starts meiosis II after ovulation but gets paused again! It only completes meiosis II if it gets fertilized by a sperm. If there's no sperm, it doesn't finish the process.  (entry of sperm into egg triggers egg to complete second division)

    • when meiosis II ceises, chromosomes remain linked by chiasmata

      • can be like this for 20, 30, 40 years waiting to be ovulated

      • stored with replicated DNA like this because safest way - if a bit of DNA gets damaged its got an undamaged template copy to repair it

  • In males, meiosis II goes all the way to completion, resulting in four functional sperm cells.

     

• One Functional Gamete vs. Many:

  • The end result of female meiosis (if fertilization happens) is typically one functional egg cell (ovum) and a couple of polar bodies that don't develop further. This makes sense because the egg needs to be big and have lots of nutrients to support a developing embryo.  

  • The end result of male meiosis is four functional sperm cells, which are small and mobile, designed to travel and fertilize the egg.

     

when does the egg cell become haploid

when it gets the next set of chromosomes from the sperm

• never spends extended time in haploid state

what is anisogamy

reproductive system characterized by differentially-sized male and female gametes

• most successful strategy for reproduction

what does endocrine mean

long distance signalling via the blood stream

what does paracrine mean

short range signalling - a cell talks to its neighbours

what does autocrine mean

self signalling - a cell expresses a signalling molecule and the receptor for that molecules

describe the negative feedback loop for the release of hormones

• Stimulus: Something in your body signals a need for a change.

• Hypothalamus (Integrating Center 1 - IC₁): The hypothalamus receives this signal and releases Hormone 1 (H1). In the case of the reproductive system, this H1 is Gonadotropin Releasing Hormone (GnRH). GnRH travels a short distance to the anterior pituitary.

• Anterior Pituitary (Integrating Center 2 - IC₂): The hypothalamus's hormone (H1) tells the anterior pituitary to release Hormone 2 (H2). For the gonads, these H2 hormones are Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH). FSH and LH travel in the bloodstream to the gonads.

• Endocrine Gland (Integrating Center 3 - IC₃) / Gonads: The hormones from the anterior pituitary (H2) stimulate the endocrine gland (in this example, the gonads) to release Hormone 3 (H3). These H3 hormones are sex steroids like oestrogen, progesterone (mainly in females), and testosterone (mainly in males).

• Target Tissue: Hormone 3 (H3) travels in the blood to its target tissues in the body, causing a response.

• Negative Feedback: This is the crucial part for regulation! Hormone 3 (H3) can then act as a signal to go back to the brain and tell it to slow down the release of the earlier hormones (H1 and H2). There are two main types shown:

  • Long-loop negative feedback: Hormone 3 (from the gonads) travels all the way back to the hypothalamus and/or the anterior pituitary to inhibit the release of H1 and/or H2. It's like the final product telling the factory to make less.

  • Short-loop negative feedback: Hormone 2 (from the anterior pituitary) can also go back to the hypothalamus to inhibit the release of H1. It's like a middle manager telling the boss to slow down.

what does negative feedback with a delay result in

results in a cycle

• like the menstrual cycle

what hormones do the gonads secrete

• oestrogens

• androgens

• inhibin

• activin

• follistatin

• AMH

what hormones does the planceta secrete

• CG - chorionic gonadotrophin, hCG

• PL - placental lactogen, hPL

what hormones in regards to reproduction does the anterior pituitary gland secrete

• LH

• FSH

what hormones in regards to reproduction does the hypothalamus secrete

• GnRH - gonadotrophin-releasing hormone

which hormones are glycoprotein hormones

• FSH

• LH

• Activin

• Inhibin

• AMH

• hCG

what are the glycoprotein hormones like

• large molecules

• highly charged

• very water soluble

• travel well in bloodstream due to their charge & how they interact with water

  • means they cannot cross a plasma membrane though

  • need a cell surface receptor sitting on surface of the cell able to respond to that hormone

how do FSH and LH act

they act through cell surface receptors which then send a secondary message within the cell due to their glycoprotein hormone characteristics

What is a key characteristic of "nuclear hormones," and what are some examples?

Lipid based - typically transported around body by binding to protein carriers

Non polar - dissolve easily in oils and water; dissolve across cell membrane

They can go directly into the nucleus (the control center) of a cell to tell the DNA what to do.  

(not a scientific category like steroid hormones and peptide hormones)

Think: "Nuclear" like the nucleus of a cell!

Examples:

• Steroid Hormones: These are made from cholesterol and include:

  • Estrogen  

  • Testosterone

  • Cortisol

• Thyroid Hormones: T3 and T4 (important for energy and growth).  

How they work (simplified):

1. They are usually small and can slip through the cell's outer layer.  

2. Inside, they bind with receptors.  

3. Translocate into nucleus and transcribe target genes

Endocrine Control of Ovarian Function: Follicular Phase

• Pituitary Gland: Releases FSH (Follicle-Stimulating Hormone) and LH (Luteinizing Hormone). Think of these as the main signals from the brain to the ovary.

• FSH: The main driver of the follicular phase. It tells the granulosa cells (cells surrounding the developing egg) to grow and multiply.

• Thecal Cells: Stimulated by LH, these cells produce androgens.

• Granulosa Cells: These cells have aromatase, an enzyme that helps turn androgens (hormones like testosterone, produced by the thecal cells) into oestrogen.

• Oestrogen: As the follicle grows, granulosa cells make more oestrogen. Estrogen has several important jobs:

  • It helps the follicle grow even more.

  • It starts to thicken the lining of the uterus, preparing for a possible pregnancy.

  • It sends negative feedback to the pituitary gland, which starts to lower FSH levels a bit (but not completely yet!).

• Inhibin: Produced by the granulosa cells, inhibin also sends negative feedback specifically to the pituitary gland to reduce FSH production. Think of it as a fine-tuning mechanism to control FSH.

• Androgens: Produced by thecal cells, they are the building blocks for estrogen in the granulosa cells.

• Bi-directional Signals: The ovary and the brain (pituitary) are constantly talking to each other through these hormones (positive and negative feedback).

• Germ Cell: This is the developing egg inside the follicle. While the hormones primarily act on the follicle cells, their ultimate goal is to support the egg's maturation.

Endocrine Control of Ovarian Function: Luteal Phase

• Corpus Luteum: Forms after ovulation, mainly makes progesterone.

• Progesterone: Thickens uterus for possible pregnancy.

• LH: Keeps the corpus luteum working.

• Estrogen: Also made by corpus luteum, helps progesterone.

• Negative Feedback: Progesterone and estrogen tell the pituitary gland to lower FSH and LH.

• Inhibin: From corpus luteum, specifically lowers FSH.

• No Pregnancy: Corpus luteum breaks down, progesterone and estrogen drop, leading to menstruation.

what are the two cycles

• ovarian cycle

• uterine cycle

  • concurrent with ovarian cycle

what is the ovarian cycle

made up of

• follicular phase (10-21)

• ovulation phase

• luteal phase (follicular remnants transform to corpus luteum)

what is the uterine cycle

• menses

• proliferative phase (thickening of endometrium)

• secretory phase

  • after ovulation

  • thickened endometrium converts to a secretory structure

  • corresponds to the luteal phase

  • if no pregnancy then layers of endometrium are lost

cycle graph of the cyclic hormones, ovarian cycle, and menstrual cycle

FSH and LH highest around day 14

estradiol highest few days before ovulation then big drop

progesterone highest around day 21, stays high for around a week

• estradiol high within this window, but shorter time

uterus lining thickest at concurrent time with high progesterone and estradiol levels

• corpus luteum prevalent here

describe the follicular phase

days 1-14

• cohort of 6-12 primary follicles begins to develop

• FSH stimulates development of antral follicles

• LH stimulates production of androgens in thecal cells converted to oestrogen by aromatase in follicular cells

• about day 6 one follicle becomes dominant while others undergo atresia

• late in follicular phase, oestrogen and inhibin collectively begin to repress FSH production - LH does not decline yet though

• oestrogen stimulus prompts the endometrial lining to start proliferation

• high levels of oestrogen at end of phase prepares uterus for potential pregnancy

• cervical mucus becomes thin and stringy to facilitate sperm entry

describe the ovulation phase

day 14

• oestrogen feedback at the pituitary switches direction to positive

• sudden massive surge of LH (and FSH to lesser degree)

• LH surge triggers ovulation about 16-24 hours later

• meiosis resumes and first polar body is produced

• mature follicle secretes collagenase

• egg and antral fluid are released

  • egg surrounded by granulosa cells, now called cumulus oophorus

  • cumulus-egg complex (COC) swept into fallopian tube

• thecal cells remain in the ovary and switch to producing progesterone

describe the luteal phase

day 15-18

• corpus luteum forms from thecal cells and follicular cells that are not released as cumulus cells

• produces oestrogen and progesterone to support the uterine lining until implantation

• high levels of progesterone and oestrogen repress FSH and LH at pituitary

• if there is no implanted embryo, the corpus luteum degenerates

• declining levels of progesterone and oestrogen allow FSH and LH to rise again

  • initiates next ovarian cycle

what happens at perimenopause

• too few follicles left

• FSH and LH rising

• no follicles left to respond/if they do response bc there is so few left it takes month for levels to build up until you can trigger an ovarian cycle

  • miss periods - highly irregular

• Ovaries: Less consistent egg and hormone (estrogen, progesterone) production.

• Hormones: Levels fluctuate unpredictably.

• Periods: Become irregular (length, flow, timing).

• FSH: Levels often start to go up.

• Years Before: This phase happens before menopause (no periods for 1 year).

what is the post-menopausal state like for women

• elevated LH and FSH around 60s

• low oestrogen and progesterone

• no cycles

what happens in menopause

• cessation of reproductive cycles

• depletion of follicles

• estradiol levels decrease

• LH and FSH increase (no negative feedback of estradiol)

• most symptoms result of estradiol deficiency

menopause symptoms

• hot flushes

• emotional changes/mood swings

• osteoporosis

what is used to treat menopause

• HRTs - oestrogen and progesterone

• oestrogen therapy - oestrogen alone