Audio name: hhp 17c

Duration: 47 Minutes
NT10192

[00:00:46]
CLASS DISCUSSION

Female Reproductive Physiology

● While male gametogenesis is continuous after puberty, female gametogenesis is
cyclical.
○ Gametogenesis
■ It refers to the process by which germ cells mature
■ In females, it is oogenesis or the production of mature oocytes.
○ In females, this process occurs in a cyclical nature called the menstrual cycle.
■ It lasts on average 28 days, although anything between 23 days and 35
days is considered typical.
● Interactions between the hypothalamus, anterior pituitary gland, and the ovaries (the
HPG axis) will help coordinate
○ Cyclical changes in the ovaries
■ These changes are referred to as the ovarian cycle.
■ The gonads have 2 main functions
1. Gametogenesis
2. Hormone secretion
○ Estrogen
○ Progesterone
○ Testosterone
○ Inhibin
○ Cyclical changes in the uterus
■ It arises from changes in hormone secretion coming from the ovaries.
■ These processes are included within the menstrual cycle.
■ The changes that occur in the ovarian cycle and menstrual cycle are to
promote the fertilization of oocytes.
● It is also to provide an in utero environment that favors zygote
implantation in pregnancy.
Female Reproductive Tract

●
1. Fallopian Tubes/Ovary Tubes/Oviducts
■ It will lead from the ovaries to the uterus
2. Uterus
■ If fertilization occurs, the zygote can implant in the walls of the uterus.
● It will be an environment that will favor the development of a
pregnancy.
■ Endometrium
● It is an epithelial cell that lines the uterus
■ Myometrium (Myo refers to muscle)
● It is the deeper layer
● It is a region of smooth muscle that makes up the uterus.
3. Cervix
4. Vagina

Ovarian Functions
1. Oogenesis
○ It is the production of the gametes during the fetal period.
○ The primordial germ cells or the gametes will differentiate into primary oocytes.
2. Maturation of oocytes following puberty
3. Expulsion of mature oocytes from the ovary
○ This process is known as ovulation
4. Sex steroid hormones secretion
○ Estrogen
○ Progesterone
○ Testosterone
○ Inhibin
Oogenesis
● It is the production of female gametes
● Oogonia proliferate via mitosis and differentiate into primary oocytes during fetal life.
○ In males, the immature form of germ cells is called spermatogonia.
○ About 2-4 million primary oocytes will be available at birth.
● First meiotic division begins in utero but is arrested until ovulation.

●
● The first meiotic division will be completed just before ovulation
○ One daughter cell gets all of the cytoplasms
■ It is a viable cell
■ It is the secondary oocyte
○ It also leads to the creation of the first polar body
● If fertilization occurs, it will lead to the second meiotic division.
○ One of the daughter cells will receive the majority of the cytoplasm
■ It will be now referred to as a zygote
○ There is also the creation of the second polar body
○ The zygote will travel to the uterus and if the conditions are right it can implant in
the uterine wall.
● Oocyte maturation and ovulation begin at puberty and end at menopause.
○ Out of the 2-4 million oocytes that are generated during the fetal period, about
400 eggs will be ovulated throughout a woman's life.
○ The maturation of 1 primary spermatocyte leads to the formation of 4 sperm.
■ However, each oogonium only produces 1 fully mature ovum.
Ovarian Cycle
● It is a series of events associated with the maturation and the release of an egg.
1. Follicular Phase
○ It lasts approximately days 1-14 of the menstrual cycle
○ It is when a single mature follicle and secondary oocyte develop and is released.

○
2. Luteal Phase
○ It lasts from approximately days 15-28
○ This is the time period from ovulation until the degeneration of the corpus luteum.

Follicular Phase
● Oocytes exist in follicles
○ The primary oocyte is sitting in a primordial follicle
■ Primary oocytes is surrounded by a single layer of cells called granulosa
cells.
■ The granulosa cells help to support the developing oocyte and will
secrete estrogen, inhibin, and small quantities of progesterone.

○
● Some of the primordial follicles will develop into primary follicles.
○ The oocyte grows and becomes larger
○ There is a proliferation of granulosa cells and there can be multiple layers.
○ As you increase the number of granulosa cells, there will be an increase in
estrogen concentration in the blood.
○ There will be a development of a zona pellucida
■ It is an area that provides a little bit of compartmentalization between the
oocyte and the granulosa cells.
■ It enhances the sperm binding to the surface of the oocyte to favor
fertilization.
● Development of Antral Follicles
○ It is composed of a primary oocyte, multiple layers of granulosa cells, zona
pellucida, theca cells, and antrum.
■ Theca Cells
● They secrete androgens and a little bit of progesterone.
● The androgens that are produced in the theca cells can diffuse to
the granulosa cells and be converted to estrogen.
■ Aromatase
● It is an enzyme that facilitates the conversion of androgens into
estrogens.
● Granulosa cells have very high concentrations of aromatase that
is why they can manufacture estrogen that can be secreted.
■ Antrum
● It is a fluid-filled cavity
 ○
● At the start of each menstrual cycle, 10-25 of the antral follicles will begin to mature.
○ After about one week of development, all but one of the follicles will undergo
atresia (apoptosis or programmed cell death)
○ The remaining dominant follicle (Graafian follicle) will bring the oocyte to
maturation and release it.
○ The primary oocyte will undergo the first meiotic division and becomes the
secondary oocyte.

Ovulation
● Ovulation occurs around day 14 of the menstrual cycle.

○
■ The oocyte is being expelled from the ovary and it will enter the fallopian
tube and migrate towards the uterus.
● Ovulation is triggered by the surge of the luteinizing hormone
○ It will cause the dominant follicle to fuse with the ovarian wall
○ It will secrete enzymes that will help with digestion
■ The oocyte can be released from the ovary.
○ The secondary oocyte along with the granulosa cells and the zona pellucida cells
will be released and enter the fallopian tube.
 ● The 1st day of the menstrual cycle is the 1st day of bleeding and is considered as day 1.
○ Between days 1-7, multiple follicles will develop
○ Around day 7 or so, one of the follicles will become the dominant one.
○ Over the next week, the dominant follicle mature and it will be the one released
from the ovary.

Luteal Phase: Corpus Luteum

● Following ovulation, the remaining follicular cells are transformed into the corpus luteum.
○ Corpus means body and luteum refer to a yellow color.
○ The corpus lute will be converted into an endocrine structure that lasts for about
10-14 days if pregnancy does not occur.
■ If pregnancy does happen to occur, the placenta is going to secrete
hormones that will support the corpus luteum for a period of time.
○ One of the functions of the corpus luteum is to secrete hormones.
■ It will secrete estrogen, progesterone, and inhibin.

HPG Axis

●
○ The hypothalamus will secrete GnRH that acts on the anterior pituitary gland.
○ The anterior pituitary gland triggers the secretion of FSH and LH.
○ In females, the luteinizing hormone will cause actions in the theca cells.
■ Theca cells express luteinizing hormone receptors.
● Estrogen is secreted from the granulosa cells.
○ Androgens will first be produced in the theca cells and they will migrate to the
granulosa cells.
■ The granulosa cells will convert them to estrogen to be secreted into the
blood.
○ The corpus luteum is another source of estrogen secretion.
 ● Progesterone in small amounts can be secreted by the granulosa cells and theca cells.
○ However, the corpus luteum will secrete much greater quantities of progesterone.
● Inhibin is secreted from the granulosa cells and corpus luteum.

Comparison of HPG Axis Between Males and Females

● In males, the luteinizing hormone is acted upon the Leydig cells to secrete androgens
and testosterone.
● In females, the luteinizing hormone will act on the Theca cells to secrete androgens.
● In males, the follicle-stimulating hormone acts on the Sertoli cells.
● In females, the granuloma cells will influence the oocyte development
○ The granulosa cells will secrete inhibin.

Negative Feedback Inhibition

● Estrogen can feedback to both the hypothalamus to inhibit secretion of gonadotropin-
releasing hormone.
○ It can also feedback to inhibit luteinizing hormone secretion from the anterior
pituitary gland.
○ Luteinizing hormone is the stimulus for androgen secretion that will subsequently
be converted to estrogen.
■ High concentrations of estrogen should feedback and inhibit luteinizing
hormone secretion.
● Granuloma cells produce inhibin
○ Inhibin will feedback and inhibit follicle-stimulating hormones.

General Pattern of Hormone Secretion

● Luteinizing Hormone (LH)
○ At the beginning of the menstrual phase, it is quite low
○ There will be a small increase during the follicular phase
○ LH concentrations stay fairly consistent
○ Before ovulation, there will be a major spike in LH secretion
○ LH concentrations will rapidly decline at first and then slowly decline through the
rest of the luteal phase.

○
 ● Follicle-Stimulating Hormone (FSH)
○ Very low at the beginning of the menstrual cycle
○ There will be small increases during the first phase of the follicular phase
○ FSH will decrease
○ Before ovulation, there will be a spike in FSH
○ There will be a rapid return to a low level and then concentrations will slowly
decline throughout the luteal phase.
● Estrogen
○ Estrogen concentrations tend to stay low during the first part of the follicular
phase.
○ There is a big increase in estrogen, and in fact, estrogen reaches its highest
levels just before ovulation.
○ Following ovulation, estrogen concentrations will decline and then it will be
followed by a secondary increase in estrogen concentrations.
■ However, the peak values during the luteal phase will not reach the same
values as during the follicular phase.

○
● Progesterone
○ Progesterone concentrations stay fairly low during the majority of the follicular
phase.
○ They increase slightly just before ovulation
○ During the luteal phase, progesterone concentrations become very high.
○ At the end of the menstrual cycle, there is a precipitous drop in both estrogen
and progesterone.
■ It has effects to trigger menstruation.

Early Follicular Phase

● Days ~1-7
○ Luteinizing hormone will stimulate theca cell proliferation and androgen
production.
■ Androgens will be the precursors for estrogen secretion from the
granulosa cells.
○ The increase in the follicle-stimulating hormone will signal the granulosa cells to
convert androgens to estrogens and also to nourish the developing follicle.
● Why are plasma concentrations of estrogen and progesterone low during the early
 follicular phase?
○ Estrogen secretion is going to be relatively low until the granulosa cells have
enough mass to secrete more estrogen.
● What is the split in follicle-stimulating hormone triggering?
○ It is triggering the development of the follicle during the middle follicular phase at
roughly day 7or so.
■ Due to the development of the follicle and the increase in the granulosa
cells, there will be a gradual increase in progesterone secretion.

Middle Follicular Phase

● Rising estrogen levels will inhibit the secretion (but not the production) of luteinizing
hormone and follicle-stimulating hormone.
○ These are under negative feedback control
○ The anterior pituitary is still manufacturing luteinizing hormone and follicle-
stimulating hormone, but it is not releasing these hormones into the blood.
● The granulosa cells will secrete inhibin
○ Inhibin will inhibit follicle stimulating hormone.
● The decrease in follicle-stimulating hormone leads to atresia or the dying off of the
developing follicles.
○ The dominant follicle survives because it is more sensitive to the follicle-
stimulating hormone.
■ It also expresses and responds to the luteinizing hormone
○ The process of why the dominant follicle is selected to be the dominant follicle is
not well understood.
● The dominant follicle during the second half of the follicular phase begins producing
greater quantities of estrogen.
○ Estrogen concentrations are going to spike in the blood.

Late Follicular Phase

● Once a threshold level of plasma estrogen concentration is reached, the feedback
control on the anterior pituitary gland switches from negative to positive.
○ Once estrogen levels spike, it will be a positive feedback effect.
■ It will trigger the spike in both luteinizing hormone secretion and follicle-
stimulating hormone secretion from the anterior pituitary gland.
● Estrogen-mediated LH surge induces the completion of the 1st meiotic division to
secondary oocyte production.
○ This will also trigger follicle rupture and ovulation.
■ However, the damage to the follicle and granulosa cells will lead to a
decrease in estrogen just the following ovulation.
○ Luteinizing hormone will help with the conversion of the follicle to the corpus
luteum.
■ The corpus luteum will secrete high amounts of progesterone and a little
bit of estrogen.
Luteal Phase
● Following ovulation, the corpus luteum secretes progesterone, estrogen, and inhibin.
○ These will feedback to the anterior pituitary gland to reduce luteinizing hormone
and follicle-stimulating hormone release.
○ The decrease in luteinizing hormone will lead to the degradation of the corpus
luteum after about 2 weeks unless pregnancy has occurred.
○ The corpus luteum regression leads to this precipitous drop in plasma
progesterone and estrogen concentrations.
■ This will lead to the shedding of the uterine lining or the menstrual phase
of the menstrual cycle.
● Do the cyclical fluctuations in sex steroid hormone concentrations do anything else?
○ Yes, it does

Menstrual Cycle
● It refers to a series of cyclical changes in the uterine endometrium.
○ It is to prepare the uterus for implantation if fertilization occurs.
● The events of the menstrual cycle are highly influenced by the hormones secreted
during the ovarian cycle.
● The first day of the menstrual cycle is the first day of menstrual bleeding.
● 3 Phases
1. Menstrual phase
2. Proliferative phase
3. Secretory phase

Menstrual Phase
 ● It lasts for about 3-5 days
○ This corresponds with the lowest level of ovarian hormones and gonadotropin,
● Due to the regression of the corpus luteum, estrogen and progesterone concentrations
decrease.
○ Menstruation is triggered by that precipitous decrease at the end of the luteal
phase.
● During menstruation, the uterus will shed all but the deepest layers of the endometrium.
○ As the endometrium is degraded, it will detach from the uterine walls and blood
will pass out through the vagina.

Proliferative Phase
● The proliferative phase corresponds with the mid to late follicular phase.
● During this phase, estrogen stimulates
○ Endometrial growth, vascular growth, and enlargement of the glands
○ Production of progesterone receptors by endometrial cells
○ Thinning of cervical mucus to facilitate passage of sperm

Secretory Phase
● During the secretory phase, the corpus luteum is secreting high amounts of
progesterone and a little bit of estrogen.
● During the early secretory phase, progesterone is responsible for
○ Converting estrogen-primed endometrium into a secretory tissue
○ Inhibiting uterine contractions
○ Making cervical mucus relatively impenetrable to bacteria
● Decreases in estrogen and progesterone are responsible for
○ Constriction of the uterine blood vessels and there is a decrease in oxygen and
nutrient delivery.
○ The disintegration of the endometrium
○ The uterus will begin to contract
○ There will be uterine artery dilation and this contributes to the blood loss that is
associated with the menstrual phase (50-150 mL).

Hormonal Birth Control

● Daily Pills
○ Combination pills (Estrogen and Progesterone)
○ Progesterone only pills
● Injections (Depo-Provera)
○ Progestin-only that can be given either intramuscularly or subcutaneously.
○ It will help to prevent pregnancy for approximately 3 months or so.
● Mechanisms
○ It prevents ovulation and uterine changes that facilitate implantation.

● It is very common for women who are using hormonal birth control to either have very
 light menstrual cycles.
○ In the case of injections, it completely skips menstrual cycles for 3-6 months.
● Is the lack of menstrual bleeding an issue?
○ The answer is no because of the pattern of hormone secretion.

Systemic Effects of Estradiol

● Brain
○ Temperature regulation
○ Protective against dementia
○ Promotes to be physically active
● Cardiovascular System
○ Estrogen upregulates nitric oxide production (vasodilator)
○ It decreases platelet aggregation
○ It attenuates vascular smooth muscle proliferation
■ It reduces atherosclerosis and cardiovascular disease
● Liver
○ It improves cholesterol profile by increasing HDLs and decreasing LDLs
● Bone
○ It has favorable effects to maintain bone mineral density
● Estradiol has a favorable effect on the immune system.
○ That is one of the reasons why females statistically do not get sick quite as
frequently as males.
○ However, it is commonly found that for people who have an autoimmune disease
the majority of them tend to be female.

Menopause
● It is the loss of menstrual cycles for at least one year.
● The average age for menopause to begin is about 51 or so.
● Perimenopause begins approximately 4-10 years earlier
● Cause
○ Depletion of viable ovarian follicles
■ There is a decrease in estrogen and progesterone secretion.
○ There is a compensatory increase in FSH and LH secretion
● Physiological Consequences
○ Irregular periods (shorter or longer) and eventually the woman will cease to have
the menstrual cycle and will become infertile.
○ Hot flashes and night sweats
○ Sleep problems
○ Mood changes
○ Slowed metabolism and weight gain
○ Thinning hair and dry skin
○ Increased risk in cardiovascular diseases