Physiology

(10) 19/4/2018

Abdallah Riyalat & Abd AL-Rahman Salman

Female reproductive system All the ideas in slides are included & I think the sheet is enough but the exact text of them is not included. Some

information are from the book or from the internet. I hope I will cover all information & sorry for any mistake. Let’s

take a deep breath and start.

This lecture is talking about physiology of female reproductive system. Physiologically, Female reproductive

functions can be divided into two major phases:

1) Preparation of the female body for conception and pregnancy

2) The period of pregnancy itself.

We will cover part of the first phase.

First of all we have to remember briefly the anatomy of female reproductive system which is consist of ovaries,

fallopian tubes (also called uterine tubes), uterus, and vagina

also you have to know the internal structures which I will not talk about

them. You can review them from anatomy lecture.

In the intrauterine life the number of germ cells that are going to form the

ovum (a process called oogenesis**) are about 7 million cells (primordial

follicles).

By the time during fetal life, this number decreases gradually because

many of these cells die continuously (in a process called atresia).

At birth this number will be only 1-2 million cells.

From birth until puberty, some cells again will be atretic and they will

reach 400-500 thousand cells only (primary follicles). This number

represents the number of germ cells that are able to form mature ovum

during female life.

In the whole female life only 400-500 mature ovum is going to be

produced so out of the germ cells found at puberty many of them will die

again.

**Oogenesis: A developing egg (Oocyte) becomes Mature egg (Ovum)

through series of steps.

The Fundamental reproductive unit of the female is the single ovarian follicle.

It is composed of one germ cell (oocyte), surrounded by endocrine cells. These endocrine cells differ from one

stage to another. We will take about these stages of the follicle later but mainly these cells are granulosa cells &

theca cells.

Stages of oogenesis:

*All oocytes formed in females are produced during

fetal life. They degenerate with time and at birth the

ovaries contain about 2 million oocytes.

*All the oocytes go into meiotic arrest when they

reach the first meiotic division during fetal life.

*The primary oocytes remain in the prophase of the

first meiotic division until the time of puberty, when

they are gradually released to complete meiosis at

regular intervals known as the ovarian cycle.

*On the average only one oocyte matures during

each cycle, which occurs at monthly intervals, so that

the total amount of oocytes to be ovulated is about

500 oocytes in a lifetime.

*note: oogonia is a small diploid cell which on

maturation forms a primordial follicle in a female fetus

*when a female form a mature ovum there are 2

possibilities: either it will be fertilized by a sperm or if

the sperm is not present the body will get rid of it by

menstrual cycle.

*6-12 ovum per month will be produced but only one

of them will become mature (on the other hand in

male all germ cells will form mature sperms)

Female hormonal system: consists of three hormones:

1) Hypothalamic releasing hormone, gonadotropin releasing hormone GnRH

2) Anterior pituitary sex hormones, FSH and LH secreted in response to the release of GnRH from the

hypothalamus

3) Ovarian hormones, estrogen and progesterone secreted in response to pituitary hormones

*These hormones secreted at different rate during different parts of the female monthly sexual cycle. The

duration of the cycle averages 28 days. It may be as short as 20 days or as long as 45 days in some women.

* The ovarian changes that occur during the sexual cycle depend completely on secretion of FSH & LH.

*During childhood this cycle is not present because the hypothalamus does not secret GnRH for an unknown

reason

* At age 9 to 12 years secretion of these hormones leads to onset of normal monthly sexual cycles beginning

between the ages of 11 and 15 years (puberty).

*during first half of the cycle estrogen & progesterone are present but the progesterone with less amounts. On

the other hand in the second half the amount of progesterone is more than estrogen

*the amount of FSH will be more than LH except at the time of ovulation.

*in the middle (day 14) it is the time of ovulation where we have a significant increase in LH

*no LH no ovulation

*Estrogen and progesterone act as a negative feedback for the secretion of FSH & LH during most of the cycle

but at day 12-14 (at the time of ovulation) they act as a positive feedback causing increase the secretion of FSH

& LH during this period

Differences between spermatogenesis and oogenesis:

1. In females, mitotic proliferation of oogonia occurs prior to birth. In males, spermatogonia proliferate only after

puberty.

2. in females, meiotic divisions of oocyte produces only one mature ovum. In males, meiotic divisions of primary

spermatocyte produces 4 mature spermatozoa

3. In females, second meiotic division is completed only upon fertilization. In males, the products of meiosis

(spermatids) undergo substantial differentiation in the maturing process.

Ovarian cycle is a series of monthly repetitive physiological and developmental changes in the ovaries, which

prepare the ovaries for ovulation and subsequent development of a Corpus Luteum whose hormones will assist

in regulating the uterine cycle and, if the implantation of a developing embryo occurs, assist in regulating the

pregnancy.

It is regulated by FSH and LH

The changes that occur in the ovary during each cycle can be divided into three phases:

1) Follicular phase (day 1-13)

2) Ovulatory phase (day 13-15)

3) The luteal phase (day 15-28).

These phases run in parallel with the phases of the uterine cycle and together comprise the menstrual cycle.

Before the explanation of these phases, here is a general idea about what happens. Under the presence of

estrogen in the follicular phase, discharge of blood (menses) stop & the lining of the uterus become thick, Follicle

in the ovary begin to develop under the influence of many hormones. After that the mature ovum/follicle that is

produced during the follicular phase release oocyte (ovulation) while the remaining of the follicle in the ovary

called corpus luteum. Then the oocyte can live 24 hours or less without fertilization. Corpus luteum secret

progesterone that make a change in the uterus to prepare it for pregnancy if implantation doesn’t occur in

about 2 weeks the luteum degenerate and cause a drop in the level of estrogen and progesterone the uterus

shed itself (lining) by a process called menstruation

Ovarian Follicle Growth:

When a female child is born, each ovum is surrounded by a single layer of granulosa cells; and now it is called a

primordial follicle. This follicle is suspended as we said at prophase of meiosis 1. After puberty, when FSH and

LH begin to be secreted the follicles begin to grow

1- Enlargement of the ovum

2- Growth of additional layers of granulosa cells

These follicles are known as primary follicles.

*Function of granulosa cells:

1- Nourishment to the ovum

2- Secrete oocyte maturation inhibition factor that keep the ovum in suspended in its primordial state in the

prophase stage of meiotic division.

Antral and Vesicular Follicles:

Spindle cells derived from the ovary interstitium collect in several layers outside the granulosa cells, giving rise to

a second mass of cells called the theca.

1- Theca interna secrete estrogen and progesterone

2-Theca externa form vascular connective tissue capsule of the developing follicle

After that, the mass of granulosa cells secretes a follicular fluid that contains a high concentration of estrogen

causes an antrum to appear within the mass of granulosa cells as the figure below

*Until now, all growth stages from the primordial to antral follicle are caused by FSH alone.

After that greatly accelerated growth occurs and leads to larger follicles called vesicular follicles.

This accelerated growth is caused by:

1- Estrogen makes granulosa cells more sensitive to FSH

2- FSH and the estrogens promote LH receptors on the original granulosa cells

3- Estrogens & LH cause proliferation of the follicular thecal cells and increase their secretion

And now only one follicle fully matures each month, and the remainder undergo Atresia. But why??

The large amounts of estrogen from the most rapidly growing follicle act on the hypothalamus to depress further

enhancement of FSH secretionblocking further growth of the less well developed follicles

* The single follicle reaches a diameter of 1 to 1.5 centimeters at the time of ovulation and is called the mature

follicle.

*menarche: the first menstrual

period occur after the onset of

puberty

Ovulation:

Occurs 14 days after the onset of menstruation. The follicle ruptures at a point called stigma→ releasing the

secondary oocyte and corona radiata (granulosa cells surround the oocyte) into the peritoneal cavity to be taken

up by the oviduct.

The zona granulosa and thecal cells remain in the ovary. Granulosa and Theca interna cells change into lutein

cells and growth to form corpus luteum.

Now 1-Granulosa cells form progesterone and estrogen

2-Theca cells form androgen androstenedione and testosterone which are change by aromatase enzyme in the

granulosa cells to estrogen

Discharge of the ovum occur (with part of the cumulus) of the mature Graafian follicle from the surface of ovary at

the middle of the cycle (14+2 days before the subsequent menstruation).

Surge of LH Is Necessary for Ovulation. LH is necessary for final follicular growth and ovulation. Without this

hormone, even when large quantities of FSH are available, the follicle will not progress to the stage of ovulation.

The LH also has a specific effect on the granulosa and theca cells, converting them mainly to progesterone-

secreting cells more progesterone & decreased estrogen

After secretion of progesterone:

1- The theca externa begins to release proteolytic enzymes dissolution of the follicular wall swelling of the

entire follicle and degeneration of the stigma

2- Rapid growth of new blood vessels into the follicle wall with increase of prostaglandins by prostaglandin

endoperoxide synthase plasma transudation into the follicle (pseudo-inflammatory response) swelling of the

follicle follicle rupture

*This Process facilitated by intrafollicular pressure and contraction of smooth muscle in theca

* FSH (some LH) play a role by stimulating the release of plasminogen activator from granulosa cells (converts

plasminogen to plasmin)

Luteal phase:

within the next 2-3 days after expulsion of the ovum from the follicle, the remaining granulosa and theca interna

cells change rapidly into lutein cells (dependent mainly on LH). They enlarge in diameter and become filled with

lipid inclusions that give them a yellowish appearance (الجسم االصفر)

Corpus luteum is formed by:

1- The zona granulosa →granulosa lutein

2- Theca cells → theca lutein cells & some capillaries & c.t.

Both of these cells become cuboidal with central nucleus

The corpus luteum normally grows to about 1.5 centimeters in diameter, reaching this stage of development 7 to

8 days after ovulation then it begins to involute & loses its secretory function and its yellowish, lipid characteristic

about 12 days after ovulation (it’s now called corpus albicans)

A local hormone called luteinization-inhibiting factor, seems to hold the luteinization process in check until after

ovulation.

The corpus luteum secrete large amounts of both progesterone and estrogen. So if the pregnancy occur, it will

promote required progesterone until formation of the placenta

Corpus luteum life span:

-In the absence of fertilization, 14 days →apoptosis → Corpus albicans

- If pregnancy occur, chorionic gonadotropin which is secreted by the placenta, can act on the corpus luteum to

prolong its life usually maintaining it for at least the first 2 to 4 months of pregnancy. It has LH like action causing

further growth of CL and increases its hormonal production.

CL is important in the beginning of pregnancy because it support the early embryo until placenta takes over the

function of Estrogen & Progesterone production

Involution of the Corpus Luteum and Onset of the Next Ovarian Cycle:

1- Estrogen and progesterone inhibit the secretion of FSH & LH cause degeneration of CL

2- Lutein cells secrete small amount of inhibin hormone which inhibit FSH secretion cause degeneration of CL

Final involution normally occurs at the end of almost exactly 12 days of corpus luteum life (day 26). At this time

there is decrease in estrogen, progesterone & inhibin no further feedback inhibition for FSH secretion

growth of new follicles

Summary

About every 28 days, gonadotropic hormones from the anterior pituitary gland cause about 8 to 12 new follicles

to begin to grow in the ovaries. One of these follicles finally becomes “mature” and ovulates on the 14th day of

the cycle. During growth of the follicles, mainly estrogen is secreted. After ovulation, the secretory cells of the

ovulating follicle develop into a corpus luteum that secretes large quantities of both the major female hormones,

progesterone and estrogen. After another 2 weeks, the corpus luteum degenerates, whereupon the ovarian

hormones estrogen and progesterone decrease greatly and menstruation begins. A new ovarian cycle then

follows

We talked about negative & positive feedback but this is a combination of these information:

Positive feedback:

Sex hormones (Estrogen) ↑ → GnRH or LH/FSH↑ -- Estrogen peak (≥200pg/ml) → LH/FSH peak → during

ovulation only.

Negative feedback:

Sex hormones (Estrogen)↑ → GnRH or LH/FSH↓

*Follicular phase: Estrogen↑ → FSH↓

*Luteal phase: Estrogen & Progesterone↑ → LH/FSH↓ (formation of CL)

Estrogen & Progesterone↓ → LH/FSH↑ (regression of CL)

Indicators of ovulation:

1- Mid-abdominal pain (irritation of the peritoneum): follicles have some fluid inside them so when they rupture,

the fluid goes to peritoneal cavity causes some irritation & abdominal pain

2- Increase elasticity of cervical mucus

3- Cervical mucus dries in Arborizing form

4- Decrease Cornified cells in the vaginal mucosa

5- Increase Basal body temperature (increase 0.5 C)

6- Increase Urinary Estrogen, and pregnanediol or plasma progesterone level during luteal phase (day 21)

7- Absolute proof of ovulation is pregnancy

Menstrual phase: 4-7 days

Proliferative phase: growth of endometrium & the wall will significantly increase

Secretary phase: secretes after ovulation

FSH is mainly for the growing for the ovum

The lecture is DONE I hope you got benefit from this sheet and sorry for any mistake

“Woman” word consist of “wo” + “man”

What does “wo” mean??

It means World Origin

Greetings to All WOMEN…