The Ovaries

Question 1

introduction to the female reproductive system

Answer 1

female reproductive system consists of the paired ovaries and fallopian tubes, the uterus, the vagina, and the external genitalia
- this system produces the female gametes (oocytes) and provides the environment for fertilization. it holds the embryo during its complete development through the fetal stage until birth

Question 2

the ovary

Answer 2

ovaries are small, paired organs located near the lateral walls of the pelvic cavity
- they are suspended and stabilized in the pelvic cavity by the mesovarium by a pair of supporting ligaments: the ovarian ligament and the suspensory ligament

Question 3

the mesovarium

Answer 3

a division of the broad ligament, which is a fold of the peritoneum that connects the uterus to the pelvic floor and walls

Question 4

the broad ligament

Answer 4

generally, divided into three parts: the mesometrium (mesentery of the uterus), the mesovarium (mesentery of the ovary), and the mesosalpinx (mesentery of the fallopian tubes)

Question 5

ovary layers

Answer 5

the ovary consists of four layers
from superficial to deep:
germinal epithelium, the tunica albuginea, the cortex, and the medulla

Question 6

germinal epithelium

Answer 6

the ovary itself is not covered by the mesovarium, but is covered by a simple cuboidal epithelium, the germinal epithelium
- does not give rise to germ cells

Question 7

tunica albuginea

Answer 7

deep to the germinal epithelium
dense CT layer

Question 8

ovary cortex

Answer 8

forms the outer zone of the ovary and makes up most of the ovary
- consists of CT stroma and contains ovarian follicles of varying stages of development

Question 9

ovary medulla

Answer 9

occupies the centre of the ovary and is composed of loose CT which contains blood vessels, lymphatic vessels, and nerves that supply the ovary

Question 10

functions of the ovary

Answer 10

ovaries have both endocrine and exocrine functions
- endocrine function is to produce and secrete hormones (estrogen and progesterone) as well as regulating LH and FSH
- exocrine function of the ovaries is to produce female gametes or oocytes

Question 11

ovarian follicle development

Answer 11

gamete development in females occurs in specialized structures called ovarian follicles
- each ovarian follicle contains a single oocyte, surrounded by one or more layers of cells called follicular or granulosa cells

Question 12

follicular growth: early life

Answer 12

begins in early fetal life and continues until menopause
- at birth, each ovary contains about 300 000 follicles, all in the primordial stage of development
- At puberty, rising levels of FSH from the pituitary gland triggers the start of the ovarian cycle, and each month some of the primordial follicles are stimulated to undergo further development, beginning the process of follicular growth

Question 13

follicular growth: process

Answer 13

Follicular growth involves the growth of the oocyte, proliferation and changes in the follicular cells, as well as the proliferation and differentiation of the stromal fibroblasts that surround each follicle

Question 14

types of follicles

Answer 14

There are 6 key types of follicles:
1. Primordial follicles
2. Primary follicles
3. Secondary follicles
4. Mature (Graafian)
follicles
5. Corpus luteum
6. Atretic follicles

Question 15

primordial follicles

Answer 15

formed during fetal life and therefore represent the earliest stage of follicular development
- located in the superficial ovarian cortex and they consist of a primary oocyte enveloped by a single layer of flattened follicular epithelial cells resting on a thin basal lamina

Question 16

primordial follicle organelles

Answer 16

the organelles tend to be concentrated near the nucleus and include numerous mitochondria, several Golgi complexes, and extensive RER
basal lamina surrounds follicular cells, marking a clear boundary between the follicle and stroma

Question 17

primary follicles

Answer 17

at the start of puberty, a small group of primordial follicles undergo follicular growth each month
- maturation of primordial follicles is triggered by FSH release

Question 18

unilaminar primary follicles

Answer 18

as maturation progresses, the follicular cells become cuboidal in shape, and the follicle is referred to as unilaminar
- The primary follicle is unilaminar as there is only one layer of follicular cells surrounding the oocyte
The oocyte grows to about 45 micrometers in diameter, the nucleus becomes enlarged, and the Golgi complexes, RER, and mitochondria are now prominent

Question 19

primary follicles and zona pellucida

Answer 19

At this stage, a glycoprotein-rich zona pellucida begins to form between the oocyte and the follicular cells
- The zona pellucida first appears in unilaminar primary follicles. It consists of three major glycoproteins (ZP1, ZP2, and ZP3) secreted by the oocyte
- ZP3 is an important sperm receptor that binds specific proteins on the sperm surface and induces acrosomal activation

Question 20

multilaminar primary follicles

Answer 20

Unilaminar primary follicles will then develop into multilaminar primary follicles.
- Multilaminar primary follicles have multiple layers of cuboidal follicular cells (AKA granulosa cells) and a thickened zona pellucida
- The proliferation of granulosa cells is stimulated by FSH
Cells of the ovarian stroma coalesce around the follicular cells to form a layer called the theca folliculi. A distinct basal lamina separates the follicular cells from the theca folliculi

Question 21

secondary follicles

Answer 21

Contain 8-12 layers of granulosa cells, the proliferation of which is stimulated by FSH
The primary oocyte remains arrested in prophase I. now, the oocyte is surrounded by a ring of granulosa cells called the cumulus oophorus which protrudes into the antrum
- The innermost layer of cells in the cumulus oophrus is called the corona radiata

Question 22

primary oocyte at the secondary follicle stage

Answer 22

At this stage, the primary oocyte may reach up to 150 micrometers in diameter. Small cavities filled with fluid appear between granulosa cells, which will eventually coalesce to form a large cavity called the antrum
At this stage, the theca folliculi surrounding the oocyte can be divided into two distinct parts, the theca interna and the theca externa
- The theca interna is a highly vascularized layer of steroid secreting cells located immediately external to the basement membrane. This layer synthesizes and secretes androstenedione (a precursor of androgen and estrogen) which enters the granulosa cells where it is converted into estrogen
- The theca externa is a layer of external CT

Question 23

mature (Graafian) follicle

Answer 23

Mature follicles are distinguished from secondary follicles mainly by their large size where they may reach up to 2.5 cm in diameter. They are also characterized by their large antrum that makes up most of the follicle
- Graafian follicles are the last stage in development before ovulation
- Immediately preceding ovulation, the antrum increases greatly in size, and the oocyte is displaced to one side of the follicle
- The oocyte is surrounded by the corona radiata, and rests on a pedestal of granulosa cells
The cumulus oophorus containing the oocyte, corona radiata, and associated granulosa cells will then become detached from the cell wall and float freely in the antrum

Question 24

ovulation

Answer 24

Ovulation refers to the release of a mature Graafian follicle from the ovary, a process that is stimulated by hormones
- Ovulation normally occurs midway through the menstrual cycle, around the 14th day of a typical 28 day cycle
The stimulus for ovulation is a sudden rise in LH levels. The surge of LH release coincides with, and is triggered by, a peak in estrogen levels as the Graafian follicle matures

Question 25

graafian cells in menstrual cycle

Answer 25

During a typical menstrual cycle, one follicle becomes dominant and develops further than others
- The dominant follicle usually reaches the most developed stage of follicular growth and undergoes ovulation, which involves the rupture of a mature follicle and the release of the oocyte
In the hours before ovulation, the mature dominant follicle bulging against the tunica albuginea of the ovary develops a whitish or translucent ischemic area, called the stigma, in which tissue compaction has blocked blood flow
Ovulation occurs when both the germinal epithelium of the ovary and the underlying stroma that covers the stigma are made to rupture, as a result of the loss of blood supply and the thinning of the stroma

As ovulation approaches, the oocyte and adjacent follicular cells lose their connections with the follicular wall and drift free within the antrum. The distended follicular wall then ruptures, releasing the follicular contents, including the oocyte, into the peritoneal cavity
The mature ovum which is surrounded by the zona pellucida and the corona radiata is released into the peritoneal cavity near the entrance of the fallopian tube. The ovum is then swept up by finger like processes called fimbriae into the fallopian tube. The ovum is then transported by the cilia of the epithelium lining the fallopian tube. The ovum is carried towards the ampulla where the ovum may be fertilized

Under the influence of LH, the primary oocyte completes its first meiotic division, resulting in the formation of two daughter cells: the secondary oocyte and the first polar body (a very small non-viable cell containing a nucleus and a minimal amount of cytoplasm)
The newly formed secondary oocyte enters the second meiotic division and is arrested in metaphase until fertilization occurs

Question 26

corpus luteum

Answer 26

After ovulation, the granulosa cells and theca interna of the ovulated follicle reorganize to form a large temporary endocrine gland called the corpus luteum
- The corpus luteum is a yellow glandular structure that secretes progesterone, a hormone that suppresses LH
- Progesterone also stimulates the thickening of the uterine endometrium in preparation for an embryo to be implanted
The short term fate of the corpus luteum depends on whether a pregnancy occurs

Within the corpus luteum, theca interna cells are transformed into small, dark-staining theca lutein cells that continue to secrete androstenedione
- Theca lutein cells make up approximately 20% of the cell population of the corpus luteum
- They are smaller, steroid-secreting cells present around the periphery and in the infolding of the corpus luteum
Conversely, granulosa cells are transformed into large, pale-staining granulosa lutein cells that form the bulk of the corpus luteum
- Granulosa lutein cells make up 80% of the cell population of the corpus luteum
- They secrete progesterone and convert androstenedione secreted by the theca lutein cells into estrogen

Question 27

corpus luteum of pregnancy

Answer 27

If pregnancy occurs, the uterine mucosa must not be allowed to undergo menstruation because the embryo would be lost
- Progesterone and estrogen levels must be maintained at an adequate level by the corpus luteum
To prevent the drop in circulating progesterone, cells of the implanted embryo produce a glycoprotein hormone called human chorionic gonadotropin (HCG); HCG has targets and activity similar to that of LH
- HCG maintains and promotes further growth of the corpus luteum secretion of progesterone to maintain the uterine mucosa
If an embryo is not formed, the corpus luteum will degrade

This corpus luteum of pregnancy becomes very large and is maintained by HCG for 4-5 months, by which time the placenta itself produces progesterone and estrogens at levels adequate to maintain the uterine mucosa
- It then degenerates and is replaced by a large corpus albicans

Question 28

corpus albicans

Answer 28

The ovulatory LH surge causes the corpus luteum to secrete progesterone for 10-12 days
- Without further LH stimulation and in the absence of pregnancy, both major cell types of the corpus luteum cease steroid production (progesterone and estrogen) and undergo apoptosis, with regression of the tissue
- This begins roughly 12 days after ovulation
Eventually, fibroblasts invade the non-functional corpus luteum, producing dense CT scar known as the corpus albicans
Another consequence of the decreased secretion of progesterone is menstruation, the shedding of part of the uterine mucosa

Question 29

atretic follicles

Answer 29

Follicular atresia is the breakdown of ovarian follicles that do not undergo ovulation. Most ovarian follicles undergo the degenerative process called atresia, in which follicular cells and oocytes die and are disposed of by phagocytic cells

Follicles at any stage of development, including nearly mature follicles, may become atretic
- Atresia is often first recognized in the granulosa/follicular cells
- It involves apoptosis and detachment of the granulosa cells, autolysis of the oocyte, and collapse of the zona pellucida
In most follicles, the follicular cells disappear, leaving the remnants of the zona pellucida and the oocyte. The basement membrane that separated the oocyte from the granulosa cells often thickens to become the glassy membrane
- The glassy membrane will eventually collapse, giving a characteristic rubber band appearance
Out of approximately 300,000 follicles in the two ovaries at birth, only 0.1-0.2% (about 400 follicles) develop into maturity and are ovulated, the rest become atretic and die
The resulting atretic follicles are phagocytosed by macrophages