Ovaries

The ovaries (singular in Latin: ovarium) are internal organs of the female reproductive system and the main endocrine glands where eggs (ova) form and are released and where female sex hormone synthesis occurs. Each woman has two ovaries, which are located within the true pelvis on either side of the uterus.

Ovary anatomy

Ovaries are the female gonads. They are almond-shaped paired organs, one on each side of the body. Their length is around 3 - 5 cm, width 1.5 - 3 cm, thickness 0.7 - 1.5 cm, and weight 5 - 8 grams. The ovaries are located in the lesser pelvis, almost vertically against the lateral wall of the pelvis along the sacroiliac joint, in the peritoneal cavity.

In relation to the uterus, the ovaries are located along its lateral wall in an area known as the ovarian fossa. The ovaries are connected to the uterus via the Fallopian tubes. The ovaries are somewhat white in color. Each ovary has two poles, two surfaces, and two margins.

Poles

Each ovary has a superior pole and an inferior pole. The superior pole, also called the tubal pole, is located along the infundibulum of the Fallopian tube. This pole is covered by the fimbriae of the Fallopian tube. It is attached to the suspensory ligament of the ovary.

The inferior pole is also known as the uterine pole. It is directed more inferiorly than the other pole and towards the uterus. The inferior pole is attached by the ligament of the ovary.

Surfaces

The ovary has a medial and a lateral surface. The medial surface faces the cavity of the lesser pelvis. The fimbriae of the Fallopian tubes lie along this surface. The lateral surface of each ovary is directed toward the lateral pelvic wall, which is lined by the parietal peritoneum.

Margins

Each ovary has two margins - anterior and posterior. The anterior margin of the ovary is sometimes also called the mesovarian margin. The meosvarium is a part o the broad ligament of the uterus covering the ovaries anteriorly up till the posterior part of the broad ligament. In the middle of the anterior margin is the hilum of the ovary, through which blood vessels, nerves, and lymphatic vessels enter or exit the ovary. The posterior margin of the ovary is a free border, without any connections, and is exposed to the peritoneal cavity.

Fixating structures of ovaries

The ovaries are fixated in the lesser (true) pelvis with the help of the following ligaments:

• Ligament of the ovary
• Suspensory ligament of the ovary
• Mesovarium

Ligament of ovary

The ligament of the ovary connects the inferior pole of the ovary to the cornu of the uterus, below the site where the Fallopian tube enters the uterus. The ligament lies between layers of the broad ligament of the uterus. The ligament of the ovary has the consistency of a cord.

The ligament contains connective tissue, elastic fibers, blood vessels, and smooth muscle cells. The elastic fibers and smooth muscles allow the ligament to change its length slightly. As the volume of the urinary bladder increases, the uterus is bent back; the ligament of the ovary stretches so that the ovary can stay in its location.

Suspensory ligament of ovary

The suspensory ligament of the ovary is a fold of the peritoneum laterally from the broad ligament of the uterus. The ligament stretches from the lateral wall of the pelvis to the superior pole of the ovary. Within the ligament are the following structures: ovarian artery, ovarian vein, ovary plexus (a nerve network arising from the celiac plexus).

Mesovarium

The ovaries are located in the peritoneal cavity, but the peritoneum does not cover them. The peritoneum is attached to the ovaries in the form of the mesovarium. The mesovarium is a duplication of the posterior fold of the broad ligament of the uterus. It extends from the posterior surface of the broad ligament of the uterus and attaches to the hilum of the ovary, suspending the ovary. Between its folds are nerves, blood vessels, and lymphatic vessels.

Ovary histology

The external surface of the ovary is covered by the tunica albuginea, which is made of collaenous connective tissue, and the outermost layer that is known as the germinal epithelium. The germinal epithelium a single layer of cuboid epithelial cells.

Underneath the tunica albuginea each ovary consists of two parts: cortex and medulla. The cortex is the outer and largest part of the ovary. It is the parenchyma where ovarian follicles in various differentiation stages are located surrounded by connective tissue. The ovarian medulla is the innermost part, located in the center of each ovary. It is the stroma of the ovary, containing loose connective tissue rich with blood vessels, lymphatics and nerves.

Functions of ovaries

The ovaries have two main functions: oogenesis - the differentation, maturation and release of ovocytes; and secretion of sex hormones, such as progesterone, estrogen, and also small numbers of androgens (for example, testosterone).

Ovarian follicles and oogenesis

The outer side of the ovarian cortex, beneath the tunica albuginea, is where the immature ovocytes or primary ovarian follicles are located. Every newborn female has a significant amount of these follicles, around 50 000 - 80 000, in every ovary. With every year, this number decreases, so each ovary has only about 10 000 follicles by the time a girl reaches puberty.

When girls reach sexual maturity, ovaries start to work in cycles. The average cycle is 28 days (the period between the first days of menstrual bleeding). During the reproduction period between age 13 and 50, in every cycle, only one (in rare cases, two) follicle matures and ovulation happens. Therefore, from puberty till climax, approximately 500 follicles mature. The ovaries function until about 45 - 50 years of age. As climax starts, the growth and development of ovocytes stop.

Oogenesis is the production of female gametes. Similar to spermatogenesis, oogenesis engages meiosis and produces haploid gametes. Unlike spermatogenesis, which is continuing process, oogenesis happens in a specific rhythm called the ovarian cycle. Only one functional gamete is made from the original germ cell. The other daughter cells become small polar bodies and eventually disintegrate.

Like those of the male, the female primordial germ cells arise from the embryo's yolk sac. These cells eventually differentiate into oogonia. Oogonia keep multiplying till the fifth gestation month and reach up to six to seven million, after which they stop developing with starting again shortly before birth.

Before birth, some of the oogonia transforms into primary ovocytes and continues development until meiosis I. Primary ovocytes that will not be stimulated to go through the meiosis I division are kept in small follicles called primordial follicles. The primordial follicle has a single layer of squamous follicular cells surrounding the ovocyte. Approximately three days before the menstrual period starts, the pituitary gland secrets follicle-stimulating hormone (FSH). If primary ovocytes respond to that, they will get larger, and the follicular cells will divide to produce the follicular epithelium. These new follicles are called the primary ovarian follicles.

In the primary follicles, the follicular cells differentiate into cuboidal epithelium and become stratified, and are called granulosa cells. The stroma surrounding the follicle turns into a fibrous capsule - theca folliculi - divides in theca interna and theca externa. The theca and granulosa cells together synthesize estrogens. Most primary follicles degenerate without further development, while some primary follicles continue growing in size as the granulosa cells secrete estrogen-rich fluid. The fluid eventually forms one big cavity called the antrum. At this point, follicles are known as the secondary ovarian follicles. This happens when menstruation phase ends around day 5.

Around day 10, only one follicle survives. It increases in size and bulges from the ovarian surface. This is the follicle that will ovulate. The ovocyte in this secondary follicle is connected to the follicular wall with the help of a mound of granulosa cells called cumulus oophorus. The ovocyte and the corona radiata, the inner part of the cumulus oophorus cells, are separated by a thin gel-like layer of proteins and polysaccharides - zona pellucida.

In response to stimulation by the follicle-stimulating hormone released from the anterior pituitary, the follicular cells secrete increasing amounts of estrogen as the follicles grow. The follicular cells produce estrogen from its precursor testosterone, supplied by a layer of cells immediately outside the follicle called the theca interna.

Now the primary ovocyte can complete its division through meiosis I. This division does not form two complete cells. Only one of the cells gets a significant amount of cytoplasm - the secondary ovocyte. The other smaller cell forms are called the first small polar body, which eventually fragments and disappears. The second ovocyte begins meiosis II, but it is arrested in it and is in this state unless fertilization happens.

If fertilization happens, meiosis II is completed, an ovum is formed, and a second polar body is formed. If fertilization does not occur, the ovocyte dies without finishing meiosis II.

The term ovum can be used only when the secondary ovocyte has undergone meiosis II. Meiosis II occurs when the sperm cell has penetrated the ovocyte. Only within matured ovocyte or ovum, after the second polar body has been released, the fusion of two nuclei can happen to form a zygota.

Ovulation

Ovulation is the release of an ovocyte that usually happens around the tenth to the fourteenth day of the menstrual cycle. One follicle has matured fully to become a vesicular ovarian follicle which is around 1 cm in diameter. Other secondary follicles regress during the menstrual cycle and become atretic. The vesicular ovarian follicle is so large that it forms a bulge on the surface of the ovary.

Under the stimulation of luteinizing hormone (LH) released by the anterior pituitary gland, this follicle ruptures and extrudes the secondary ovocyte, which may now be called the egg, into the peritoneal cavity near the Fallopian tube's opening in the process known as ovulation. The ovocyte is caught by the fimbriae of the Fallopian tube and it enters the fallopian tube. After ovulation, the corpus luteum forms in the ovary.

Corpus luteum

After ovulation happens, usually during the middle of the menstrual cycle, the ex-vesicular follicle's wall deflates. Blood from the blood vessels in the ruptured connective tissue enters into the center of the follicle and, together with the follicle's leftovers, forms the corpus hemorrhagicum. A blood clot develops and is absorbed, leaving only connective tissues.

After a while, corpus hemmorrhagicum changes into corpus luteum, which differentiates into an active temporary endocrine gland over a couple of days. It is called corpus luteum (meaning "yellow body") because a yellow lipid accumulates in the theca interna cells. These cells are now called lutein cells. The corpus luteum secretes progesterone that stimulates the uterus to be ready for a possible pregnancy. The corpus luteum has two types:

1. If fertilization does not happen, menstruation or fake corpus luteum develops. It functions during the second half of the ovarian cycle until the 27th day of the cycle. Afterward, it gets absorbed and replaced by connective tissue.
2. If fertilization happens, corpus luteum graviditatis or real corpus luteum develops. It is secreting progesterone very actively during the first four months of the pregnancy. After the pregnancy, it gets absorbed and replaced by scar tissue. In the scar, calcium salt can settle, forming corpus albicans that can stay in the ovary up to five years.

In both cases, the absorption leaves small scars in the ovary. Ovaries work in a cycle with 2 phases. The first phase is during the first half of the cycle and is called the follicular phase, while the second phase starts after the 14th day (ovulation) of the cycle and is called the luteal phase.

Ovarian hormones

The ovaries secrete steroid hormones - estrogen, progesterone, androgens - and peptides, such as inhibin, activin, and relaxin. Estrogen and progesterone play an essential part in keeping the uterus endometrial lining and are a part of the negative feedback regulation of pituitary hormone release. The functions of peptide hormones are not yet completely understood but some possible functions are described below.

Estrogen

The theca cells secrete androgens due to the luteinizing hormone (LH) from the pituitary gland, while the granulosa cells convert androgens into estrogens.

Estrogens affect secondary sex characteristics, bone, metabolism, and brain functions. The estrogens are needed for the development of the secondary sexual features of females. The growth of breast ducts and pigmentation of the areoles is stimulated by estrogens during puberty and pregnancy.

Estrogens also maintain the structure of the vaginal mucosa and stimulate cervical mucus production. They also take part in the development of the ovarian follicles and stimulation of endometrial cell proliferation. The effects of estrogens on the brain include increasing libido. Also, bone health depends on estrogens, especially during puberty.

Progesterone

Progesterone is secreted by the corpus luteum, namely, the lutein cells. It is the main sex hormone of pregnancy produced by corpus luteum until week eight, when the placenta takes over. Progesterone is needed for maintaining the pregnancy. Progesterone provides the right structure of the uterus for implantation of the embryo. Progesterone is also known to raise body temperature.

Androgens

Even though androgens are considered male sex hormones, they also have functions in female bodies. Androgens play a part in the production of estrogens. Aromatase, an enzyme, converts androgens into estrogens in the ovaries and in fat tissue. Androgens help the development of pubic and axillary hair, and also participate in regulating sex drive. If a woman has increase in androgen levels, it can cause virilization and menstrual cycle problems.

Ovarian peptide hormones

Inhibin and activin are created by Sertoli cells in the testis in males, while in females they are produced in the ovaries. The ovaries also secrete relaxin.

• Inhibin is a glycoprotein that can inhibit follicle-stimulating hormone. Inhibin is secreted by the granulosa and theca cells. Inhibin could also be involved in the selection of follicles. Increased inhibin levels can be seen in early menopause.
• Activin is a growth factor beta-peptide. Besides the ovaries, the endometrium produces great amounts of activin. During the menstrual cycle it allows the development of endometrium.
• Relaxin stimulates follicular development and ovocyte maturation, as well as helps the implantation of the embryo.

Menstrual cycle

The menstrual cycle can be described as hormonal and physiological changes that start with the endometrium's shedding and includes the release of the matured ovocyte from the follicle (ovulation). The menstrual cycle is the basic unit of the female reproductive time. On average, the cycle lasts 28 days. The cycle's length can vary within individuals but is usually quite regular for an individual. During puberty and the perimenopausal period, the cycle can be longer.

The two main phases in the ovarian cycle are the follicular phase and the luteal phase. In between the two phases, on day 14, ovulation occurs. At the same time, several changes happen in the uterus during three phases of the uterine cycle: menstrual phase or menses (happens during the follicular phase in the ovaries), proliferative phase, and secretory phase.

Menstrual phase

The menstrual phase (menses) is a part of the follicular phase. The menses and the follicular phase starts on day one of the menstrual cycle, when the endometrium shedding begins. The endometrium lining that was developed during the previous cycle is shedded and discharged through the vagina together with small amounts of blood. The bleeding or the menstrual phase typically lasts four to seven days. This phase may be painful, mainly because of vasospasms.

Follicular phase

The follicular phase of the ovarian cycle starts on day one of the menstrual cycle and lasts till ovulation. The ovarian follicles secrete estrogens that make the endometrium proliferate and gain an extensive blood supply. It is known as the decidualization of the endometrium. Selected follicles are maturing, so during ovulation, the ovocyte can be released. The developing follicle is secreting increased amounts of estrogen.

Ovulation

During ovulation, as mentioned before, the ovocyte is released from the ovary. Luteinizing hormone stimulates the release of prostaglandins and inflammatory cytokines that allows the rupture of the follicle and release of the ovocyte.

Luteal phase

In the luteal phase of the ovarian cycle, the primary hormone produced is progesterone. This phase follows ovulation, and corpus hemmorrhagicum and corpus lutem are formed. If fertilization happens, the corpus luteum persists and keeps secreting progesterone. If fertilization does not occur, the corpus luteum degenerates, a decrease in progesterone is seen, which causes the shedding of the endometrium and the start of menstrual bleeding, beginning a new cycle.

Neurovascular supply of ovaries

Arterial blood supply

The ovaries receive arterial blood supply mainly through two arteries - the ovarian branch of the uterine artery that goes through the mesovarium and the ovarian artery that passes within the suspensory ligament. The ovarian arteries arise from the anterolateral side of the abdominal aorta at the level of the second lumbar vertebra (L2).

The ovarian arteries are bilateral arteries below the renal arteries. They cross the ureters anteriorly and reach the ovaries through the suspensory ligament of the ovary, and enter the ovaries through their superior poles. Before reaching the ovary, each ovarian artery gives off a branch to the Fallopian tube. Afterward, the ovarian artery and its tubal branches form an anastomosis with their corresponding uterine artery branches and give off multiple small arteries that enter the ovaries.

Venous drainage

The venous drainage of the ovaries are provided by the ovarian veins that arise from the pampiniform plexus located in the mesovarium. These veins merge to form two left and two right ovarian veins. These veins also pass within the suspensory ligament of the ovary. Both veins on each side converge together and form one left and one right ovarian vein. These veins then pass superomedially, crossing the ureters along the ovarian arteries. The left ovary vein drains into the renal vein, while the right ovary vein flows into the inferior vena cava.

Innervation

The ovarian artery is innervated by postganglionic nerve fibers arising from the aortic ganglia, which are located around the initial parts of the ovarian arteries. These fibers are responsible for vasoconstriction. The aortic ganglia synapses with preganglionic fibers of the lesser splanchnic nerves.

Pelvic splanchnic nerves send preganglionic fibers to the inferior hypogastric plexus, and postganglionic fibers arising from the plexus are responsible for the parasympathetic innervation of the ovaries. These postganglionic fibers travel alongside the uterine arteries and are responsible for vasodilatation.

Lymphatic drainage

The lymphatic drainage of the ovaries occurs in three ways. One way is superiorly alongside the ovarian artery draining the lymph into the para-aortic lymph nodes. Drainage can also happen inferiorly via the inguinal canal to the medial group of the superficial inguinal nodes. The third way is through lymph vessels that pass horizontally to the other ovary, crossing the fundus of the uterus.