The ovary () is the primary sex organ in the female reproductive system. It is the gonad in females responsible for the production and development of oocytes and their release as mature egg cells. The egg cells are also known as gametes, and the process of their development is gametogenesis, known as oogenesis in the female. The ovary also produces hormones to assist in the development of the egg cells. During their development each oocyte is contained in an ovarian follicle.
Many of the structural and functional features of the human ovary are shared with other mammals and vertebrates and ovaries of some kind are found in many invertebrates. This article is primarily about the human ovary.
The paired ovaries are located one on either side of the uterus, and connect with the uterus through the fallopian tubes. They are held in place by the ovarian ligament, and the suspensory ligament of the ovary.
The ovary progresses through many stages beginning in the prenatal period through menopause.
Structure At puberty each ovary measures around 3 cm in length by 1.5 cm wide and is 1 cm thick, and sits in a depression in the lateral wall of the pelvic cavity. This depression is called the ovarian fossa and measures around 4 cm x 3 cm x 2 cm. The fossa is bounded above by the external iliac artery and vein, in front by the obliterated umbilical artery, and behind by the ureter.Daftary, Shirish; Chakravarti, Sudip (2011). Manual of Obstetrics, 3rd Edition. Elsevier. pp. 1–16. . The ovaries lie within the peritoneal cavity on either side of the uterus to which they are attached via a fibrous cord called the ovarian ligament. They are tethered to the body wall via the suspensory ligament of the ovary, which is a posterior extension of the broad ligament of the uterus. The part of the broad ligament of the uterus that suspends the ovary is known as the mesovarium.
The ovary has an inner medullary core, and an outer cortical region, and is enclosed by a capsule of dense fibrous tissue the tunica albuginea. A layer of cuboidal epithelium from the visceral peritoneum covers the ovaries as ovarian surface epithelium.
The ovarian medulla is the highly vascular stromal tissue in the center and periphery of the ovary. Its contents include blood vessels, lymphatic vessels, immune cells, and nerves.
The ovarian hilus is the hilum in the ovary, formed by the stroma and attached to the ovarian ligament where the blood vessels, lymphatic vessels and nerves enter the medulla of the ovary. It is also the main site of ovarian hilus cells also known as ovarian Leydig cells.
The ovarian cortex is an ill-defined outer region containing many primary oocytes each enclosed in an ovarian follicle. In the cortex, in the reproductive cycle following puberty, the oocytes are contained in progressive stages of follicular development.
The side of the ovary closest to the fallopian tube is connected to it by the suspensory ligament, and the other side points downwards attached to the uterus via the ovarian ligament. Other structures and tissues of the ovaries include the hilum, and the pedicle.
Microanatomy The surface of the ovaries is covered with ovarian surface epithelium, also called germinal epithelium, a membrane consisting of a lining of simple cuboidal-to-columnar shaped mesothelium.
The outer layer is the ovarian cortex, consisting of ovarian follicles and peripheral stroma in between them. Each follicle contains a primary oocyte. At various stages of folliculogenesis in the reproductive cycle the follicles may include layers of granulosa cells in the membrana granulosa, granulosa cells of the cumulus oophorus, and its inner layer of corona radiata, the zona pellucida, internal and external cell layers of the theca, and follicular fluid. The corpus luteum are the remains of the follicle after ovulation. The innermost region of the ovary is the ovarian medulla. It can be hard to distinguish between the cortex and medulla, but follicles are usually not found in the medulla.
Pre-granulosa cells also known as follicular cells are those outer squamous epithelial cells of the follicle that change to cuboidal granulosa cells, when the primordial follicles change to primary follicles.
Development
The ovaries develop in early embryogenesis from the genital ridge, following sexual differentiation. The sex of an organism is determined at the time of fertilization, but differentiation only takes place around six weeks later.
Function
At puberty, the ovary begins to secrete increasing levels of hormones. Secondary sex characteristics begin to develop in response to the hormones. The ovary changes structure and function beginning at puberty. Since the ovaries can regulate hormones, they also play an important role in pregnancy and fertility. Usually, ovulation occurs in one of the two ovaries, releasing an egg cell each menstrual cycle. When an egg cell (mature oocyte) is released from the fallopian tube, a variety of feedback mechanisms stimulate the endocrine system, which causes hormone levels to change. These feedback mechanisms are controlled by the hypothalamus and pituitary glands. Messages or signals from the hypothalamus are sent to the pituitary gland. In turn, the pituitary gland releases hormones to the ovaries. From this signaling, the ovaries release their own hormones.
Gamete production
The ovaries are the site of gametogenesis, oogenesis in the female, producing oocytes and periodically releasing an egg cell, a mature oocyte. The developing oocytes mature to egg cells in ovarian follicles. Each pre-antral follicle contains a single oocyte surrounded by granulosa cells, enclosed in a connective tissue covering called the theca. They typically develop one at a time. As they develop they fill with follicular fluid which marks the secondary oocyte stage. When the fluid fills the antrum they are known as antral follicles, or pre-ovulatory follicles.
On maturing, a surge of luteinizing hormone is secreted by the pituitary gland, which stimulates the release of the oocyte through the rupture of the follicle, a process called ovulation. The follicle remains functional and reorganizes into a corpus luteum, which secretes progesterone to prepare the uterus for an eventual implantation of the embryo.
Hormone secretion At maturity, ovaries secrete estrogen, androgen, inhibin, and progestogen. In women before menopause, 50% of testosterone is produced by the ovaries and released directly into the blood stream. The other 50% of testosterone in the bloodstream is made from the conversion of the adrenal pre-androgens (DHEA and androstenedione) to testosterone in other parts of the body. Estrogen is responsible for the appearance of secondary sex characteristics for females at puberty and for the maturation and maintenance of the reproductive organs in their mature functional state. Progesterone prepares the uterus for pregnancy and the mammary glands for lactation. Progesterone functions with estrogen by promoting menstrual cycle changes in the endometrium.
Ovarian aging
Aging leads to a constant decline in ovarian follicles marked by menopause at around the age of 52. Although about one million oocytes are present at birth, only about 500 (about 0.05%) of these ovulate. As ovarian reserve and fertility decline with age, there is also a parallel increase in pregnancy failure and meiotic errors resulting in chromosomally abnormal conceptions. The ovarian reserve and fertility perform optimally around 20–30 years of age. Around 45 years of age, the menstrual cycle begins to change and the follicle pool decreases significantly. The events that lead to ovarian aging remain unclear. The variability of aging could include environmental factors, lifestyle habits, or genetic factors.
Women with an inherited mutation in the DNA repair gene BRCA1 undergo menopause prematurely, suggesting that naturally occurring DNA damages in oocytes are repaired less efficiently in these women, and this inefficiency leads to early reproductive failure. The BRCA1 protein plays a key role in a type of DNA repair termed homologous recombinational repair, which is the only known cellular process that can accurately repair DNA double-strand breaks. Titus et al. showed that DNA double-strand breaks accumulate with age in humans and mice in primordial follicles. Primordial follicles contain oocytes that are at an intermediate (prophase I) stage of meiosis. Meiosis is the general process in eukaryotic organisms by which germ cells are formed, and it is likely an adaptation for removing DNA damage, especially double-strand breaks, from germ line DNA (see Meiosis and Origin and function of meiosis). Homologous recombinational repair is especially promoted during meiosis. Titus et al. also found that expression of 4 key genes necessary for homologous recombinational repair of DNA double-strand breaks (BRCA1, MRE11, RAD51, and ATM) declines with age in the oocytes of humans and mice. They hypothesized that DNA double-strand break repair is vital for the maintenance of oocyte reserve and that a decline in efficiency of repair with age plays a key role in ovarian aging. A study identified 290 genetic determinants of ovarian ageing, also found that DNA damage response processes are implicated, and suggests that possible effects of extending fertility in women would improve bone health, reduce risk of type 2 diabetes, and increase the risk of hormone-sensitive cancers.
A variety of testing methods can be used to determine fertility based on maternal age. Many of these tests measure levels of hormones FSH and GnrH. Methods such as measuring anti-Müllerian hormone (AMH) levels and antral follicle count (AFC) can predict ovarian aging. AMH levels serve as an indicator of ovarian aging since the quality of ovarian follicles can be determined.
Clinical significance
Ovarian diseases can be classified as endocrine disorders or as a disorders of the reproductive system. Ovarian diseases include ovarian tumors such as ovarian germ cell tumors, ovarian cancers, and different types of ovarian cyst. Other ovarian disorders include inflammation (oophoritis), diminished functional activity (hypogonadism), failure to ovulate (annovulation), and twisting (ovarian torsion), or rupture (apoplexy) of the ovary. The ovaries may be affected by the growth of endometrial-like tissue on them (endometriosis).
If the egg fails to release from the follicle in the ovary, an ovarian cyst may form. Small ovarian cysts are common in healthy women. Some women have more follicles than usual caused by a hormonal disorder (polyendocrine metabolic ovarian syndrome), which inhibits the follicles from growing normally, and this will cause cycle irregularities.
The surgical removal or one or both ovaries is called an oophorectomy.
Some types of cancer therapy can negatively impact fertility. An option to preserve this is ovarian tissue cryopreservation where some of the tissue of the ovary cortex is removed and frozen to be replaced near to the remaining tissue after therapy completion. Tissue cryopreservation is also carried out in those who wish to postpone pregnancy, or to delay menopause. Another option to safeguard the ovaries during treatment is ovarian transposition which repositions the ovaries to a safer more shielded nearby location. Both options can be performed by laparoscopy.
History Aristotle referred to ovarectomy in Historia Animalium, in sows to stimulate growth and fatness, and in female war camels to sterilize them. However, he believed that embryos are formed when the seed of a male (produced by the sperm ducts, rather than the testicles) plants into the soil of a female (probably referring to menstrual blood), and did not subscribe to the significance of gonads in heredity. He also observed that spayed females cease to go into estrus.