The ovarian cortex is the outer, functional layer of the ovary. This region houses a female’s lifetime supply of egg cells (oocytes), which are held in small sacs called follicles. The cortex is the site where these follicles develop, distinguishing it from the inner medulla that contains supportive blood vessels and nerves.
Anatomy of the Ovarian Cortex
The ovarian cortex lies beneath the ovary’s surface covering. It consists of connective tissue called the stroma, which supports developing follicles and contains cells that respond to hormonal signals.
Embedded in the stroma are thousands of ovarian follicles. Most are primordial follicles, which contain an immature oocyte surrounded by a single layer of flat granulosa cells. These are the dormant form of follicles.
As development begins, a primordial follicle becomes a primary follicle when the oocyte grows and its granulosa cells become cube-shaped. It then becomes a secondary follicle as the granulosa cells multiply into layers. Theca cells then form an outer layer to assist in hormone production.
Further maturation creates a tertiary follicle, identified by a fluid-filled cavity called the antrum. The oocyte is pushed to one side by this fluid. From this stage, a follicle is selected to complete maturation and release its egg during ovulation.
Oogenesis within the Ovarian Cortex
Oogenesis, the formation of egg cells, occurs in the ovarian cortex. The cortex holds the ovarian reserve, the finite pool of oocytes a female is born with. These are stored as primordial follicles that remain dormant until recruited for development.
Initial follicle activation is continuous, but later development is hormone-dependent. Follicle-stimulating hormone (FSH) promotes the growth of granulosa cells, causing follicles to enlarge. The granulosa and theca cells then produce estrogen, which prepares the uterus for pregnancy.
Over about 85 days, one follicle in a group becomes dominant while the rest degenerate through atresia. This dominant follicle, called a Graafian follicle, completes maturation just before ovulation, when the egg is released from the ovary.
Ovarian Stem Cells
Reproductive biology long held that females are born with a fixed, non-renewable number of oocytes. This has been challenged by research suggesting ovarian stem cells (OSCs) exist in the cortex. If functional in humans, these cells could generate new oocytes, a process called neo-oogenesis.
The debate is ongoing. Some studies report isolating cells from the cortex that express markers of stem and germ cells. In animal models, researchers have reported these cells can be cultured, differentiated into oocyte-like cells, and then fertilized.
The functional capacity of these cells in human ovaries is controversial, as other studies have failed to find them. The scientific community has not reached a consensus, and their therapeutic potential is not yet a clinical reality.
Clinical Relevance of the Ovarian Cortex
The ovarian cortex is central to fertility preservation due to its high concentration of primordial follicles. Patients facing treatments that can damage the ovaries, such as chemotherapy, can opt for ovarian tissue cryopreservation. This procedure involves surgically removing and freezing a piece of the cortex.
After treatment, the thawed tissue can be transplanted back into the patient. This can restore both hormone production and fertility. The American Society for Reproductive Medicine no longer considers this technique experimental as of 2019.
Research is also exploring in vitro follicle growth (IVFG), where follicles from cortical tissue are matured in a lab. This could be a safer alternative for cancer survivors by avoiding the reintroduction of malignant cells from cryopreserved tissue. This technique is complex and still under development.
The physical stiffness of the cortex also has clinical implications. This stiffness helps regulate follicle development by keeping primordial follicles dormant. Alterations in stiffness may be linked to conditions like Primary Ovarian Insufficiency (POI), where ovarian function stops prematurely.
An abnormally less rigid cortex could lead to accelerated follicle activation and depletion. In contrast, a very stiff cortex might prevent follicles from growing. This demonstrates the delicate balance required for normal ovarian function.