Granulosa Cell: Structure, Function & Diseases

Granulosa cells are epithelial cells localized in the ovarian follicle and consequently form a unit with the female oocyte. Depending on the stage of maturation of the follicle and the exact localization of the cell, they perform different functions, including the formation of estrogen precursors. The best-known disease of granulosa cell tissue is granulosa cell tumor, which requires invasive treatment.

What is a granulosa cell?

Epithelial cells are the elements of glandular and epithelial tissue. The cells are composed of an apical side and a basal side. Through the basal side, each epithelial cell is interconnected with the underlying tissue. Epithelial cells also occur in the ovarian follicle. The ovarian follicle corresponds to a unit of oocyte and surrounding follicular epithelial cells, also known as granulosa cells. Thus, the granulosa cell is a specific type of epithelial cell. Granulosa cells do not occur outside the ovarian follicle. The name of the cells is derived from the Latin “granum”, which literally means “grain”. The granulosa cells are therefore also referred to as granule cells in the literature. In the male organism, granulosa cells play no role whatsoever.

Anatomy and structure

Granulosa cells are located in the multilayer granule cell layer, the stratum granulosum, of the female ovarian follicle. They develop from follicular epithelial cells by gonadotropins during follicular maturation. Through this process, a primary follicle becomes a secondary follicle. The mature follicle form is called a tertiary follicle. At this stage, granulosa cells form the inner follicle wall layer and become the egg mound to which the egg attaches. Granulosa cells release fluid into the follicular cavity. They also surround the oocyte after follicular rupture and are then called corona radiata, which adheres to the zona pellucida. Granulosa cells remaining in the ovary are polarized to the storage of lipids in the sense of luteinization. They become the granulosalutein cells of the corpus luteum.

Function and Tasks

Granulosa cells perform different functions depending on the stage of maturation of the follicle and on their exact localization. For example, in the mature tertiary follicle, granulosa cells form the inner layer of the wall area and grow together to form the egg mound (cumulus oophorus). Later, the egg mound plays an essential role in the attachment of the oocyte. Granulosa cells also perform gland-like functions. They are responsible for the secretion of a fluid that later fills the follicular cavity. In addition to these functions, granulosa cells form a solid layer around the oocyte after follicular rupture has occurred. They thus form an envelope and in this association are also known as corona radiata. In the form of the corona radiata, the cells lie against the egg cell or, more precisely, the zona pellucida from the outside. Not all granulosa cells leave the ovary. The cells that remain in the ovary fulfill their task with the storage of lipids. This storage is also referred to as luteinization in the medical literature. In the course of luteinization, the retained granulosa cells become granulosalutein cells. This variant of cells later forms the corpus luteum or yellow body. In addition to these tasks, granulosa cells also perform functions in the context of hormone production. In this context, the cells are involved in the formation of estrogens. For this purpose, catalysis takes place in the granulosa cells, making aromatase a precursor of hormones. Since granulosa cells are a necessary part of the ovarian follicle and make up the follicle together with the oocyte and connective tissue layers, they play one of the most essential roles in ovulation. Ovulation is the release of an egg from the female ovary, including its subsequent uptake into the fallopian tube. Ovulation occurs month after month in the middle of the female cycle. The maturation of the ovarian follicle is regulated by the follicle-stimulating hormone and proceeds in several stages. The primary follicle stage is followed by the secondary and tertiary follicle stages. The Graaf follicle stage corresponds to the final stage of follicle maturation. Once the ovarian follicle has progressed to complete maturation, ovulation occurs.

Diseases

Sometimes the best known disease of the granulosa cells is granulosa cell tumor.This type of tumors are ovarian tumors that have a relatively low malignant potency. Granulosa cell tumors are among the mesenchymal or hormone-forming ovarian tumors and occur primarily at an age peak between 45 and 55 years. Of all ovarian tumors, only two percent are granulosa cell tumors. Histologic types of tumors include juvenile and adult granulosa cell tumors. Juvenile granulosa cell tumors sometimes occur in infants or children. Since the tumors, like all other tumors, correspond to a mass, nonspecific symptoms occur. These may be a feeling of pressure or fullness. Constipation or an increasing abdominal girth may also be symptomatic. Larger space-occupying lesions of the granulosa tissue may cause stylet torsion, which may result in acute abdomen. Because these are hormone-producing tumors, increased estrogen formation occurs in approximately one quarter of all cases. This increased formation of estrogens may result in glandular cystic or adenomatous hyperplasia in the endometrial region. Intermittent bleeding is a conceivable symptom at this stage. Young girls often develop pseudo-pubertas praecox as part of the manifestation. In the worst case, endometrial carcinoma develops from the granulosa cell tumor under continuous estrogen stimulation. Surgical procedures to resect the tumor are available as therapy for patients with granulosa cell tumor. The affected ovary is usually removed during the procedure. Advanced tumors are usually treated with chemotherapy.