SERTOLI CELL: CHARACTERISTICS, HISTOLOGY AND FUNCTIONS - BIOLOGY - 2024

The Sertoli cells are a type of sustentacular cells located in the walls of the seminiferous tubules of the testes involved in spermatogenesis. Sustainability cells are cells whose main function is to provide structural support in tissues and organs.

They are cells much taller than they are wide, with a large, irregular nucleus displaced towards the base of the cell. Their formation is controlled by the SRY gene and their number remains constant throughout the life of the organism, that is, they do not present mitotic divisions.

Histological section of the testicular parenchyma of a wild boar. The number five (5) indicates the location of the Sertoli cells. Taken and edited from: User: Uwe Gille.

The functions of Sertoli cells include regulating the development and early stages of Leydig cell function, phagocytosis of residual cytoplasm during spermatogenesis, producing different hormones, and shaping the hermatotesticular barrier.

Diseases associated with Sertoli cells include Sertoli-Leydig cell tumor and Sertoli cell syndrome or germinal aplasia.

History

Sertoli cells were discovered by the Italian physiologist Enrique Sertoli in 1865. Sertoli, who worked with various topics in human physiology, including the mechanisms of smooth muscle contraction, tissue carbonic acid and cellular proteins, discovered these cells by studying physiology. testicular.

They were named as Sertoli cells for the first time by the Viennese histologist von Ebner, twenty years after their discovery. Until the middle of the last century, these cells received little attention, as evidenced by the fact that only about 25 papers related to them were published to date.

However, with the invention of the electron microscope and the development of new study techniques in biochemistry and molecular biology, the interest in Sertoli cells increased exponentially, with about 500 investigations a year currently.

characteristics

Sertoli cells are columnar cells much taller than they are wide, displaying branched cytoplasmic processes to support developing germ cells. The highest concentration of cellular organelles is distributed towards the basal portion of the cell.

The cell nucleus is large and euchromatic, its shape is modified throughout the seminiferous epithelium cycle, occasionally presenting deep invaginations of the nuclear membrane. Its location is generally close to the base of the cell, however, it can occasionally move towards the lumen of the seminiferous tube.

The nucleolus is also very large and is intensely stained with vital dyes. Generally, this nucleolus has three clearly differentiable regions, that is, it is tripartite.

Histology

The total number of Sertoli cells will determine the maximum amount of sperm that a testicle can produce. The total volume of these cells in an individual is highly variable depending on the species, ranging from 2000 to 7000 µm³.

However, there appears to be an inverse relationship between total volume and spermatogenic efficiency. These tubular-shaped cells extend from the basement membrane into the seminiferous epithelium lumen and have a “nurse-like” function on developing germ cells.

To perform this function, Sertoli cells extend their cytoplasm in projections in the form of slender arms and a cylindrical process which surround the spermatids and form complex specialized junctions that work as gap and tight junctions. They also employ actin filaments and smooth endoplasmic reticulum.

The nucleus and nucleolus

The nucleus of the Sertoli cell is located, in most species, close to the basement membrane. It is large, elongated and occasionally its shape and location can be altered depending on the stage of the seminiferous cycle.

In the adult, the nucleus has deep invaginations of its membrane that give it an irregular shape and is surrounded by intermediate vimentin filaments. Additionally, it has a high density of pores in its membrane. Some proteins can be present in high concentrations near the areas of invagination.

The nucleolus is large and in many species it is made up of three easily distinguishable parts. It has from one to ten chrome centers.

Cytoplasm

The cytoplasm has numerous organelles that are arranged in a polarized manner, that is, there is a higher concentration of organelles towards the basal portion of the cell than towards the distal portion.

Mitochondria are very abundant and can be elongated (2–3 µm), cup-shaped, or even donut-shaped. The rough endoplasmic reticulum is present in the basal area of ​​the cell, while the smooth endoplastatic reticulum is the most abundant organelle in Sartoli cells.

Microtubules help maintain the distribution of the endoplasmic reticulum, as well as keep the mitochondria aligned. Sartoli cells possess phagocytic activity, for which they possess numerous lysosomes and multivesicular bodies. The Golgi apparatus, for its part, is relatively small.

Features

Nursing cells

Sertoli cells have been described as stem cells or as nurse cells. One of the nursing activities they carry out is linked to the transport of iron, micronutrients and other substances to the developing germ cell by means of proteins such as transferrin and ceruloplasmin.

In addition to providing iron required for germ cell development, Sertoli cells also remove and recycle potentially toxic iron from residual bodies. Some authors call this last function as recycling and waste material management.

Secretary

The secretory function of Sertoli cells is represented by hormones that can have autocrine, paracrine, and even endocrine activity. Paracrine functions include, for example, the signaling of germ cells to be targeted by follicle-stimulating hormones and tetosterone.

Additionally, after reaching puberty, Sertoli cells can regulate follicle-stimulating hormone production through the secretion of inhibin and activin, which act together.

It also produces various growth factors with paracrine activity, such as insulin-like growth factor 1 (IGF1), fibroblast growth factor (FGF), as well as transforming alpha (TGFA), which regulate the transformation of peritubular cells into Leydig cells, in addition to regulating their functioning.

Other hormones secreted by Sertoli cells that act during sex cell production include androgen binding protein (ABP), estradiol, and glial cell derived neutrophic factor (GDNF).

Immunoregulatory

Sertoli cells provide the testes with a unique immunoregulatory status, which has been demonstrated by transplanting testicular tissue into other different tissues, managing to survive for long periods of time.

This is because, otherwise, the meiotic condition of sex cells could cause them to be recognized by antibodies as exogenous and potentially pathogenic factors and consequently activate defense mechanisms for their destruction.

Among the molecules produced and secreted by Sertoli cells with immunoregulatory activity are, for example, the FAS / FAS Ligand system, protease inhibitor 9, CD40, CD59 or TGF-beta.

Physical protection

In addition to the immunoregulatory activity of the Sertoli cells, which protect the germ cells, the occluding junctions between them create a barrier that physically isolates the compartments where lymphocyte spermatogenesis takes place.

This barrier forms during puberty, when sperm production begins, and a break in it can trigger an immune response and cause male infertility.

This barrier acts dynamically allowing the migration of spermatocytes from the basal to the adluminal area of ​​the spermatic tube, but preventing, as already mentioned, the passage of lymphocytes.

Diseases

There are some diseases related to Sertoli cells, among which the following can be mentioned:

- Sertoli cell tumor

This type of tumor is rare, representing less than 1% of testicular tumors. It can present in three histological varieties:

Classic

Although on a few occasions (10-20%) it can become malignant, in cases in which it can metastasize to lymph nodes, bones and lung, survival rates are low.

This type of tumor does not present a hereditary component and is not related to any syndrome. The average age at which it manifests is 45 years.

Large cell calcifying

It is much more aggressive than the classic tumor and, unlike this one, it can be associated with inheritance or various syndromes, such as Peutz-Jeghers, Bourneville and also Carney complex.

The evil can appear early (17 years) or late (40 years), in both cases being a different behavior on their part. In the first case, it can present multifocality, bilaterality, as well as hormonal activity, while in the second case it does not. On the other hand, its aggressiveness is greater in cases of late onset.

Sclerosing

It is the least aggressive of the three varieties and to date no case of malignant behavior has been described. The mean age of onset is 35 years and, as in the case of late calcifying cell tumor, it does not present multifocality, bilaterality, or hormonal activity.

- Sertoli syndrome

Also known as germinal aplasia, it is a syndrome characterized by infertility caused by non-obstructive azoospermia (absence of germ cells). The causes of the syndrome are varied and among them are genetic disorders, mainly Klinefelter syndrome.

Other causes that have been associated with this syndrome include a history of cryptorchidism and / or varicocele. However, a high percentage of cases are of unknown origin.

- Sertoli-Leydig cell tumor

Also known as arrenoblastoma, it is a type of sex cord tumor that can lead to ovarian or testicular cancer. Its greatest occurrence occurs in young adults. It is generally benign and slow to develop.

Micrograph of a Leydig cell tumor of the testis. Taken and edited from: Nephron.

References

1. L. Johnson, DL Thompson Jr. & DD Varner (2008). Role of Sertoli cell number and function on regulation of spermatogenesis. Animal Reproduction Science.
2. K. Stouffs, A. Gheldof, H. Tournaye, D. Vandermaelen, M. Bonduelle, W. Lissens & S. Seneca (2016). Sertoli Cell-Only Syndrome: Behind the Genetic Scenes. BioMed Research International.
3. Sertoli cell. On Wikipedia. Recovered from en.wikipedia.org.
4. L. Etxegarai, L. Andrés, C. Ereño, FJ Bilbao, JI López (2005). Sclerosing Sertoli cell tumor. Spanish Journal of Pathology.
5. DW Fawcett (1975). Ultrastructure and function of the Sertoli cell. In: DW Hamilton & RO Greep (Eds.). Handbook of Physiology, vol. V. American Physiological Society.
6. LR França, RA Hess, JM Dufour, MC Hofmann & MD Griswold (2016). The Sertoli cell: one hundred fifty years of beauty and plasticity. Andrology.