Sertoli cell-only syndrome (SCO) is also known as Del Castillo syndrome and germ cell aplasia. Sertoli cells are found in the convoluted seminiferous tubules and form part of the blood-testis barrier in males. They also play an important role in spermatogenesis which is sperm production. The cells respond to a hormone called follicle-stimulating hormone (FSH) that is released by the hypothalamus.[1] Patients with Sertoli cell-only syndrome are typically males between ages 20 to 40. In Sertoli cell-only syndrome, only Sertoli cells line the seminiferous tubules of the testis, and the patients have very low or absent spermatogenesis. These patients are typically normal on physical examination as this condition presents with infertility without sexual abnormality. Diagnosis is usually made based on testicular biopsy findings. Most cases are multifactorial and idiopathic. Patients can still reproduce with assisted reproductive technology.

Sertoli cells have multiple vital reproductive functions in males. They play an essential role in the proper growth and development of spermatogonia by secreting substances required for their growth and nourishment. Sertoli cells also secrete the anti-Mullerian hormone, AMH, that leads to the regression of Mullerian ducts in a male fetus. This hormone prevents the development of any internal female reproductive organs during the early stages of embryogenesis in a male fetus.

Sertoli cells also secrete inhibin-B which provides the down-regulatory effect of follicle-stimulating hormone secretion on the hypothalamus. Activin is another product secreted by Sertoli cells. It provides positive feedback on the hypothalamus for spermatogenesis and leads to a higher FSH level.

There are no exact figures for the prevalence of this condition, but it is estimated that less than 5% to 10% of infertile men may be having Sertoli cell-only syndrome. They present with only infertility. While there is no racial predilection, it is slightly more common in Caucasian males. The most commonly affected age group involves adults of 20 to 40 years old.

Sertoli cell-only syndrome most likely is a multifactorial and idiopathic condition. The diagnosis is often made when young male patients come for an evaluation for infertility. They present with reduced or absent spermatogenesis and usually have a normal physical examination.

Multiple possible pathways may be involved in the pathogenesis of this condition. Researchers hypothesize that congenital absence of germ cells can result from proper failure of migration of gonocytes. The Yq11 region is also known as the azoospermia factor region (AZF region). Microdeletions in the Yq11 region of the Y chromosome, especially in the AZFb/b+c region, have been found in some patients with SCO syndrome and is another possible cause of the disease. Deletions between palindromes P5 and P1 and between P4 and P1 have also been reported. Yang et al. also hypothesized that two deletions in the interval region between P4 and P3 might also be involved in the pathophysiology of the condition. Apoptotic elimination and altered maturation of germ cells through mutations of Fas, FasL, and active caspase-3 have also been reported recently in the literature.[2][3][4][5]

The patients present with normal levels of luteinizing hormone (LH) and testosterone. The low level of inhibin-B leads to a higher than normal level of follicle-stimulating hormone (FSH). A study conducted by Stouffs et al. showed that in Caucasian males with SCO syndrome, karyotype abnormalities, such as Klinefelter syndrome, were the most common abnormality seen.[6]

The pathophysiology of the disease can be summarized as follows:

• Mostly idiopathic
• Genetic as discussed above
• Toxin exposure leading to lower spermatogenesis
• Radiation exposure to the testicular region
• History of trauma leading to decreased sperm cell production
• Viral infection

According to Nistal et al., histology of biopsies can vary. They can appear as normal mature cells, while others might present as involuting, immature, or dysgenetic. The shapes of the cell and nucleus as well as changes in the cytoplasm are helpful for categorizing them.[7]