Testis, fetal

Figure 1 The major hormones involved in growth and funetion of the fetal/neonatal testis illustrating how exogenous, environmental oestrogens eould disrupt the normal balanee of these meehanisms.

Table 1 Sites of androgen and oestrogen reeeptors and aromatase aetivity in the testis and assoeiated duets during fetal/perinatal life in the rat ...

Testosterone, the principal male sex steroid hormone, is synthesized in five steps from cholesterol, as shown below. In the last step, five isozymes catalyze the 17/3-hydroxysteroid dehydrogenase reactions that interconvert 4-androstenedione and testosterone. Defects in the synthesis or action of testosterone can impair the development of the male phenotype during embryogenesis and cause the disorders of human sexuality termed male pseudohermaphroditism. Specifically, mutations in isozyme 3 of the 17/3-hydroxysteroid dehydrogenase in the fetal testis impair the for-... 

Majdic, G., Sharpe, R.M., and Oshaughnessy, PJ. et al. (1996). Expression of cytochrome P450 17 alpha-hydroxylase/C 17-20 lyase in the fetal rat testis is reduced by maternal exposure to exogenous estrogens. Endocrinology 137, 1063-1070. 

Borch J, Axelstad M, Vinggaard AM, Dalgaard M (2006) Diisobutyl phthalate has comparable antiandrogenic effects to di-n-butyl phthalate in fetal rat testis. Toxicol Lett 163 183-190... 

Paul C., S.M. Rhind, C.E. Kyle, H. Scott, C. McKinell, and R.M. Sharpe (2005). Cellular and hormonal dismption of fetal testis development in sheep reared on pasture treated with sewage sludge. Environmental Health Perspectives 113 1580-1587. 

Autosomal recessive mutations in the 17/3-hydroxysteroid dehydrogenase (17/3HSD) 3 gene impair the formation of testosterone in the fetal testis and give rise to genetic males with female external genitalia. Such individuals are usually raised as females, but virilize at the time of expected puberty as the result of increases in serum testosterone. More than 14 mutations have now been identified [20]. 

As many malignant tumors resemble fetal tissue in their biochemical composition, this result is consistent with the observed absence of SGG from immature human testis (15,26). Another tentative interpretation of this finding is that seminoma cells derive from a cell stage prior to that of the primary spermatocyte, thus accounting for their inability to synthesize SGG. 

Less is known of the risks faced by males exposed to DES during fetal development. Animal studies have revealed that male rodents exposed to DES have increased incidence of prostatic metaplasia. Epidemiological studies of DES sons have suggested increased risk of various testicular abnormalities including epididymal cysts, testicular varicoceles, and undescended testis. Hyperplasia and metaplasia of the prostatic ducts in DES sons also have been reported. 

Cimetidine (for treatment of peptic ulcers) competes with dihydrotestosterone for receptors in the testis and accessory sex glands. The more common sequelae are low sperm count and gynacomastia. Epidemiological evidence has shown that occupation exposure to oral contraceptives can induce gynacomastia in exposed males. Diethylstilbestrol (DES) antagonizes the activity of fetal testosterone. In the male offspring, testicular hypoplasia, abnormal semen parameters, and infertility result. Ketoconazole has be shown to be transported to the seminal fluid and to immobilize the sperm. 

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