Gonadal sex steroid hormone secretion after exposure of male rats to estrogenic chemicals and their combinations

Environmental chemicals can interfere with the endocrine axis hence they are classified as endocrine disrupting chemicals (EDCs). Bisphenol S (BPS) is used in the manufacture of consumer products because of its superior thermal stability and is thought to be a safe replacement chemical for its analog bisphenol A (BPA). However, the safety profile of these compounds alone or in the presence of other EDCs is yet to be fully investigated. Also, the estrogenic chemical 17 alpha-ethinyl estradiol (EE2) and a constituent of female oral contraceptives for women, is present in water supplies. To simulate concurrent exposure of the population to chemical mixtures, we investigated the effects of BPA, BPS, EE2, and their combinations on sex steroid secretion in the growing male rat gonad. Prepubertal and pubertal male rats at 21 and 35 days of age were provided test chemicals in drinking water (parts per billion) for 14 days. At termination of exposure, some individual chemical effects were modified by exposure to chemical combinations. Single chemical exposures markedly decreased androgen secretion but their combination (e.g., BPA + BPS + EE2) caused the opposite effect, i.e., increased Leydig cell T secretion. Also, the test chemicals acting alone or in combination increased testicular and Leydig cell 17 beta-estradiol (E2) secretion. Chemical-induced changes in T and E2 secretion were associated with altered testicular expression of the cholesterol side-chain cleavage (Cyp11a1) and 17 beta-hydroxysteroid dehydrogenase (Hsd17 beta) enzyme protein. Additional studies are warranted to understand the mechanisms by which single and chemical combinations impact function of testicular cells and disrupt their paracrine regulation.

Automated summary

Environmental chemicals can disrupt the endocrine axis and are classified as endocrine disrupting chemicals. Some commonly used consumer product chemicals (such as Bisphenol S and 17 alpha-ethinyl estradiol) may have adverse effects on the population. In animal models, exposure to individual chemicals or combinations of multiple chemicals can lead to disturbances in sex steroid secretion.