Sertoli cells as a target for reproductive hazards

Abstract

Male fertility can be impaired by various toxicants. Some of them are known to target mainly Sertoli cells, which play an essential role in spermatogenesis. In this study, the in vitro response of immature rat Sertoli cells to various environmental pollutants, including pesticides, oestrogenic compounds and heavy metals, has been investigated. Mitochondrial dehydrogenase activity has been used to measure Sertoli cell viability, while production of lactate and secretion of inhibin B have been used as general and specific cell markers. Sertoli cell viability was not affected after 24-h exposure to lindane, DDT, ethinyloestradiol or bisphenol A in the concentration range analysed (up to 100, 25 or 50 microM, respectively). In contrast, mercury(II) (EC50 = 31 microM) and cisplatin (15% decrease in viability at 100 microM) induced some cytotoxic effect. With the exception of the pesticide DDT, all chemicals investigated induced a significant dose-dependent increase in lactate production after 24-h exposure to Sertoli cells. Owing to the cytotoxic effect of mercury(II), lactate levels dropped again at concentrations above 20 microM. The pesticide lindane (but not DDT) and both oestrogens significantly increased the production of the Sertoli cell specific hormone inhibin B without affecting cell viability. In contrast, the heavy metals mercury(II) and platinum(II) markedly decreased inhibin B levels. This sharp decrease was already significant at metal concentrations that reduced Sertoli cell viability only moderately (10-15%). In conclusion, the secretion of lactate and inhibin B by immature rat Sertoli cells seems to be a useful and sensitive marker with which to explore potential Sertoli cell toxicants.

Analysis of Differentially Regulated Proteins in TM4 Cells Treated with Bisphenol A

“…The results of this study showed that BPA strongly affected TM4 cell viability and morphology at concentrations of BPA over 150 M. This anomalous situation has also been discussed in previous reports. 10,20) Especially, the viability of TM4 cells decreased to about 60% of that of untreated cells after exposure to over 300 M of BPA for 16 h.…”

Modifications in Rat Testicular Morphology and Increases in IFN-γ Serum Levels by the Oral Administration of Subtoxic Doses of Mercuric Chloride

“…Decreased cell viability parallels a reduction in luteinizing hormone-stimulated testosterone production by Leydig cells [Ng and Liu 1990]. Sertoli cells which play an essential role in spermatogenesis, are known to be the target of various toxicants [Monsees et al 2000]. Moreover, the toxicity of mercury on isolated Sertoli cells grown in culture is higher than that of cadmium or arsenic [Espevik et al 1982].…”

Adverse Effects of Low Level Heavy Metal Exposure on Male Reproductive Function

“…Treatment of rats with inorganic (50 or 100 mg/kg) or organic (5 or 10 mg/g) mercury for 90 days induced Leydig cell disintegration, inhibited the activity of 3b-hydroxysteroid dehydrogenase (3-b-HSD), an enzyme critical for TE production, and decreased TE levels [Chowdhury et al 1985;Vachhrajani and Chowdhury 1990]. Rat Sertoli cells incubated in vitro with 31 mM (6.22 mg/L) of inorganic mercury produced lower levels of inhibin b [Monsees et al 2000]. The number of rat epididymal sperm declined after incubation with inorganic mercury and a dose-dependent decrease in motility was also noted [Rao and Gangadharan 2008].…”