Cytotoxic effects of lead on the endocrine and exocrine sexual function of pubescent male and female rats. Demonstration of apoptotic activity

This study deals with the impact of chronic exposure to lead on male and female fertility in rats. Male and female rats (3 months old) were fed on commercial tablets (SICO, Sfax). For drinking, some rats were given distilled water (T = controls), the other ones were given distilled water enriched with lead acetate, either 3 (P1 group) or 6 mg ml-1 (P2 group), for 15, 30, 45, 60 or 90 days. In male rats, absolute and relative weights of testis, epididymis, prostate and seminal vesicles were found to significantly decrease at day 15 in the P2 group and at day 45 in the P1 group. However, at day 60, these absolute and relative weights returned to control values. Lead-induced pathological changes in spermatogenesis were observed at day 15 by histological study: arrest of cell germ maturation, changes in the Sertoli cells, and presence of apoptotic cells revealed by borated toluidine blue in the testis. Presence of lead deposits was observed after histochemical staining using sodium rhodizonate. Serum testosterone level was found to be lowered at day 15 in both (P1) and (P2) groups, to display a peak at day 60, then to return to controls values, in spite of the continuation of the treatment. In female rats, absolute and relative weights of ovary and uterus were found unchanged. The vaginal smears practiced in females revealed the oestrus phase in all groups. Exposed females were mated with control males, and fecundity was assessed 15 days later by counting the number of pregnancies and the number of concepti per pregnancy. Fertility was found to be reduced in females of P1 and P2 groups as compared to control females (T group). Lead level in blood was found to be poorly correlated with the level of poisoning, whereas lead accumulation in tail was found to be dose-dependent. Therefore, lead accumulation in tail appears as a more reliable biomarker of exposure to lead. In summary, our study shows that chronic exposure to lead causes a double sexual disorder in rats: first, disorder deals with the hormonal function, which is affected at the early stages of poisoning, but is rapidly corrected; second, disorder deals with the genital tract, affecting the testis and the ovary, resulting in a reduced fertility in both P1 and P2 females, in spite of the presence of a normal oestrus. The cytotoxic effect of lead in males seems to be related to an apoptotic process.