Reproductive toxicants in the environment and their role in some human diseases (Сlinic)

In recent decades, there has been a fairly active debate on the role of genetic predisposition, average factors, adverse effects of reproductive toxins, infections, special behaviour that includes harmful habits for human diseases and not to implement their reproductive plans. Environmental disasters, the Covid-19 pandemic, the incorporation of the modern human and industrial waste, forest fires, excessive radiation following the national tragedy of Chernobyl has become global, not only the age of dependent diseases, but the disorders of the main functional systems of the female and male organism that result in reproductive function, reduce the quality of life and duration. Unfavourable medium effects, disturb the process of interacting with the genotype of the organism in shaping the phenotype. This information is needed by doctors to develop periconceptology, which is the task of this clinical lecture.

Metals and female reproductive toxicity

Research into occupational exposure of metals and consequences of reproductive systems has made imperative scientific offerings in the preceding few decades. Early research works focused on possible effects on the reproductive functions rather than the complete reproductive health of the woman. Later, it was realized that metals, as reproductive toxins, may also induce hormonal changes affecting other facets of reproductive health such as the menstrual cycle, ovulation, and fertility. Concern is now shifting from considerations for the pregnant woman to the entire spectrum of occupational health threats and thus reproductive health among women.

Inhibition of CYP450scc expression in dioxin-exposed rat Leydig cells

Polychlorinated dibenzo-p-dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have been recognized as highly potent developmental and reproductive toxins. We have previously demonstrated effects of TCDD in modulating the expression of rat Sertoli cell secretory products and markers for cell–cell interaction. In this study, we examined the direct biological effects of TCDD in rat Leydig cell primary cultures. Mature rat Leydig cells were purified by Percoll gradient centrifugation and the cell purity was determined by 3β-hydroxysteroid dehydrogenase (3β-HSD) staining and a testosterone induction assay. To examine TCDD-induced biological consequences, we measured the changes in the secretion of progesterone and testosterone, as well as transcript levels of some selected steroidogenic enzymes (i.e. StAR, P450scc, 3β-HSD and CYP17α), in TCDD/human chorionic gonadotropin (hCG) co-treated cells. Our results indicated that TCDD (0.2 or 2 ng/ml) treatment significantly suppressed hCG (5 or 10 ng/ml)-induced testosterone secretion. The suppressive effect aligned with a reduction of progesterone secretion (P<0.05), as well as a decrease of P450scc mRNA and protein expression (P<0.05). The mechanistic action of TCDD was found to be via the reduction of cellular cAMP levels in the hCG-treated cells. This observation was further confirmed, as the TCDD-mediated suppressive effect could be reversed by dibutyryl cAMP co-treatment. The data indicate that TCDD can modulate cAMP signaling in rat Leydig cells to affect the process of steroidogenesis.