Prenatal cadmium exposure has intergenerational adverse effects on the Sertoli cells through FSHR pathway.

Abstract

Exposure to cadmium (Cd) during pregnancy can potentially harm the reproductive system of male offspring, although the full extent of its heritable effects remains partially unresolved. In this study, we examined the intergenerational impacts of Cd using a distinct male-lineage transmission model. Pregnant Sprague-Dawley (SD) female rats (F0) were administered control or cadmium chloride (0.5, 1, 2 mgp/day) via intragastric administration from gestation day 1 to 20. Subsequently, the first filial generation (F1) male rats were mated with untreated females (not exposed to Cd) to produce the second filial generation (F2). Histopathological analysis of the F1 and F2 generations revealed abnormal testicular development, while ultrastructural examination indicated damage to Sertoli cells. Cd exposure also led to alterations in serum hormone levels (GnRH, FSH) and reduced FSHR protein expression in Sertoli cells in the F1 generation. Furthermore, Cd affected the mRNA and protein expression of FSHR pathway factors and DNA methyltransferase, albeit with distinct patterns and inconsistencies observed between the F1 and F2 generations. Overall, our findings indicate that prenatal Cd exposure, using a male-lineage transmission model, can induce inter-generational effects on male reproduction, particularly by causing toxicity in Sertoli cells. This effect appears to be primarily mediated through disruptions in the FSHR pathway and changes in DNA methyltransferase activity in the male testes.