Damage response and postnatal compensatory repair in the male offspring mouse reproductive system following gestational cadmium exposure.

Cadmium (Cd), an environmental toxicant, is known to cause significant damage to reproductive systems in human and animals. However, the detrimental effects of maternal Cd exposure during gestation on male offspring and the underlying mechanisms remain unknown. In this study, pregnant mice were exposed to Cd (32 mg/l) in drinking water throughout gestation to investigate the mechanisms underlying testicular and sperm injury and repair in male offspring. Results showed that maternal Cd exposure caused growth inhibition in male offspring at birth, accompanied by testicular DNA damage and upregulation of Rad51, a key protein involved in homologous recombination repair. After delivery, when Cd was removed, the male offspring exhibited compensatory growth and development. At 7 weeks of age, despite abnormally enlarged seminiferous tubules, spermatogonial stem cell meiosis arrest, and reduced total sperm motility, DNA damage levels, DNA repair capacity, and the motility function of surviving sperm were all at normal levels. Compared with controls, the offspring at 7 weeks of age showed no alterations in global 5-methylcytosine (5-mC) of sperm, whereas DNA methylation of Line1 were decreased. Meanwhile, DNA methylation of imprinted genes H19 and Peg3, which regulate sperm quality and post-fertilization embryonic development, remained normal. Cd exposure during gestation led to transcriptomic abnormalities in the testes of newborn male offspring, but these abnormalities were gradually repaired during postnatal growth and development. These findings indicate that although gestational Cd exposure impairs reproductive function of male offspring, postnatal growth and development, coupled with DNA repair mechanisms, can partially restore their reproductive potential.