Maternal genetic effect on apoptosis of ovarian granulosa cells induced by cadmium

To investigate the maternal genetic effects of cadmium (Cd) -induced apoptotic in ovarian granulosa cells (OGCs). Herein, pregnant Sprague-Dawley (SD) rats were treated with CdCl₂ from day 1 to day 20, F1 and F2 female rats were mated with untreated males to produce F2 and F3 generations. Under this model, significant apoptotic changes were observed in F1 OGCs induced by Cd (Liu et al., 2021). In this study, no apoptotic bodies were found in F2 while the mitochondrial membrane potential level decreased significantly but not in F3. Moreover, significant changes in bcl-xl and Cle-CASPASE-9/Pro-CASPASE-9 ratio were observed in F2 which disappears in F3. The DNA methylation sequencing and microRNAs (miRNAs) microarray reveals different gene methylation and miRNAs changes in F2 and F3. Notably, miR-132-3p, miR-199a-5p, and miR-1949 were upregulated in F1 while downregulated in F2 and F3 in which apoptosis gradually disappeared. Further, miRNA maturation-related genes and transcription factors have different expression patterns in F1-F3. These results indicate that maternal genetic intergenerational/transgenerational effect of Cd-induced OGCs apoptotic was significantly attenuated and disappeared, which was related to self-repair regulation of apoptosis-related genes. The changes in apoptosis-related miRNAs and DNA methylation may be important, and the role of transcription factors deserve attention.