Impact of mRNA and Inactivated COVID-19 Vaccines on Ovarian Reserve

<b>Objectives</b>: This study aimed to elucidate the effects of messenger RNA (mRNA) and inactivated coronavirus disease 2019 (COVID-19) vaccines on ovarian histology and reserve in rats. <b>Methods</b>: Thirty female Wistar albino rats, aged 16-24 weeks, were randomly divided into three groups (<i>n</i> = 10): control, mRNA vaccine, and inactivated vaccine groups. Each vaccine group received two doses (on day 0 and day 28) at human-equivalent doses. Four weeks post-second vaccination, ovarian tissues were harvested for analysis. <b>Results:</b> Immunohistochemical analysis was performed to evaluate the expression of transforming growth factor beta-1 (TGF-β1), vascular endothelial growth factor (VEGF), caspase-3, and anti-Müllerian hormone (AMH) in ovarian follicles. Both vaccines induced significant increases in TGF-β1, VEGF, and caspase-3 expression, with more pronounced effects in the mRNA vaccine group. Conversely, AMH expression in the granulosa cells of primary, secondary, and antral follicles showed marked reductions (<i>p</i> < 0.001). The counts of primordial, primary, and secondary follicles decreased significantly in the inactivated vaccine group relative to controls and further in the mRNA vaccine group compared to the inactivated group (<i>p</i> < 0.001). Additionally, the mRNA vaccine group exhibited a decrease in antral and preovulatory follicles and an increase in atretic follicles compared to the other groups (<i>p</i> < 0.05). The serum AMH level was diminished with the mRNA vaccination in comparison with the control and inactivated groups. <b>Conclusions</b>: Our findings suggest that both mRNA and inactivated COVID-19 vaccines may detrimentally impact ovarian reserve in rats, primarily through accelerated follicular loss and alterations in apoptotic pathways during folliculogenesis. Given these observations in a rat model, further investigations into the vaccines' effects on human ovarian reserve are needed.