Karaman Enes, Yavuz Adem, Karakas Erol, Balcioglu Esra, Karaca Busra, Doganay Hande Nur, Sacinti Koray Gorkem, Yildiz Orhan
Department of Obstetrics and Gynecology, Faculty of Medicine, Nigde Omer Halisdemir University, 51240 Nigde, Turkey.
School of Health Sciences, Cappadocia University, 50400 Nevsehir, Turkey.
Vaccines (Basel). 2025 Mar 24;13(4):345. doi: 10.3390/vaccines13040345.
: 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. : Thirty female Wistar albino rats, aged 16-24 weeks, were randomly divided into three groups ( = 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. 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 ( < 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 ( < 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 ( < 0.05). The serum AMH level was diminished with the mRNA vaccination in comparison with the control and inactivated groups. : 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.
本研究旨在阐明信使核糖核酸（mRNA）疫苗和新型冠状病毒肺炎（COVID-19）灭活疫苗对大鼠卵巢组织学及储备功能的影响。30只16 - 24周龄的雌性Wistar白化大鼠被随机分为三组（每组n = 10）：对照组、mRNA疫苗组和灭活疫苗组。每个疫苗组按人用等效剂量接种两剂（分别在第0天和第28天）。第二次接种后四周，采集卵巢组织进行分析。采用免疫组织化学分析评估卵巢卵泡中转化生长因子β1（TGF-β1）、血管内皮生长因子（VEGF）、半胱天冬酶-3（caspase-3）和抗苗勒管激素（AMH）的表达。两种疫苗均显著增加了TGF-β1、VEGF和caspase-3的表达，mRNA疫苗组的影响更为明显。相反，初级卵泡、次级卵泡和窦状卵泡颗粒细胞中的AMH表达显著降低（P < 0.001）。相对于对照组，灭活疫苗组的原始卵泡、初级卵泡和次级卵泡数量显著减少，与灭活疫苗组相比，mRNA疫苗组的上述卵泡数量进一步减少（P < 0.001）。此外，与其他组相比，mRNA疫苗组的窦状卵泡和排卵前卵泡数量减少，闭锁卵泡数量增加（P < 0.05）。与对照组和灭活疫苗组相比，mRNA疫苗接种后血清AMH水平降低。我们的研究结果表明，mRNA疫苗和COVID-19灭活疫苗可能对大鼠的卵巢储备功能产生不利影响，主要是通过加速卵泡丢失以及在卵泡发生过程中改变凋亡途径。鉴于在大鼠模型中的这些观察结果，需要进一步研究这些疫苗对人类卵巢储备功能的影响。
