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 divide...

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Main Authors: Enes Karaman, Adem Yavuz, Erol Karakas, Esra Balcioglu, Busra Karaca, Hande Nur Doganay, Koray Gorkem Sacinti, Orhan Yildiz
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/4/345
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author Enes Karaman
Adem Yavuz
Erol Karakas
Esra Balcioglu
Busra Karaca
Hande Nur Doganay
Koray Gorkem Sacinti
Orhan Yildiz
author_facet Enes Karaman
Adem Yavuz
Erol Karakas
Esra Balcioglu
Busra Karaca
Hande Nur Doganay
Koray Gorkem Sacinti
Orhan Yildiz
author_sort Enes Karaman
collection DOAJ
description <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.
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spelling doaj-art-be73c0b385f147b8a9f089ba54512c4e2025-08-20T02:18:15ZengMDPI AGVaccines2076-393X2025-03-0113434510.3390/vaccines13040345Impact of mRNA and Inactivated COVID-19 Vaccines on Ovarian ReserveEnes Karaman0Adem Yavuz1Erol Karakas2Esra Balcioglu3Busra Karaca4Hande Nur Doganay5Koray Gorkem Sacinti6Orhan Yildiz7Department of Obstetrics and Gynecology, Faculty of Medicine, Nigde Omer Halisdemir University, 51240 Nigde, TurkeySchool of Health Sciences, Cappadocia University, 50400 Nevsehir, TurkeyOp. Dr. Erol Karakas Gynecology-Obstetrics-Genital Aesthetics and Sexual Health Clinic, 38140 Kayseri, TurkeyDepartment of Histology and Embryology, Faculty of Medicine, Erciyes University, 38030 Kayseri, TurkeyHakan Cetinsaya Good Clinical Practice and Research Center, 38030 Kayseri, TurkeyObsterics annd Gynecology Clinic, Nigde Omer Halisdemir University Training and Research Hospital, 51100 Nigde, TurkeyObstetrics and Gynecology Clinic, Aksaray Training and Research Hospital, 68200 Aksaray, TurkeyDeparment of Clinical Microbiology and Infectious Disease, Faculty of Medicine, Erciyes University, 38030 Kayseri, Turkey<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.https://www.mdpi.com/2076-393X/13/4/345ratmRNA vaccineinactivated COVID-19 vaccinesovarian reservefollicular atresia
spellingShingle Enes Karaman
Adem Yavuz
Erol Karakas
Esra Balcioglu
Busra Karaca
Hande Nur Doganay
Koray Gorkem Sacinti
Orhan Yildiz
Impact of mRNA and Inactivated COVID-19 Vaccines on Ovarian Reserve
Vaccines
rat
mRNA vaccine
inactivated COVID-19 vaccines
ovarian reserve
follicular atresia
title Impact of mRNA and Inactivated COVID-19 Vaccines on Ovarian Reserve
title_full Impact of mRNA and Inactivated COVID-19 Vaccines on Ovarian Reserve
title_fullStr Impact of mRNA and Inactivated COVID-19 Vaccines on Ovarian Reserve
title_full_unstemmed Impact of mRNA and Inactivated COVID-19 Vaccines on Ovarian Reserve
title_short Impact of mRNA and Inactivated COVID-19 Vaccines on Ovarian Reserve
title_sort impact of mrna and inactivated covid 19 vaccines on ovarian reserve
topic rat
mRNA vaccine
inactivated COVID-19 vaccines
ovarian reserve
follicular atresia
url https://www.mdpi.com/2076-393X/13/4/345
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