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. 2025 Sep;32(9):2985-2996.
doi: 10.1007/s43032-025-01942-3. Epub 2025 Aug 14.

Investigation of the Efficacy of Umbilical Cord Mesenchymal Stem Cell and Melatonin Treatment in Premature Ovarian Failure Model

Aytaj Jafarzade  1   2 , Elvan Anadol  3 , Muzaffer Çaydere  4 , Durmuş Burgucu  5 , Canan Yılmaz  6 , Semih Ergişi  7 , Tamer Mungan  8
Affiliations

Investigation of the Efficacy of Umbilical Cord Mesenchymal Stem Cell and Melatonin Treatment in Premature Ovarian Failure Model

Aytaj Jafarzade et al. Reprod Sci. 2025 Sep.

Abstract

Premature Ovarian Insufficiency (POI) may develop in young female patients due to chemotherapy treatments, which causes infertility. In addition to stem cell treatment, which is an effective method for POI in recent years, melatonin, which has high antioxidant properties, is also known to be effective. This study aimed to investigate the efficacy of melatonin, human umbilical cord-derived mesenchymal stem cell (hucMSC), and melatonin + human umbilical cord-derived mesenchymal stem cell (hucMSC) treatments on POI in cyclophosphamide-induced POI models in rats. Sixty female animals were included in the experiment and randomly divided into the control, cyclophosphamide, cyclophosphamide + melatonin, cyclophosphamide + hucMSC, and cyclophosphamide + hucMSC + melatonin groups. Except for the control group, the POI model was created by administering intraperitoneal cyclophosphamide to other groups. Afterward, half of the animals were euthanized to investigate the effectiveness of the treatment, and AMH, E2, FSH, LH values in the blood of the euthanized animals were investigated by ELISA method. Follicle count was conducted in ovarian tissues, and the rate of apoptosis was determined by caspase-3 immunostaining. Fertility test was conducted on the group without euthanasia, and the number of baby rats was compared. Post-treatment E2 and AMH values were at the highest level in the cyclophosphamide + hucMSC + melatonin group. FSH value was at the lowest level in the cyclophosphamide + hucMSC + melatonin group. No significant difference was found between the groups in terms of LH value. Recovery was achieved with treatment in all follicle development stages. Particularly, the number of secondary and Graff follicles was statistically significantly higher in the cyclophosphamide + hucMSC + melatonin group. In caspase-3 immunostaining, the highest level of apoptosis was observed in the cyclophosphamide group, while the highest level of recovery was seen in the cyclophosphamide + hucMSC + melatonin group. As a result of fertility, the highest number of babies was observed in the cyclophosphamide + hucMSC + melatonin group following POI treatment. This study revealed that the success rate of POI treatment increases not only with stem cell treatment but also with combined treatment. If stem cell treatments are combined with melatonin with strong antioxidant properties, not as mono-therapy, for the purpose of infertility treatment, the effectiveness of the treatment increases.

Keywords: HucMSC; Melatonin; Premature ovarian insufficiency.

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Conflict of interest statement

Declarations: All authors have approved the manuscript submission, and the manuscript has not been published. It is not being considered for publication elsewhere, in whole or in part, in any language. Attestation Statement: Animal experiment study. Compliance with Ethical Standards: Written approval from the Gazi University Ethics Committee, number E-66332047–604.01.02–714506, was obtained for the study. Conflict of Interest: There is no conflict of interest between the authors. All authors read and approved the final version of the manuscript.

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