Temsirolimus and antimüllerian hormone protect fertility and the ovarian reserve against chemotherapy-induced damage in a murine model

In: Fertility and Sterility · 2025 · vol. 125(1) , pp. 137–147 · doi:10.1016/j.fertnstert.2025.07.030 · PMID:40712967 · W4412701698
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Temsirolimus and anti-Müllerian hormone were found to protect fertility and the ovarian reserve from chemotherapy-induced damage in a murine model.

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The paper evaluated whether temsirolimus, anti-Müllerian hormone (AMH), or their combination can protect ovarian reserve and fertility outcomes after chemotherapy in a mouse model, using reproductive endpoints and ovarian assessments of follicle/ovarian status. The main finding was that treated animals showed preservation of fertility capacity and markers of ovarian reserve compared with chemotherapy-exposed controls. The study’s limitations include that results are based on an animal model with preclinical endpoints, which may not directly translate to humans. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

ObjectiveTo investigate the effects of temsirolimus (Tem) and recombinant antimüllerian hormone (AMH) on fertility and the ovarian reserve when associated with chemotherapy.DesignThirty-seven female mice were assigned to one of three treatment groups: control group; chemotherapy group; and gonadoprotection group. Five weeks after treatment, the mice underwent ovarian stimulation and were mated with males to evaluate residual fertility. Two days after mating, the animals were euthanized for embryo collection, and the ovaries were retrieved to assess the ovarian reserve and follicle damage.SubjectsThirty-seven Naval Medical Research Institute mice.ExposureThe control group (n = 10) was given a 100-μL injection of phosphate-buffered saline. The chemotherapy group (n = 13) received a single 100-μL injection of chemotherapy (120-mg/kg cyclophosphamide and 12-mg/kg busulfan). The gonadoprotection group (n = 14) was administered five injections of 5-mg/kg Tem over 1 week prior to chemotherapy, followed by a chemotherapy injection and then five injections of 5-μg recombinant AMH over the next 24 hours.Main outcome measuresEmbryo count, follicle count and morphology, and immunostaining for apoptosis (cleaved caspase-3), follicle activation (phospho-Akt), and proliferation (Ki67).ResultsThe control group showed the highest mean number of retrieved embryos (41.40 ± 14.74), closely followed by the gonadoprotection group (36.27 ± 17.22), whereas the chemotherapy group exhibited a significant reduction (20.63 ± 12.12) compared to both groups. Regarding the ovarian reserve, the control group showed the highest total follicle count (897.4 ± 392.8), with no difference compared to the gonadoprotection group (714.4 ± 283.9); however, there was a significant decline in the chemotherapy group (320.7 ± 145.5) compared with those in both groups. In terms of follicle apoptosis and activation, no significant difference was observed between groups. Follicle proliferation rates were significantly higher in the chemotherapy group (59.38% ± 14.67%) than in the control group (20.72% ± 10.52%); but gonadoprotective treatment did curtail follicle proliferation (42.23% ± 18.37%) compared with the chemotherapy group.ConclusionOur findings suggest that Tem and AMH show promise as gonadoprotective agents, potentially protecting the ovarian reserve against chemotherapy and thereby preserving fertility. This could offer patients who cannot benefit from currently available techniques brand new fertility preservation options.
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Temsirolimus and anti-Müllerian hormone protect fertility and the ovarian reserve against chemotherapy-induced damage in a murine model (2026) Fertility and Sterility — Vol. 125, n° 1, p. 137-147 (2025) (2026) Fertility and Sterility — Vol. 125, n° 1, p. 137-147 (2025) Open Access - Adobe PDF - 21.35 MB - Authors - Author Houeis, Lara UCLouvain - Author van der plancke, Graziella UCLouvain - Author Cacciottola, Luciana UCLouvain - Author Goudmaeker, Apolline UCLouvain - Author Kluyskens, Candice UCLouvain - Author Zipponi, Margherita UCLouvain - Author Dehoux, Jean-Paul UCLouvain - Author Donnez, Jacques UCLouvain - Author - et. al. - Affiliations - APA - Chicago - FWB Houeis, L., van der plancke, G., Cacciottola, L., Goudmaeker, A., Kluyskens, C., Zipponi, M., Dehoux, J.-P., Donnez, J., Dolmans, M.-M., & et al. (2026). Temsirolimus and anti-Müllerian hormone protect fertility and the ovarian reserve against chemotherapy-induced damage in a murine model. Fertility and Sterility, 125(1), 137-147. https://doi.org/10.1016/j.fertnstert.2025.07.030 (Original work published 2025)

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