FGF21 negatively affects long-term female fertility in mice

Article Article scientifique Article FGF21 negatively affects long-term female fertility in mice eng 2022-11-11 2022-11 author Moeckli Beat 0000-0002-9020-8416 848954 author Pham Thuy Vy 0000-0003-0601-3120 754110 author Slits Florence 782467 author Latrille Samuel 0000-0001-7361-5514 989755 author Peloso Andréa 0000-0002-3089-0230 878393 author Delaune Vaihere 0000-0001-8931-0977 839496 author Oldani Graziano 776352 author Lacotte Stéphanie 0000-0002-5921-6389 714209 author Toso Christian 0000-0003-1652-4522 92271 e11490 10.1016/j.heliyon.2022.e11490 36406708 2405-8440 PMC9667250 https://linkinghub.elsevier.com/retrieve/pii/S2405844022027785 Objective: Obesity and associated liver disease are a growing public health concern. Pharmacological agents to treat non-alcoholic fatty liver disease are limited. FGF21, a hormone secreted by the liver and potent metabolic modulator, is a promising therapeutic target for this indication with several analogs currently in clinical development. However, concerns about a negative effect of FGF21 on female fertility have not been fully addressed. Methods: After induction of obesity, female C57BL/6N mice received a 7-day course of subcutaneously administered FGF21. Control groups received either high-fat diet (HFD) or a normal diet (ND). The mothers were then mated with lean males for 12 weeks. The estrous cycle was recorded for two weeks after breeding. The metabolic phenotype, liver steatosis and reproductive organs were assessed at sacrifice 14 weeks after treatment. Results: A short-course treatment of FGF21 leads to weight reduction during treatment but has no long-term impact on liver steatosis. A treatment with FGF21 leads to a reduction in the number of pregnancies (0 vs 1, p = 0.019) and no viable pup was born to a mother previously treated with FGF21. The FGF21 treatment affected the number of cycles (1 vs 3, p = 0.048) and amount in diestrus (54 vs 75%, p = 0.008) 12 weeks after the treatment. Additionally, the number of corpora lutea (0.8 vs 3.0, p = 0.016), and mature follicles (0 vs 1, p = 0.037) was reduced compared to the ND group while uterine histology remained unaffected. Conclusion: A short-term treatment with FGF21 has a long-term effect on female fertility in mice. This represents a potential safety concern for FGF21 analogs currently in clinical development. Reproductive health outcomes should be included in upcoming clinical trials. FGF21 Fertility High-fat diet Non-alcoholic fatty liver disease Dewey 617 Swiss National Science Foundation Impact of the gut-liver axis on de novo and recurrent hepatocellular carcinoma in the presence non-alcoholic fatty liver disease 182471 CH Projects Fondation Leenaards 5489 57 Département de chirurgie 222 false 562 Transplantation et hépatologie 905 1329 Chirurgie viscérale (HUG) https://doi.org/10.26037/yareta:5rk3keet5rdi5c6gx3xznaanry https://github.com/moecklib Heliyon 8 11 86f1208a-8fbd-40e3-b3d0-5dfb8c964635 Article (Published version) Public Article-scientifique-from-unpaywall.pdf 2539624 application/pdf CC BY-4.0 openAccess Faculté de médecine / Section de médecine clinique / Département de chirurgie

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FGF21 negatively affects long-term female fertility in mice	Heliyon			2022	210	259

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Latrille, Samuel