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FGF21 negatively affects long-term female fertility in mice

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 severa...

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Autores principales: Moeckli, Beat, Pham, Thuy-Vy, Slits, Florence, Latrille, Samuel, Peloso, Andrea, Delaune, Vaihere, Oldani, Graziano, Lacotte, Stéphanie, Toso, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9667250/
https://www.ncbi.nlm.nih.gov/pubmed/36406708
http://dx.doi.org/10.1016/j.heliyon.2022.e11490
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author Moeckli, Beat
Pham, Thuy-Vy
Slits, Florence
Latrille, Samuel
Peloso, Andrea
Delaune, Vaihere
Oldani, Graziano
Lacotte, Stéphanie
Toso, Christian
author_facet Moeckli, Beat
Pham, Thuy-Vy
Slits, Florence
Latrille, Samuel
Peloso, Andrea
Delaune, Vaihere
Oldani, Graziano
Lacotte, Stéphanie
Toso, Christian
author_sort Moeckli, Beat
collection PubMed
description 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.
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spelling pubmed-96672502022-11-17 FGF21 negatively affects long-term female fertility in mice Moeckli, Beat Pham, Thuy-Vy Slits, Florence Latrille, Samuel Peloso, Andrea Delaune, Vaihere Oldani, Graziano Lacotte, Stéphanie Toso, Christian Heliyon Research Article 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. Elsevier 2022-11-11 /pmc/articles/PMC9667250/ /pubmed/36406708 http://dx.doi.org/10.1016/j.heliyon.2022.e11490 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Moeckli, Beat
Pham, Thuy-Vy
Slits, Florence
Latrille, Samuel
Peloso, Andrea
Delaune, Vaihere
Oldani, Graziano
Lacotte, Stéphanie
Toso, Christian
FGF21 negatively affects long-term female fertility in mice
title FGF21 negatively affects long-term female fertility in mice
title_full FGF21 negatively affects long-term female fertility in mice
title_fullStr FGF21 negatively affects long-term female fertility in mice
title_full_unstemmed FGF21 negatively affects long-term female fertility in mice
title_short FGF21 negatively affects long-term female fertility in mice
title_sort fgf21 negatively affects long-term female fertility in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9667250/
https://www.ncbi.nlm.nih.gov/pubmed/36406708
http://dx.doi.org/10.1016/j.heliyon.2022.e11490
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