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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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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. |
format | Online Article Text |
id | pubmed-9667250 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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