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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844022027785 |
| _version_ | 1811321711531917312 |
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| author | Beat Moeckli Thuy-Vy Pham Florence Slits Samuel Latrille Andrea Peloso Vaihere Delaune Graziano Oldani Stéphanie Lacotte Christian Toso |
| author_facet | Beat Moeckli Thuy-Vy Pham Florence Slits Samuel Latrille Andrea Peloso Vaihere Delaune Graziano Oldani Stéphanie Lacotte Christian Toso |
| author_sort | Beat Moeckli |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T13:21:24Z |
| format | Article |
| id | doaj.art-2ad3d0355d874458b8da622a61c948d8 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-13T13:21:24Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-2ad3d0355d874458b8da622a61c948d82022-12-22T02:45:17ZengElsevierHeliyon2405-84402022-11-01811e11490FGF21 negatively affects long-term female fertility in miceBeat Moeckli0Thuy-Vy Pham1Florence Slits2Samuel Latrille3Andrea Peloso4Vaihere Delaune5Graziano Oldani6Stéphanie Lacotte7Christian Toso8Department of Visceral Surgery, Geneva University Hospital, Geneva, Switzerland; Laboratory of Transplantation and Hepatology, University of Geneva, Geneva, SwitzerlandDepartment of Visceral Surgery, Geneva University Hospital, Geneva, SwitzerlandLaboratory of Transplantation and Hepatology, University of Geneva, Geneva, SwitzerlandLaboratory of Transplantation and Hepatology, University of Geneva, Geneva, SwitzerlandDepartment of Visceral Surgery, Geneva University Hospital, Geneva, Switzerland; Laboratory of Transplantation and Hepatology, University of Geneva, Geneva, SwitzerlandDepartment of Visceral Surgery, Geneva University Hospital, Geneva, Switzerland; Laboratory of Transplantation and Hepatology, University of Geneva, Geneva, SwitzerlandDepartment of Visceral Surgery, Geneva University Hospital, Geneva, Switzerland; Laboratory of Transplantation and Hepatology, University of Geneva, Geneva, SwitzerlandLaboratory of Transplantation and Hepatology, University of Geneva, Geneva, Switzerland; Corresponding author.Department of Visceral Surgery, Geneva University Hospital, Geneva, Switzerland; Laboratory of Transplantation and Hepatology, University of Geneva, Geneva, SwitzerlandObjective: 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.http://www.sciencedirect.com/science/article/pii/S2405844022027785FGF21FertilityNon-alcoholic fatty liver diseaseHigh-fat diet |
| spellingShingle | Beat Moeckli Thuy-Vy Pham Florence Slits Samuel Latrille Andrea Peloso Vaihere Delaune Graziano Oldani Stéphanie Lacotte Christian Toso FGF21 negatively affects long-term female fertility in mice Heliyon FGF21 Fertility Non-alcoholic fatty liver disease High-fat diet |
| 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 | FGF21 Fertility Non-alcoholic fatty liver disease High-fat diet |
| url | http://www.sciencedirect.com/science/article/pii/S2405844022027785 |
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