Dapagliflozin partially restores reproductive function in MC4R KO obese female mice

in Journal of Endocrinology
Authors:
Ling Cui School of Biomedical Science, University of Queensland, St Lucia, Brisbane, Queensland, Australia
Department of Reproduction and Infertility, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China

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Chunlu Tan School of Biomedical Science, University of Queensland, St Lucia, Brisbane, Queensland, Australia

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Lili Huang School of Biomedical Science, University of Queensland, St Lucia, Brisbane, Queensland, Australia

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Weihao Wang School of Biomedical Science, University of Queensland, St Lucia, Brisbane, Queensland, Australia

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Zhengxiang Huang School of Biomedical Science, University of Queensland, St Lucia, Brisbane, Queensland, Australia

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https://orcid.org/0000-0002-1194-2701
,
Fang Geng School of Biomedical Science, University of Queensland, St Lucia, Brisbane, Queensland, Australia

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Mengjun Wu Department of Reproduction and Infertility, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China

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Xiaolin Chen Endocrinology Department, Renmin Hospital of Wuhan University, Wuchang District, Wuhan, Hubei Province, China

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Michael Cowley Department of Physiology, Monash University, Clayton, Victoria, Australia

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Ferdinand Roelfsema Endocrinology and Metabolism, Leiden University, Leiden, Netherlands

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Chen Chen School of Biomedical Science, University of Queensland, St Lucia, Brisbane, Queensland, Australia

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https://orcid.org/0000-0003-2104-534X

Correspondence should be addressed to C Chen: chen.chen@uq.edu.au
DOI:
https://doi.org/10.1530/JOE-21-0449
Volume/Issue:
Volume 254: Issue 2
Article Type:
Research Article
Page Range:
65–76
Online Publication Date:
17 Jun 2022
Copyright:
© Society for Endocrinology 2022
Restricted access
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Obese women often have certain degree of reproductive dysfunction with infertility. Although the clinical impact of obesity on female infertility has been extensively studied, the effective and targeted treatment is still lacking. Melanocortin-4-receptor knock-out (MC4R KO) mouse is an over-eating obese model with hyperphagia, hyperinsulinemia, reduced growth hormone (GH), and insulin resistance. Dapagliflozin improved the metabolic and hormonal parameters in MC4R KO mice. MC4R KO female mice were treated with dapagliflozin for 14 weeks from 14-week age. Age-matched WT littermates and non-treated MC4R KO mice were used as control groups. Food intake was measured daily. Body weight was measured twice a week. Estrous cycles, GH, and luteinizing hormone (LH) profiles were measured. Selected tissues were collected at the end of experiments for gene expression profiles and hematoxylin–eosin staining. Regularity and mode of hormonal profiles were restored by the dapagliflozin treatment. Estrous cycle was partially normalized, number of CL was significantly increased, and the expression of Kiss1 and Gnrh1 in the hypothalamus and LH in the pituitary was markedly increased by the dapagliflozin treatment. It is conclsuded that dapagliflozin may recover LH and GH profiles partially through modification of relevant gene expression in the hypothalamus and pituitary, and result in an improved ovulation rate in obese mouse model. Dapagliflozin may therefore improve fertility in obese patients.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© Society for Endocrinology 2022
Page(s):
12
Article Type:
Research Article
Received Date:
09 Apr 2022
Accepted Date:
16 May 2022
Print Publication Date:
01 Aug 2022
Online Publication Date:
17 Jun 2022
Keywords:
SGLT2 inhibitor; infertility; obesity; ovulation; luteinizing hormone

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