Disturbed ovarian morphology, oestrous cycling and fertility of high fat fed rats are linked to alterations of incretin receptor expression

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Obesity is a major cause of infertility in females with a direct correlation between energy intake and reproductive dysfunction. To explore underlying mechanisms, disturbances in reproductive health and incretin/reproductive hormone receptor expression were studied in female Wistar rats fed a high-fat-diet for 20-weeks. Metabolic parameters and ovarian/adrenal gene expression were monitored along with estrous cycling and fertility upon mating. High-fat-feeding significantly increased body weight, plasma insulin and HOMA-IR, indicative of obesity and insulin resistance. Estrous cycles were prolonged compared to normal chow-fed rats, with 50 % having an average cycle length ≥ 7days. Reproductive outcomes revealed high-fat-diet reduced litter size by 48 %, with 16 % rats unable to achieve pregnancy. Furthermore, 80 % of the high-fat group took > 35 days to become pregnant compared to 33 % fed a normal-diet. Also, 35 % of pups born to high-fat-fed rats were eaten by mothers or born dead which was not observed with control rats. These changes were associated with downregulation of Amh, Npy2R and GcgR gene expression in ovaries with upregulation of InsR and Glp-1R genes. In adrenals, Glp-1R, GipR, Npy2R, InsR, GcgR, GshR and Esr-1 genes were upregulated. Histological analysis of high-fat-diet ovaries and adrenals revealed changes in morphology with significantly increased number of cysts and reduced adrenal capsule thickness. Circulating levels of insulin, testosterone and progesterone was significantly higher in high-fat group with reduced FSH levels in plasma. These data demonstrate that high-fat feeding disrupts female reproductive function and suggest important interactions between gut and reproductive hormones in ovaries and adrenals which merit further investigation.

Original languageEnglish
Article number100784
Pages (from-to)1-9
Number of pages9
JournalReproductive biology
Issue number3
Early online date19 Jun 2023
Publication statusPublished (in print/issue) - 1 Sept 2023

Bibliographical note

Funding Information:
These studies were supported by Diabetes UK RDLF grant to RCM Ulster University Vice-Chancellor Research Scholarship studentship awarded to AS and Ulster University Selective Research Funding. The authors thank University of Virginia Centre for Research in Reproduction Ligand Assay and Analysis Core which is supported by the Eunice Kennedy Shriver NICHD/NIH Grant R24HD102061 for measurement of reproductive hormones.

Publisher Copyright:
© 2023 The Authors


  • Adrenal
  • High fat diet
  • Incretin
  • Infertility
  • Ovary


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