Endocrine Abstracts

Background/Aims: Emerging evidence suggests that gut hormones interact with the reproductive axis and impact fertility in females. Here we combine three major gut hormones glucose-dependent insulinotropic peptide (GIP), glucagon (GCG) and glucagon-like peptide-1 (GLP-1), as a triple-agonist (TA) to elucidate its effects on female reproductive function.

Methods: Female Swiss TO-mice (n = 6) on high-fat diet (HFD) or normal diet (ND) for 18-weeks received twice-daily intraperitoneal injections of TA at 25 nmol/kg bw or saline vehicle (0.9% (w/v) NaCl) for 21 days. Metabolic and reproductive parameters were regularly monitored. Terminal samples were collected for hormone measurement and analysis.

Results: TA significantly decreased body weight (P < 0.05) and blood glucose (P < 0.01) compared to HFD mice. Cumulative energy intake reduced (P < 0.01 to P < 0.001) on days 7 and 14 in the TA group compared to HFD mice. Only 16% of TA mice had abnormally prolonged estrus phase compared to 25% HFD mice. While proestrus frequency decreased (P < 0.01) with HFD, TA increased (P < 0.05 and P < 0.001) proestrus frequency compared to ND and HFD mice. TA also reduced metestrus (P < 0.01) and diestrus (P < 0.05) frequencies compared to HFD and ND controls respectively. There was a significant (P < 0.05) increase in plasma LH in the HFD group but no changes in LH, FSH, progesterone or corticosterone after TA administration. GIP and PYY were unaltered in plasma by TA but a decrease (P < 0.01) in GLP-1 was observed compared to ND and HFD mice. In the ovary, there was an increase (P < 0.05) in secondary follicles and corpus luteum numbers in the TA group. However, atretic follicles remained significantly (P < 0.05) higher in the TA and HFD groups compared to ND controls.

Conclusion: The above data highlight the importance of the reproductive effects of key gut hormones. Further understanding of these mechanisms will provide better options for the prevention of energy-related reproductive disorders.