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.

肥胖是女性不孕的主要原因，能量摄入与生殖功能障碍直接相关。为了探索潜在的机制，研究人员对喂食高脂肪饮食 20 周的雌性 Wistar 大鼠进行了生殖健康和肠促胰岛素/生殖激素受体表达的干扰研究。监测代谢参数和卵巢/肾上腺基因表达以及发情周期和交配时的生育力。高脂肪喂养显着增加体重、血浆胰岛素和 HOMA-IR，表明肥胖和胰岛素抵抗。与正常饲料喂养的大鼠相比，发情周期延长，50%的大鼠平均周期长度≥7天。生殖结果显示，高脂肪饮食使窝产仔数减少 48%，其中 16% 的大鼠无法怀孕。此外，80% 的高脂肪组怀孕时间超过 35 天，而正常饮食组的这一比例为 33%。此外，高脂肪喂养的老鼠生下的幼崽有 35% 被母亲吃掉或出生时死亡，而对照组老鼠则没有观察到这一情况。这些变化与卵巢中 Amh、Npy2R 和 GcgR 基因表达的下调以及 InsR 和 Glp-1R 基因的上调有关。在肾上腺中，Glp-1R、GipR、Npy2R、InsR、GcgR、GshR 和 Esr-1 基因上调。高脂肪饮食的卵巢和肾上腺的组织学分析显示形态发生变化，囊肿数量显着增加，肾上腺包膜厚度减少。高脂肪组的胰岛素、睾酮和黄体酮的循环水平显着升高，血浆中 FSH 水平降低。这些数据表明，高脂肪喂养会破坏女性生殖功能，并表明肠道与卵巢和肾上腺生殖激素之间存在重要的相互作用，值得进一步研究。