雌性母鼠高脂肪暴露对子代糖脂代谢、卵巢功能的影响及与多囊卵巢综合征发病的关系研究

Effects of maternal high-fat diet exposure on glycolipid metabolism and ovarian function and its relationship with polycystic ovary syndrome in female offspring rats

摘要:

目的 研究雌性母鼠高脂肪暴露对子代小鼠糖、脂代谢，卵巢功能的影响及与多囊卵巢综合征（PCOS）发病的关系。方法 将45只受孕SD鼠根据随机数字表法分为宫内高脂肪膳食组（HFI组）、宫内及哺乳期高脂肪膳食组（HFII组）和正常膳食组（NC组），各15例。比较各组子代各阶段阴道涂片在性周期中占比，空腹血糖（FBG），空腹胰岛素（FINS），胰岛素敏感指数（ISI），胰岛素抵抗指数（HOMA-IR），甘油三酯（TG），静脉糖耐量试验（IPGTT），胰岛素释放试验（IRT）结果，卵巢形态学与脏器指数，动情间期生殖内分泌水平［雌激素（E2）、孕激素（P）、促黄体生成素（LH）、睾酮（T）］，采用Logistic多元回归分析PCOS发生的影响因素。结果 HFI组、HFII组动情期较NC组长（P <0.05），HFII组较HFI组长（P <0.05）。HFI组、HFII组FBG、FINS、HOMA-IR、TG水平较NC组高，ISI较NC组低（P <0.05）；HFII组FBG、FINS、HOMA-IR、TG水平较HFI组高，ISI较HFI组低（P <0.05）。各组血糖、胰岛素比较，差异有统计学意义（P <0.05）。HFI组、HFII组雌仔卵巢脏器系数较NC组大，且HFII较HFI组大（P <0.05）。HFI组、HFII组血清E2、LH较NC组低，血清T较NC组高（P <0.05），HFII组血清E2、LH较HFI组低，血清T较HFI组高（P <0.05），各组雌仔血清P比较，差异无统计学意义（P >0.05）。HFI组、HFII组雌仔3β-HSD1、3β-HSD2、3β-HSD5、17β-HSD1及5ɑ-R1 mRNA较NC组高（P <0.05），HFII组较HFI组高（P <0.05）。经多因素一般Logistic回归分析，E2水平［O=0.381（95% CI：0.339，0.428）］是PCOS的保护因素，FBG［O=2.740（95% CI：1.743，4.306）］、TG［O=3.527（95% CI：2.116，5.879）］及T水平［O=1.337（95 %CI：1.294，1.381）］是PCOS的危险因素。结论 高脂肪饮食暴露可引起子代糖、脂代谢异常，并造成卵巢形态、功能改变，是子代发生PCOS的相关危险因素，其机制可能与调控雄激素转化酶的表达有关。

Abstract:

Objective To study the effects of maternal high-fat diet exposure on glycolipid metabolism and ovarian function and its relationship with polycystic ovary syndrome (PCOS) in female offspring rats.Methods Forty-five Sprague-Dawley (SD) pregnant female rats were selected and divided into high-fat diet during pregnancy group (HFI group, n = 15), high-fat diet during pregnancy and lactation group (HFII group, n = 15) and normal diet group (NC group, n = 15). The proportion of cells of each stage of sexual cycle in vaginal smears, fasting blood glucose (FBG), fasting insulin (FINS), insulin sensitivity index (ISI), insulin resistance index (HOMA-IR), triglyceride (TG), intraperitoneal glucose tolerance test (IPGTT), insulin release test (IRT), ovarian morphology and organ index, and the levels of serum reproductive endocrine indicators [estrogen (E2), progesterone (P), luteinizing hormone (LH), and testosterone (T)] during anoestrum in the female offspring were detected. Multivariate Logistic regression model was used to analyze the factors affecting the occurrence of PCOS.Results Compared with female offspring rats of NC group, female offspring rats of HFI group and HFII group had longer estrus (P < 0.05), while female offspring rats of HFII group had longer estrus than those of HFI group (P < 0.05). The levels of FBG, FINS, HOMA-IR, and TG in the female offspring rats of HFI and HFII groups were higher, and the ISI was lower in comparison to female offspring rats of NC group (P < 0.05); the levels of FBG, FINS, HOMA-IR and TG were higher but ISI was lower in female offspring rats of HFII group compared with female offspring rats of HFI group (P < 0.05). There were significant differences in blood glucose and insulin among the female offspring rats of distinct groups (P < 0.05). The organ index of ovary of female offspring was greater in HFI group and HFII group than that in NC group, and that in HFII group was even greater compared with HFI group (P < 0.05). The serum E2 and LH in the female offspring rats of the HFI group and HFII group were lower, but the serum T was higher in comparison to female offspring rats of NC group (P < 0.05); the serum levels of E2 and LH were lower whereas serum T level was higher in the female offspring rats of HFII group than those in the female offspring rats of HFI group (P < 0.05). Besides, compared with the female offspring rats of NC group, the 3β-HSD1, 3β-HSD2, 3β-HSD5, 17β-HSD1, and 5ɑ-R1 mRNA were higher in the female offspring rats of HFI group and HFII group (P < 0.05), while those in female offspring rats of HFII group were higher compared with female offspring rats of HFI group (P < 0.05). Multivariate Logistic regression analysis suggested that E2 level [R = 0.381 (95% CI: 0.339, 0.428)] was a protective factor for PCOS, whereas FBG level [R = 2.740 (95% CI: 1.734, 4.306)], TG level [R = 3.527 (95% CI: 2.116, 5.879)], and T level [R = 1.337 (95% CI: 1.294, 1.381)] were risk factors for PCOS in female offspring rats (P < 0.05).Conclusions Exposure to a high-fat diet can cause abnormal glucose and lipid metabolism and changes in ovarian morphology and function of emale offspring rats. Thus, maternal high-fat diet exposure is a risk factor for emale offspring PCOS, and its mechanism may be related to the dysregulation of androgen-converting enzymes.