Department of Animal Science, Iowa State University, Ames, Iowa, USA.
Department of Obstetrics, Gynecology, and Women's Health, University of Missouri, Columbia, Missouri, USA.
Biol Reprod. 2019 Oct 25;101(4):771-781. doi: 10.1093/biolre/ioz116.
Gestational diabetes mellitus (GDM) is an obstetric disorder affecting approximately 10% of pregnancies. The four high-fat, high-sucrose (HFHS) mouse model emulates GDM in lean women. Dams are fed a HFHS diet 1 week prior to mating and throughout gestation resulting in inadequate insulin response to glucose in mid-late pregnancy. The offspring of HFHS dams have increased adiposity, thus, we hypothesized that maternal metabolic alterations during lean GDM would compromise ovarian function in offspring both basally and in response to a control or HFHS diet in adulthood. Briefly, DLPL were lean dams and control diet pups; DLPH were lean dams and HFHS pups; DHPL were HFHS dams and control diet pups; and DHPH were HFHS dams and HFHS pups. A HFHS challenge in the absence of maternal GDM (DLPL vs. DLPH) increased 3 and decreased 30 ovarian proteins. Maternal GDM in the absence of a dietary stress (DLPL vs. DHPL) increased abundance of 4 proteins and decreased abundance of 85 proteins in the offspring ovary. Finally, 87 proteins increased, and 4 proteins decreased in offspring ovaries due to dietary challenge and exposure to maternal GDM in utero (DLPL vs. DHPH). Canopy FGF signaling regulator 2, deleted in azoospermia-associated protein 1, septin 7, and serine/arginine-rich splicing factor 2 were altered across multiple offspring groups. Together, these findings suggest a possible impact on fertility and oocyte quality in relation to GDM exposure in utero as well as in response to a western diet in later life.
妊娠期糖尿病（GDM）是一种影响约 10%妊娠的产科疾病。四种高脂肪、高蔗糖（HFHS）的小鼠模型模拟了瘦女性的 GDM。母鼠在交配前一周和整个妊娠期内都喂食 HFHS 饮食，导致妊娠中期和晚期对葡萄糖的胰岛素反应不足。HFHS 母鼠的后代肥胖增加，因此，我们假设瘦 GDM 期间的母体代谢改变会损害后代的卵巢功能，无论是在基础水平还是在成年后对对照或 HFHS 饮食的反应中。简而言之，DLPL 是瘦母鼠和对照饮食的幼鼠；DLPH 是瘦母鼠和 HFHS 幼鼠；DHPL 是 HFHS 母鼠和对照饮食的幼鼠；DHPH 是 HFHS 母鼠和 HFHS 幼鼠。在没有母体 GDM（DLPL 与 DLPH）的情况下，HFHS 挑战增加了 3 种和减少了 30 种卵巢蛋白。在没有饮食压力的情况下，母体 GDM（DLPL 与 DHPL）增加了 4 种蛋白质的丰度，减少了 85 种蛋白质的丰度。最后，由于宫内饮食挑战和母体 GDM 暴露，87 种蛋白质在后代卵巢中增加，4 种蛋白质减少（DLPL 与 DHPH）。冠层 FGF 信号调节剂 2、无精子症相关蛋白 1 缺失、间隔 7 和丝氨酸/精氨酸富含剪接因子 2 在多个后代群体中发生改变。这些发现表明，在宫内暴露于 GDM 以及在以后的生活中对西方饮食的反应中，可能对生育能力和卵母细胞质量产生影响。
