Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, No. 17 Section 3 Renmin South Road, Chengdu, 610041, China.
Reproductive Endocrinology and Regulation Joint Laboratory, West China Second University Hospital, Sichuan University, 17 Section 3 Renmin South Road, Chengdu, 610041, People's Republic of China.
Reprod Sci. 2020 Sep;27(9):1752-1757. doi: 10.1007/s43032-020-00169-8. Epub 2020 Feb 21.
The incidence of diabetes in women of childbearing age has been increasing recently and implantation failure and early abortion are important reasons for infertility in diabetic women. Glycogen synthesis and decomposition are the cores of glucose homeostasis in endometrium and AMPK is activated when cellular energy consumption increases. Embryo implantation is a complex process required huge energy. Yet the changes of glucose metabolism in endometrium and its impact on embryo implantation in diabetic women are still unclear. In this research, we established diabetic pregnancy mice model by intraperitoneal injecting streptozotocin on pregnant day 1. We first tested the changes of endometrial glucose homeostasis and embryo implantation. Next, we demonstrated abnormal activation of AMPK in the endometrium of diabetic mice and its affecting endometrial glucose homeostasis. Finally, we compared the endometrial glucose homeostasis and embryo implantation outcome in diabetic pregnant mice treated with insulin or insulin combined with metformin. The results indicated that there was disturbed glucose homeostasis associated with excessive activation of AMPK in endometrium of diabetic pregnant mice. AMPK inhibitor improved the over-activation of AMPK pathway in the endometrium, meanwhile, partially corrected the abnormal glycogen metabolism and improved the implantation. Insulin improved the disorder of endometrial glucose homeostasis and implantation of diabetic mice. Our research explores the causes of high abortion and infertility rate in diabetic women which is to provide a therapeutic reference for patients with diabetes complicated with infertility and early abortion.
近年来，育龄期女性糖尿病的发病率不断上升，而着床失败和早期流产是糖尿病女性不孕的重要原因。糖原的合成与分解是子宫内膜葡萄糖稳态的核心，当细胞能量消耗增加时，AMPK 被激活。胚胎着床是一个需要大量能量的复杂过程。然而，糖尿病女性子宫内膜中葡萄糖代谢的变化及其对胚胎着床的影响仍不清楚。在这项研究中，我们通过在妊娠第 1 天腹腔注射链脲佐菌素建立了糖尿病妊娠小鼠模型。我们首先检测了子宫内膜葡萄糖稳态和胚胎着床的变化。接下来，我们证明了糖尿病小鼠子宫内膜中 AMPK 的异常激活及其对子宫内膜葡萄糖稳态的影响。最后，我们比较了胰岛素或胰岛素联合二甲双胍治疗的糖尿病妊娠小鼠的子宫内膜葡萄糖稳态和胚胎着床结果。结果表明，糖尿病妊娠小鼠子宫内膜存在葡萄糖稳态紊乱，与 AMPK 过度激活有关。AMPK 抑制剂改善了子宫内膜中 AMPK 通路的过度激活，同时部分纠正了异常的糖原代谢，改善了着床。胰岛素改善了糖尿病小鼠子宫内膜葡萄糖稳态和着床的紊乱。我们的研究探讨了糖尿病女性流产率和不孕率高的原因，为患有糖尿病合并不孕和早期流产的患者提供了治疗参考。
