Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, Zhejiang, China.
Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences (No. 2019RU056), Shanghai, China.
Biol Reprod. 2022 Jul 25;107(1):148-156. doi: 10.1093/biolre/ioac138.
The prevalence of gestational diabetes mellitus (GDM) is increasing rapidly. In addition to the metabolic disease risks, GDM might increase the risks of cryptorchidism in children. However, its mechanism involved in abnormalities of the male reproductive system is still unclear. The purpose of this study was to study the effects of GDM on the development of mouse fetal Leydig cells (FLCs) and Sertoli cells (SCs). Pregnant mice were treated on gestational days 6.5 and 12.5 with streptozotocin (100 mg/kg) or vehicle (sodium citrate buffer). Leydig cell and SC development and functions were evaluated by investigating serum testosterone levels, cell number and distribution, genes, and protein expression. GDM decreased serum testosterone levels, the anogenital distance, and the level of desert hedgehog in SCs of testes of male offspring. FLC number was also decreased in testes of GDM offspring by delaying the commitment of stem Leydig cells into the Leydig cell lineage. RNA-seq showed that FOXL2, RSPO1/β-catenin signaling was activated and Gsk3β signaling was inhibited in GDM offspring testis. In conclusion, GDM disrupted reproductive tract and testis development in mouse male offspring via altering genes related to development.
妊娠期糖尿病（GDM）的患病率正在迅速上升。除了代谢疾病风险外，GDM 可能会增加儿童隐睾的风险。然而，其涉及男性生殖系统异常的机制尚不清楚。本研究旨在研究 GDM 对小鼠胎睾间质细胞（FLC）和支持细胞（SCs）发育的影响。在妊娠第 6.5 天和 12.5 天，用链脲佐菌素（100mg/kg）或载体（柠檬酸钠缓冲液）处理怀孕的小鼠。通过研究血清睾酮水平、细胞数量和分布、基因和蛋白表达来评估 Leydig 细胞和 SC 的发育和功能。GDM 降低了雄性后代睾丸中血清睾酮水平、肛殖距和沙漠刺猬在 SC 中的水平。GDM 后代的 FLC 数量也减少了，这是通过延迟干细胞 Leydig 细胞向 Leydig 细胞谱系的分化而导致的。RNA-seq 显示，GDM 后代睾丸中 FOXL2 和 RSPO1/β-catenin 信号被激活，Gsk3β 信号被抑制。总之，GDM 通过改变与发育相关的基因，破坏了雄性子代生殖道和睾丸的发育。
