Intrauterine hyperglycemia impairs mouse primordial germ cell development and fertility by sex-specific epigenetic reprogramming interference by Jiangshan Cong & Qing Li & Yangyang Li & Minghao Li & Yan Shi & Peiran Hu & Xidi Yin & Qianyun Zhang & Jianzhong Sheng & Jinsong Li & Guolian Ding & Yu Zhang & Hefeng Huang instant download

Intrauterine hyperglycemia impairs mouse primordial germ cell development and fertility by sex-specific epigenetic reprogramming interference by Jiangshan Cong & Qing Li & Yangyang Li & Minghao Li & Yan Shi & Peiran Hu & Xidi Yin & Qianyun Zhang & Jianzhong Sheng & Jinsong Li & Guolian Ding & Yu Zhang & Hefeng Huang instant download

Adverse intrauterine environments, such as hyperglycemia, impair sexual reproduction and species continuity, yet the underlyingmechanisms remain poorly understood. In this study, we demonstrated that intrauterine hyperglycemia significantly disruptedprimordial germ cell (PGC) development, especially in female offspring, thus reducing fertility. Using Oct4-EGFP transgenic micewith intrauterine hyperglycemia exposure, we revealed that hyperglycemia compromised sexually specific chromatin accessibilityand DNA methylation reprogramming during PGC development. Particularly, in female PGCs, hyperglycemia leads to the aberrant1234567890();,:retention of chromatin accessibility at pluripotency gene promoters such as Nanog and Tfap2c, inhibiting proper gene silencing andblocking the initiation of meiosis, which ultimately hinders oocyte maturation. Conversely, male PGCs exhibit less severe changes inchromatin accessibility and gene transcription. Intriguingly, the global DNA methylation reconstruction is impaired in male PGCs,particularly in key imprinted gene regions, suggesting potential developmental ramifications for later stages and even subsequentgenerations. Particularly, our findings indicate that intrauterine hyperglycemia adversely affects sex differentiation in PGCs bydisrupting the expression of critical sex-determining transcription factors. Collectively, these findings highlight how intrauterinehyperglycemia interferes with sex-specific epigenetic reprogramming during PGC development, leading to abnormal germ celldevelopment, reduced fertility, and adverse intergenerational effects.Cell Discovery;