Core Insights - The article discusses the impact of intrauterine hyperglycemia (IUHG) on the development of primordial germ cells (PGC) and fertility, particularly emphasizing its detrimental effects on female offspring [2][5][8] - A recent study published in Cell Discovery reveals that IUHG disrupts sex-specific epigenetic reprogramming during PGC development, leading to reproductive health issues and intergenerational effects [2][8] Group 1: Research Findings - IUHG significantly disrupts the development of PGCs, with a more pronounced effect on female offspring, resulting in reduced fertility [5][8] - The study utilized transgenic mice exposed to high glucose environments to systematically investigate the effects of IUHG on PGC development, revealing that IUHG affects chromatin accessibility and DNA methylation reprogramming in a sex-specific manner [5][6] Group 2: Mechanisms of Impact - In female embryos, IUHG leads to abnormal retention of chromatin accessibility at pluripotency gene promoters, inhibiting normal gene silencing and blocking the initiation of meiosis, ultimately hindering oocyte maturation [6][8] - In contrast, male embryos experience less severe effects on chromatin accessibility and gene transcription, but global DNA methylation reprogramming is impaired, particularly in key imprinted gene regions, indicating potential developmental impacts on future generations [6][8] Group 3: Implications and Future Directions - The findings underscore the importance of blood sugar management during pregnancy and suggest new avenues for improving reproductive health in offspring through metabolic intervention or epigenetic regulation [8]

Core Viewpoint - The article discusses the safety concerns and recommendations regarding the use of GLP-1 medications during pregnancy and breastfeeding, highlighting the need for caution and further research in this area [1][3]. Group 1: Research on GLP-1 Medications and Pregnancy - A large study published in January 2024 in JAMA Internal Medicine tracked around 50,000 children born to mothers with type 2 diabetes who used GLP-1 or insulin in early pregnancy, finding no increased risk of congenital defects compared to insulin use [5]. - Another study published in 2023 reviewed 39 independent studies on the effects of GLP-1 agonists and SGLT2 inhibitors during pregnancy and breastfeeding, concluding that there is extremely limited information on their safety [6]. Group 2: Risks Associated with GLP-1 Use During Pregnancy - Potential risks of GLP-1 medications during pregnancy may include miscarriage, low birth weight, and congenital defects, primarily due to their impact on maternal food intake and weight gain [6][7]. - Although concerns are mainly based on animal studies, the lack of human research has led to recommendations for discontinuation during pregnancy [7]. Group 3: Recommendations for Women Planning to Become Pregnant - Women are advised to stop using any GLP-1 medications at least two months before attempting to conceive, along with adopting additional preconception lifestyle measures [8]. - The American Diabetes Association recommends insulin as the preferred medication for managing diabetes during pregnancy, while other diabetes medications like metformin and glipizide are not first-line treatments due to their placental transfer [7][8]. Group 4: Breastfeeding Considerations - There is insufficient research to determine the safety of GLP-1 medications during breastfeeding, leading to recommendations against their use during this period [9][10].