Maternal hypoglycaemia throughout gestation until gestation day (GD)20 delays foetal growth and skeletal development. While partially prevented by return to normoglycaemia after completed organogenesis (GD17), underlying mechanisms are not fully understood. Here, we investigated the pathogenesis of these changes and significance of maternal hypoglycaemia extending beyond organogenesis in non-diabetic rats. Pregnant rats received insulin-infusion until GD20 or GD17, with sacrifice on GD20. Hypoglycaemia throughout gestation increased maternal corticosterone levels, which correlated with foetal levels. Growth plates displayed central histopathologic changes comprising disrupted cellular organisation, hypertrophic chondrocytes, and decreased cellular density; expression of pro-angiogenic factors, HIF-1α and VEGF-A increased in surrounding areas. Disproportionately decreased growth plate zone volumes and lower expression of the structural protein MATN-3 were seen, while bone ossification parameters were normal. Ending maternal/foetal hypoglycaemia on GD17 reduced incidence and severity of histopathologic changes and with normal growth plate volume. Compromised foetal skeletal development following maternal hypoglycaemia throughout gestation is hypothesised to result from corticosterone-induced hypoxia in growth plates, where hypoxia disrupts chondrocyte maturation and growth plate structure and volume, decreasing long bone growth. Maternal/foetal hypoglycaemia lasting only until GD17 attenuated these changes, suggesting a pivotal role of glucose in growth plate development.

整个妊娠期直至孕期（GD）20的孕妇低血糖症都会延迟胎儿的生长和骨骼发育。虽然在完成器官发生（GD17）后恢复正常血糖可部分预防，但尚不完全了解其潜在机制。在这里，我们调查了这些变化的发病机理，以及在非糖尿病大鼠中母体低血糖症超出器官发生的意义。妊娠大鼠接受胰岛素输注直至GD20或GD17，并在GD20上牺牲。整个妊娠期间的低血糖会增加孕妇的皮质酮水平，这与胎儿水平相关。生长板显示出中心的组织病理学变化，包括细胞组织破坏，肥大软骨细胞和细胞密度降低。周围区域促血管生成因子，HIF-1α和VEGF-A的表达增加。观察到生长板区体积减少得不成比例，结构蛋白MATN-3的表达降低，而骨化参数正常。终止GD17的母体/胎儿低血糖症可降低组织病理学改变的发生率和严重性，并且生长板体积正常。据推测，整个孕期孕妇低血糖后胎儿骨骼发育受损是由于皮质酮诱导的生长板缺氧所致，其中缺氧会破坏软骨细胞的成熟以及生长板的结构和体积，从而减少长骨生长。母体/胎儿低血糖症仅持续到GD17减弱了这些变化，提示葡萄糖在生长板发育中起关键作用。而骨化参数正常。终止GD17的母体/胎儿低血糖症可降低组织病理学改变的发生率和严重性，并且生长板体积正常。据推测，整个孕期孕妇低血糖后胎儿骨骼发育受损是由于皮质酮诱导的生长板缺氧所致，其中缺氧会破坏软骨细胞的成熟以及生长板的结构和体积，从而减少长骨生长。母体/胎儿低血糖症仅持续到GD17减弱了这些变化，提示葡萄糖在生长板发育中起关键作用。而骨化参数正常。终止GD17的母体/胎儿低血糖症可降低组织病理学改变的发生率和严重性，并且生长板体积正常。据推测，整个孕期孕妇低血糖后胎儿骨骼发育受损是由于皮质酮诱导的生长板缺氧所致，其中缺氧会破坏软骨细胞的成熟以及生长板的结构和体积，从而减少长骨生长。母体/胎儿低血糖症仅持续到GD17减弱了这些变化，提示葡萄糖在生长板发育中起关键作用。据推测，整个孕期孕妇低血糖后胎儿骨骼发育受损是由于皮质酮诱导的生长板缺氧所致，其中缺氧会破坏软骨细胞的成熟以及生长板的结构和体积，从而减少长骨生长。母体/胎儿低血糖症仅持续到GD17减弱了这些变化，提示葡萄糖在生长板发育中起关键作用。据推测，整个孕期孕妇低血糖后胎儿骨骼发育受损是由于皮质酮诱导的生长板缺氧所致，其中缺氧会破坏软骨细胞的成熟以及生长板的结构和体积，从而减少长骨生长。母体/胎儿低血糖症仅持续到GD17减弱了这些变化，提示葡萄糖在生长板发育中起关键作用。