Department of Nutrition, Texas A&M University, College Station, Texas.
Department of Pathology, Princeton Medical Center, Plainsboro, New Jersey; Department of Biological Sciences, Rutgers University, Newark, New Jersey.
Lab Invest. 2023 Jan;103(1):100017. doi: 10.1016/j.labinv.2022.100017.
FoxO1 is an important transcriptional factor that regulates cell survival and metabolism in many tissues. Deleting FoxO1 results in embryonic death due to failure of chorioallantoic fusion at E8.5; however, its role in placental development during mid-late gestation is unclear. In both human patients with gestational diabetes and pregnant mice with hyperglycemia, placental FoxO1 expression was significantly increased. Using FoxO1+/- mice, the effects of FoxO1 haploinsufficiency on placental development under normoglycemia and hyperglycemia were investigated. With FoxO1 haploinsufficiency, the term placental weight increased under both normal and hyperglycemic conditions. Under normoglycemia, this weight change was associated with a general enlargement of the labyrinth, along with increased cell proliferation, decreased cell apoptosis, and decreased expression of p21, p27, Casp3, Casp8, and Rip3. However, under hyperglycemia, the placental weight change was associated with increased fetal blood space, VEGFA overexpression, and expression changes of the angiogenic markers, Eng and Tsp1. In conclusion, FoxO1 plays a role in regulating cell proliferation, cell survival, or angiogenesis, depending on blood glucose levels, during placenta development.
FoxO1 是一种重要的转录因子，可调节许多组织中的细胞存活和代谢。在 E8.5 时，由于绒毛膜尿囊融合失败，FoxO1 的缺失会导致胚胎死亡；然而，其在妊娠中期至晚期胎盘发育中的作用尚不清楚。在患有妊娠糖尿病的人类患者和患有高血糖症的妊娠小鼠中，胎盘 FoxO1 的表达显著增加。利用 FoxO1+/- 小鼠，研究了 FoxO1 单倍不足对正常血糖和高血糖下胎盘发育的影响。FoxO1 单倍不足时，正常和高血糖条件下的足月胎盘重量增加。在正常血糖条件下，这种体重变化与胎盘绒毛膜腔的普遍增大有关，同时伴随着细胞增殖增加、细胞凋亡减少以及 p21、p27、Casp3、Casp8 和 Rip3 的表达减少。然而，在高血糖条件下，胎盘重量的变化与胎儿血腔增加、VEGFA 过表达以及血管生成标记物 Eng 和 Tsp1 的表达变化有关。总之，FoxO1 在胎盘发育过程中根据血糖水平调节细胞增殖、细胞存活或血管生成。
