Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore.
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore 117609, Singapore.
Int J Mol Sci. 2022 Aug 4;23(15):8685. doi: 10.3390/ijms23158685.
Pregnancy complications such as maternal hyperglycemia increase perinatal mortality and morbidity, but risks are higher in males than in females. We hypothesized that fetal sex-dependent differences in placental palmitic-acid (PA) and oleic-acid (OA) metabolism influence such risks. Placental explants ( = 22) were incubated with isotope-labeled fatty acids (C-PA or C-OA) for 24 or 48 h and the production of forty-seven C-PA lipids and thirty-seven C-OA lipids quantified by LCMS. Linear regression was used to investigate associations between maternal glycemia, BMI and fetal sex with C lipids, and between C lipids and birthweight centile. Placental explants from females showed greater incorporation of C-OA and C-PA into almost all lipids compared to males. Fetal sex also influenced relationships with maternal glycemia, with many C-OA and C-PA acylcarnitines, C-PA-diacylglycerols and C-PA phospholipids positively associated with glycemia in females but not in males. In contrast, several C-OA triacylglycerols and C-OA phospholipids were negatively associated with glycemia in males but not in females. Birthweight centile in females was positively associated with six C-PA and three C-OA lipids (mainly acylcarnitines) and was negatively associated with eight C-OA lipids, while males showed few associations. Fetal sex thus influences placental lipid metabolism and could be a key modulator of the impact of maternal metabolic health on perinatal outcomes, potentially contributing toward sex-specific adaptions in which females prioritize survival.
妊娠并发症，如母体高血糖，会增加围产期的死亡率和发病率，但男性的风险高于女性。我们假设胎儿性别依赖的胎盘棕榈酸（PA）和油酸（OA）代谢差异会影响这些风险。胎盘组织（n = 22）在同位素标记的脂肪酸（C-PA 或 C-OA）孵育 24 或 48 小时后，通过 LCMS 定量分析 47 种 C-PA 脂质和 37 种 C-OA 脂质。线性回归用于研究母体血糖、BMI 和胎儿性别与 C 脂质之间的关系，以及 C 脂质与出生体重百分位数之间的关系。与男性相比，女性胎盘组织对 C-OA 和 C-PA 的掺入量更大，几乎所有脂质都有增加。胎儿性别也影响与母体血糖的关系，许多 C-OA 和 C-PA 酰基辅酶 A、C-PA 二酰基甘油和 C-PA 磷脂与女性的血糖呈正相关，但与男性无关。相反，一些 C-OA 三酰基甘油和 C-OA 磷脂与男性的血糖呈负相关，但与女性无关。女性的出生体重百分位数与 6 种 C-PA 和 3 种 C-OA 脂质（主要是酰基辅酶 A）呈正相关，与 8 种 C-OA 脂质呈负相关，而男性则很少有相关性。因此，胎儿性别会影响胎盘脂质代谢，可能是母体代谢健康对围产期结局影响的关键调节因素，这可能有助于女性优先生存的性别特异性适应。
