Metformin Impacts Human Syncytiotrophoblast Mitochondrial Function from Pregnancies Complicated by Obesity and Gestational Diabetes Mellitus in a Sexually Dimorphic Manner.
Metformin Impacts Human Syncytiotrophoblast Mitochondrial Function from Pregnancies Complicated by Obesity and Gestational Diabetes Mellitus in a Sexually Dimorphic Manner.
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DOI：
10.3390/antiox12030719
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发表时间：
2023-03-14
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影响因子：
--
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母体肥胖和妊娠期糖尿病（GDM）与胎盘功能障碍、小于胎龄儿（SGA）后代和成人发病疾病的发生有关。我们研究了二甲双胍，通常用于治疗A2型GDM，如何影响胎盘代谢以及线粒体含量和功能。从在足月剖宫产时从瘦（孕前BMI < 25）、肥胖（BMI > 30）和肥胖A2 GDM妇女收集的男性和女性胎儿的胎盘制备合体滋养层细胞（STB）。STB的二甲双胍处理（0.001-10 mM）未引起非线粒体呼吸的变化，但基础、最大和ATP相关呼吸和备用容量的显著浓度依赖性（1和10 mM）降低。在低二甲双胍浓度下，男性A2 GDM胎盘STB中与质子泄漏相关的呼吸显著增加。二甲双胍浓度≥1 mM可增加瘦女性胎盘中STB的糖酵解，但仅改善女性STB的糖酵解能力。而二甲双胍对任何组的男性STB的超氧化物生成几乎没有影响，它使瘦和肥胖女性的女性STB的超氧化物生成呈浓度依赖性降低。随着二甲双胍浓度的增加，在肥胖女性的STB和瘦女性的男性STB中观察到较少的线粒体。二甲双胍以性别二态性方式影响STB线粒体功能，但浓度高于接受二甲双胍治疗GDM的女性母体循环中报告的浓度（约0.01 mM）。
Maternal obesity and gestational diabetes mellitus (GDM) are associated with placental dysfunction, small for gestational age (SGA) offspring, and programming of adult-onset disease. We examine how metformin, commonly used to treat type A2 GDM, affects placental metabolism as well as mitochondrial content and function. Syncytiotrophoblasts (STBs) were prepared from placentas of male and female fetuses collected at term cesarean section from lean (pre-pregnancy BMI < 25), obese (BMI > 30), and obese A2GDM women. Metformin treatment (0.001–10 mM) of STB caused no change in non-mitochondrial respiration but significant concentration-dependent (1 and 10 mM) decreases in basal, maximal, and ATP-linked respiration and spare capacity. Respiration linked to proton leak was significantly increased in STB of male A2GDM placentas at low metformin concentrations. Metformin concentrations ≥1 mM increased glycolysis in STB from placentas from lean women, but only improved glycolytic capacity in female STB. Whereas metformin had little effect on superoxide generation from male STB of any group, it gave a concentration-dependent decrease in superoxide generation from female STB of lean and obese women. Fewer mitochondria were observed in STB from obese women and male STB from lean women with increasing metformin concentration. Metformin affects STB mitochondrial function in a sexually dimorphic manner but at concentrations above those reported in maternal circulation (approximately 0.01 mM) in women treated with metformin for GDM.
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影响因子：
3.7
作者：
Le Moullec N;Fianu A;Maillard O;Chazelle E;Naty N;Schneebeli C;Gérardin P;Huiart L;Charles MA;Favier F
通讯作者：
Favier F
影响因子：
3.8
作者：
EIS, ALW;BROCKMAN, DE;MYATT, L
通讯作者：
MYATT, L
影响因子：
3.9
作者：
Eyal, Sara;Easterling, Thomas R.;Hebert, Mary F.
通讯作者：
Hebert, Mary F.
影响因子：
39.2
作者：
BRAY, GA
通讯作者：
BRAY, GA
影响因子：
--
作者：
Kelley KW;Carroll DG;Meyer A
通讯作者：
Meyer A