Department of Pediatrics, Section of Diabetes and Endocrinology, Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Department of Pediatrics, Biomedical and Behavioral Methodology Core, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Placenta. 2017 Sep;57:26-32. doi: 10.1016/j.placenta.2017.06.001. Epub 2017 Jun 6.
Abnormal placental function in maternal diabetes affects fetal health and can predispose offspring to metabolic diseases in later life. There are fetal sex-specific differences in placenta structure and gene expression, which may affect placental responses to maternal diabetes. The present study examined the effects of maternal diabetes on indices of mitochondrial biogenesis in placentae from male and female offspring. Mitochondrial DNA (mtDNA) copy number and expression of key regulators of mitochondrial biogenesis were assessed in placentae from 19 diabetic and 23 non-diabetic women. The abundance of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and mitochondria transcription factor A (TFAM) were lower in female placentae compared to males, but not mtDNA content. In male offspring, maternal diabetes was associated with decreased placental PGC-1α and TFAM, and mitochondrial DNA (mtDNA) content. Male placental TFAM levels were highly correlated with PGC-1α and mtDNA content. However, despite decreased PGC-1α, concomitant changes in TFAM and mtDNA content by diabetes were not observed in females. In addition, TFAM abundance in female placentae was not correlated with PGC-1α or mtDNA content. In summary, placental PGC-1α/TFAM/mitochondrial biogenesis pathway is affected by maternal diabetes and offspring sex. Decreased PGC-1α in response to maternal diabetes plausibly contributes to impaired mitochondrial biogenesis in placentae of male offspring, which may affect long-term health and explain some of enhanced risk of future metabolic diseases in males.
母体糖尿病导致的胎盘功能异常会影响胎儿健康，并使后代在以后的生活中易患代谢疾病。胎盘的结构和基因表达存在胎儿性别特异性差异，这可能会影响胎盘对母体糖尿病的反应。本研究探讨了母体糖尿病对雄性和雌性后代胎盘中线粒体生物发生指标的影响。在 19 名糖尿病妇女和 23 名非糖尿病妇女的胎盘组织中，评估了线粒体 DNA(mtDNA)拷贝数和线粒体生物发生关键调节因子的表达。与男性相比，女性胎盘中的过氧化物酶体增殖物激活受体-γ共激活因子 1α(PGC-1α)和线粒体转录因子 A(TFAM)的丰度较低，但 mtDNA 含量没有差异。在雄性后代中，母体糖尿病与胎盘 PGC-1α和 TFAM以及线粒体 DNA(mtDNA)含量减少有关。雄性胎盘 TFAM 水平与 PGC-1α和 mtDNA 含量高度相关。然而，尽管 PGC-1α 减少，但糖尿病并未导致女性胎盘 TFAM 和 mtDNA 含量发生相应变化。此外，女性胎盘 TFAM 的丰度与 PGC-1α或 mtDNA 含量无关。总之，母体糖尿病和后代性别会影响胎盘 PGC-1α/TFAM/线粒体生物发生途径。母体糖尿病导致的 PGC-1α 减少可能导致雄性后代胎盘中线粒体生物发生受损，这可能会影响长期健康，并解释男性未来代谢疾病风险增加的部分原因。
