Maternal obesity alters brain derived neurotrophic factor (BDNF) signaling in the placenta in a sexually dimorphic manner.
Maternal obesity alters brain derived neurotrophic factor (BDNF) signaling in the placenta in a sexually dimorphic manner.
复制标题
孕产妇肥胖以性二态性方式改变胎盘中的神经营养因子（BDNF）信号。
DOI：
10.1016/j.placenta.2016.11.010
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发表时间：
2017-01
期刊：
影响因子：
3.8
通讯作者：
Myatt L
中科院分区：
文献类型：
--
作者：
Prince CS;Maloyan A;Myatt L
肥胖是产科的一个主要临床问题，与不良妊娠结局和胎儿发育有关。脑源性神经营养因子 (BDNF) 是经过验证的 miR-210 靶标，对于胎盘发育、胎儿生长、葡萄糖代谢和能量稳态至关重要。肥胖者血浆 BDNF 水平降低；然而，胎盘 BDNF 尚未在孕产妇肥胖背景下进行研究。在这项研究中，我们研究了母亲肥胖和性别二态性对胎盘 BDNF 信号传导的影响。在无医疗并发症且通过剖宫产无分娩分娩的足月瘦（孕前 BMI < 25）和肥胖（孕前 BMI > 30）女性的胎盘中测量 BDNF 信号。通过 RT-PCR、ELISA 和 Western blot 检测 MiRNA-210、BDNF mRNA、proBDNF 和成熟 BDNF。使用蛋白质印迹测量通过 TRKB（BDNF 受体）的下游信号传导。母亲肥胖与女性胎儿胎盘中 miRNA-210 增加和 BDNF mRNA 减少以及男性胎儿胎盘中 proBDNF 减少有关。我们还发现，与女性胎儿相比，男性胎儿胎盘中的成熟 BDNF 有所减少。 Mir-210表达与成熟BDNF蛋白呈负相关。在肥胖女性的胎盘中，TRKB 在酪氨酸 817（而非酪氨酸 515）处磷酸化的程度增加。母亲肥胖与男性胎儿胎盘中 MAPK p38 磷酸化增加相关，但与 ERK p42/44 磷酸化无关。 BDNF 调节非常复杂且受到高度监管。孕前/早期产妇肥胖以性别二态性方式对胎盘中的 BDNF/TRKB 信号产生不利影响。这些数据共同表明，胎盘 TRKB 信号传导的诱导可以改善胎盘 OB 表型，从而改善围产期结局。
Obesity is a major clinical problem in obstetrics being associated with adverse pregnancy outcomes and fetal programming. Brain derived neurotrophic factor (BDNF), a validated miR-210 target, is necessary for placental development, fetal growth, glucose metabolism, and energy homeostasis. Plasma BDNF levels are reduced in obese individuals; however, placental BDNF has yet to be studied in the context of maternal obesity. In this study, we investigated the effect of maternal obesity and sexual dimorphism on placental BDNF signaling. BDNF signaling was measured in placentas from lean (pre-pregnancy BMI < 25) and obese (pre-pregnancy BMI>30) women at term without medical complications that delivered via cesarean section without labor. MiRNA-210, BDNF mRNA, proBDNF, and mature BDNF were measured by RT – PCR, ELISA, and Western blot. Downstream signaling via TRKB (BDNF receptor) was measured using Western blot. Maternal obesity was associated with increased miRNA-210 and decreased BDNF mRNA in placentas from female fetuses, and decreased proBDNF in placentas from male fetuses. We also identified decreased mature BDNF in placentas from male fetuses when compared to female fetuses. Mir-210 expression was negatively correlated with mature BDNF protein. TRKB phosphorylated at tyrosine 817, not tyrosine 515, was increased in placentas from obese women. Maternal obesity was associated with increased phosphorylation of MAPK p38 in placentas from male fetuses, but not phosphorylation of ERK p42/44. BDNF regulation is complex and highly regulated. Pre-pregnancy/early maternal obesity adversely affects BDNF/TRKB signaling in the placenta in a sexually dimorphic manner. These data collectively suggest that induction of placental TRKB signaling could ameliorate the placental OB phenotype, thus improving perinatal outcome.