Placental mTOR Signaling and Sexual Dimorphism in Metabolic Health across the Lifespan of Offspring.
Placental mTOR Signaling and Sexual Dimorphism in Metabolic Health across the Lifespan of Offspring.
复制标题
DOI：
10.3390/children8110970
复制
发表时间：
2021-10-26
期刊：
影响因子：
--
通讯作者：
Alejandro EU
中科院分区：
文献类型：
--
作者：
Beetch M;Alejandro EU
在过去的几十年里，出现了强有力的证据，表明胎儿对成人疾病的编程。人类和临床前对宫内侮辱的研究报告了雷帕霉素机械靶点(MTOR)对胎盘营养感知的扰动。本文综述了与胎盘mTOR调控相关的妊娠并发症，如胎儿生长受限(FGR)、胎儿过度生长、妊娠期糖尿病(GDM)、多囊卵巢综合征(PCOS)、母体营养受限(MNR)、先兆子痫(PE)、母体吸烟及对子代出生体重的相关影响。讨论了mTOR相关的出生体重结果和后代代谢健康轨迹之间的联系，重点讨论了性别二型性。总结了人类生理学和动物模型，以便于深入理解。妊娠期糖尿病、多囊卵巢综合征和胎儿过度生长与胎盘mTOR增加有关，而FGR、MNR和母亲吸烟与胎盘mTOR活性降低有关。一般情况下，mTOR降低(如FGR、MNR、母亲吸烟)的并发症会降低出生体重，而mTOR增加(GDM、PCOS)则会增加新生儿体重。与不复杂妊娠的后代相比，后代在童年和成年时表现为肥胖或较高的体重指数，成年后表现为葡萄糖和胰岛素耐受性受损，胰腺β细胞质量和功能不足。明确胎儿对后代一生代谢健康的规划中的因果角色将有助于阻止肥胖和II型糖尿病的恶性循环。
Robust evidence of fetal programming of adult disease has surfaced in the last several decades. Human and preclinical investigations of intrauterine insults report perturbations in placental nutrient sensing by the mechanistic target of rapamycin (mTOR). This review focuses on pregnancy complications associated with placental mTOR regulation, such as fetal growth restriction (FGR), fetal overgrowth, gestational diabetes mellitus (GDM), polycystic ovarian syndrome (PCOS), maternal nutrient restriction (MNR), preeclampsia (PE), maternal smoking, and related effects on offspring birthweight. The link between mTOR-associated birthweight outcomes and offspring metabolic health trajectory with a focus on sexual dimorphism are discussed. Both human physiology and animal models are summarized to facilitate in depth understanding. GDM, PCOS and fetal overgrowth are associated with increased placental mTOR, whereas FGR, MNR and maternal smoking are linked to decreased placental mTOR activity. Generally, birth weight is reduced in complications with decreased mTOR (i.e., FGR, MNR, maternal smoking) and higher with increased mTOR (GDM, PCOS). Offspring display obesity or a higher body mass index in childhood and adulthood, impaired glucose and insulin tolerance in adulthood, and deficiencies in pancreatic beta-cell mass and function compared to offspring from uncomplicated pregnancies. Defining causal players in the fetal programming of offspring metabolic health across the lifespan will aid in stopping the vicious cycle of obesity and type II diabetes.
登录
查看更多内容
影响因子：
5.4
作者：
Bellone, S;Rapa, A;Bona, G
通讯作者：
Bona, G
影响因子：
3.1
作者：
Aiko Y;Askew DJ;Aramaki S;Myoga M;Tomonaga C;Hachisuga T;Suga R;Kawamoto T;Tsuji M;Shibata E
通讯作者：
Shibata E
影响因子：
8
作者：
Akhaphong, Brian;Baumann, Daniel C.;Alejandro, Emilyn U.
通讯作者：
Alejandro, Emilyn U.
DOI：
10.1017/s2040174415001154
发表时间：
2015-08-01
影响因子：
1.7
作者：
Fahlbusch, F. B.;Hartner, A.;Rascher, W.
通讯作者：
Rascher, W.
影响因子：
7.2
作者：
Doherty, Dorota A.;Newnham, John P.;Hart, Roger
通讯作者：
Hart, Roger