Chorionic somatomammotropin impacts early fetal growth and placental gene expression.
Chorionic somatomammotropin impacts early fetal growth and placental gene expression.
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DOI：
10.1530/joe-18-0093
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发表时间：
2018-06
期刊：
影响因子：
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通讯作者：
Anthony RV
中科院分区：
文献类型：
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作者：
Jeckel KM;Boyarko AC;Bouma GJ;Winger QA;Anthony RV
几个发育窗口，包括胎盘，必须协商，以建立和维持妊娠。胎盘功能受损可导致先兆子痫和/或宫内生长受限（IUGR），导致婴儿死亡率和发病率增加。据推测，绒毛膜促生长激素（CSH）在胎儿发育中起着重要作用，可能通过改变母体和胎儿的代谢。最近，利用慢病毒介导的绵羊体内RNA干扰，我们证明了CSH缺乏导致近期（妊娠135天；dGA）胎儿和胎盘大小显著减少，胎儿肝脏基因表达改变。我们试图检测CSH缺乏对妊娠早期（50 dGA）胎儿和胎盘大小的影响，并检测50和135 dGA时胎盘基因表达。在50 dGA时，CSH缺乏妊娠的子宫静脉CSH浓度降低41% (P≤0.05)，胎体和肝脏重量显著（P≤0.05）降低（≈21%）。在50和135 dGA时收获的胎盘显示出IGF1和IGF2 mRNA浓度的降低，以及SLC2A1和SLC2A3 mRNA的降低。相比之下，系统A、系统L和系统y+氨基酸转运蛋白家族各成员的mRNA浓度没有显著影响。在妊娠前三分之一末观察到的IUGR表明，先前报道的近期IUGR在妊娠早期开始，部分原因可能是胎盘内促卵泡刺激素的旁分泌作用不足。这些结果为CSH在妊娠进展和结局中的重要性提供了进一步令人信服的证据。
Several developmental windows, including placentation, must be negotiated to establish and maintain pregnancy. Impaired placental function can lead to pre-eclampsia and/or intrauterine growth restriction (IUGR), resulting in increased infant mortality and morbidity. It has been hypothesized that chorionic somatomammotropin (CSH), plays a significant role in fetal development, potentially by modifying maternal and fetal metabolism. Recently, using lentiviral-mediated in vivo RNA interference in sheep, we demonstrated significant reductions in near-term (135 days of gestation; dGA) fetal and placental size, and altered fetal liver gene expression, resulting from CSH deficiency. We sought to examine the impact of CSH deficiency on fetal and placental size earlier in gestation (50 dGA), and to examine placental gene expression at 50 and 135 dGA. At 50 dGA, CSH-deficient pregnancies exhibited a 41% reduction (P≤0.05) in uterine vein concentrations of CSH, and significant (P≤0.05) reductions (≈21%) in both fetal body and liver weights. Placentae harvested at 50 and 135 dGA, exhibited reductions in IGF1 and IGF2 mRNA concentrations, along with reductions in SLC2A1 and SLC2A3 mRNA. By contrast, mRNA concentrations for various members of the System A, System L and System y+ amino acid transporter families were not significantly impacted. The IUGR observed at the end of the first-third of gestation, indicates that the near-term IUGR reported previously, began early in gestation, and may have in part resulted from deficits in the paracrine action of CSH within the placenta. These results provide further compelling evidence for the importance of CSH in the progression and outcome of pregnancy.