Hu L, Lytras A, Bock M E, Yuen C K, Dodd J G, Cattini P A
Department of Physiology, University of Manitoba, Winnipeg, Canada.
Mol Cell Endocrinol. 1999 Nov 25;157(1-2):131-42. doi: 10.1016/s0303-7207(99)00152-5.
Diabetes is a common complication encountered during pregnancy. Earlier studies indicated that diabetic placentas bear morphological alterations consistent with modified placental differentiation, including alterations in the villous cellular content, structure, and total surface. Limited data associating the diabetic status with the expression of terminal placental differentiation markers are available. The human growth hormone/chorionic somatomammotropin (hGH/CS) family consists of five genes, one of which (GH-N) is expressed efficiently in pituitary while the other four (CS-A, B, L, and hGH-V) are expressed in placenta and represent ultimate placental differentiation markers. We developed and applied a sensitive RT-PCR method coupled with diagnostic restriction digestion to determine the relative levels of the hGH/CS family in normal pregnancies and examine whether their mRNA expression pattern is altered in pregnancies complicated by diabetes. We show that relative hCS-L content changes during placental development. Specifically, normal term placentas express higher relative levels of hCS-L, lower relative hGH-V levels and a 70-fold lower hGH-V/CS-L mRNA ratio compared to early placentas. Also, many term placentas from diabetic pregnancies express lower relative levels of hCS-L mRNA and a much higher hGH-V/CS-L mRNA ratio compared to normal term placenta, resembling more an early placenta pattern of expression. Thus, our study suggests that the expression of terminal placental differentiation markers, such as the hGH/CS genes, is altered in term placentas from these diabetics reflecting either impaired placental differentiation or post-differentiation impairment of normal placental function.
糖尿病是孕期常见的并发症。早期研究表明,糖尿病患者的胎盘存在形态学改变,与胎盘分化改变一致,包括绒毛细胞含量、结构和总表面积的改变。关于糖尿病状态与胎盘终末分化标志物表达之间关联的数据有限。人类生长激素/绒毛膜生长催乳素(hGH/CS)家族由五个基因组成,其中一个基因(GH-N)在垂体中高效表达,而其他四个基因(CS-A、B、L和hGH-V)在胎盘中表达,代表胎盘终末分化标志物。我们开发并应用了一种敏感的RT-PCR方法结合诊断性限制性酶切来确定正常妊娠中hGH/CS家族的相对水平,并研究糖尿病合并妊娠时其mRNA表达模式是否改变。我们发现hCS-L的相对含量在胎盘发育过程中发生变化。具体而言,与早期胎盘相比,足月正常胎盘表达更高水平的hCS-L、更低水平的hGH-V以及低70倍的hGH-V/CS-L mRNA比值。此外,与足月正常胎盘相比,许多糖尿病妊娠的足月胎盘表达更低水平的hCS-L mRNA和更高的hGH-V/CS-L mRNA比值,更类似于早期胎盘的表达模式。因此,我们的研究表明,这些糖尿病患者足月胎盘的胎盘终末分化标志物如hGH/CS基因的表达发生改变,这反映了胎盘分化受损或正常胎盘功能的分化后受损。