Comparative expression of hCG β-genes in human trophoblast from early and late first-trimester placentas

Abstract

<jats:p>Human chorionic gonadotropin (hCG) displays a major role in pregnancy initiation and progression and is involved in trophoblast differentiation and fusion. However, the site and the type of dimeric hCG production during the first trimester of pregnancy is poorly known. At that time, trophoblastic plugs present in the uterine arteries disappear, allowing unrestricted flow of maternal blood to the intervillous space. The consequence is an important modification of the trophoblast environment, including a rise of oxygen levels from about 2.5% before 10 wk of amenorrhea (WA) to ∼8% after 12 WA. Two specific β-hCG proteins that differ from three amino acids have been described: type 1 (CGB7) and type 2 (CGB3, -5, and -8). Here, we demonstrated in situ and ex vivo on placental villi and in vitro in primary cultures of human cytotrophoblasts that type 1 and 2 β-hCG RNAs and proteins were expressed by trophoblasts and that these expressions were higher before blood enters in the intervillous space (8–9 vs. 12–14 WA). hCG was immunodetected in villous mononucleated cytotrophoblasts (VCT) and syncytiotrophoblast (ST) at 8–9 WA but only in ST at 12–14 WA. Furthermore, hCG secretion was fourfold higher in VCT cultures from 8–9 WA compared with 12–14 WA. Interestingly, VCT from 8–9 WA placentas were found to exhibit more fusion features. Taken together, we showed that type 1 and type 2 β-hCG are highly expressed by VCT in the early first trimester, contributing to the high levels of hCG found in maternal serum at this term.</jats:p>

A Noninvasive Molecular Clock for Fetal Development Predicts Gestational Age and Preterm Delivery

“…CGA and CGB are the two subunits of HCG, known to play a major role in pregnancy initiation and progression and are involved in trophoblast differentiation (20). The trend observed for these two genes was consistent with what is known from HCG levels during pregnancy (21). Free CGB and PAPPA are also used as biochemical markers for risk of Down syndrome in the first trimester (22).…”

The Early Pregnancy Human Placenta Shares Hypomethylation Patterns Characteristic of Solid Tumors

“…Moreover, we also observed that hypomethylated blocks distinguish villous cytotrophoblasts before and after they first come into contact with maternal blood (weeks 10-12), providing the first evidence of an isolated non-cancer cell type with large-scale hypomethylated blocks. Furthermore, the result indicates that our finding of hypomethylated blocks in the placenta is not an artifact of 11 cell-type confounding related to changes in cellular composition during pregnancy. It also suggests that many of the methylation differences between early and late pregnancy placenta are associated with changes in the cytotrophoblast microenvironment including exposure to components of maternal blood and higher oxygen tension.…”

“…The chorionic villus represents the structural and functional unit that projects from the fetal placenta to invade the maternal uterine lining. The villous core, made of fibroblasts, mesenchymal cells, Hofbauer cells and fetal-placental vessels, is covered by layers of villous cytotrophoblasts and syncytiotrophoblasts, which are in direct contact with maternal blood [11]. DNA methylation was measured on the 450k array and quantified using Beta values.…”

“…Since substantial environment and cell type composition changes in the placenta occur during the nine months of gestation, we next sought to more narrowly define the time period and cell types associated with the observed placental methylome changes. We hypothesized that significant changes may occur concurrently with the major physiological shifts that occur when maternal blood first comes into contact with the chorionic villi during the 10th to 12th weeks of pregnancy [11]. To investigate methylation changes that occur during this period, we looked for differences that arise between the early first trimester (8-10 WG, n = 9) and late first trimester (12-14 WG, n = 10) villous cytotrophoblast samples (Fig 1a; Table S1), isolated ex vivo from chorionic villi samples using sequential enzymatic digestions.…”

Glioma-associated Oncogene 2 Is Essential for Trophoblastic Fusion by Forming a Transcriptional Complex with Glial Cell Missing-a

“…gov/ij/) was used to quantify the immunoreactive bands, and the normalized antigen signals were calculated from target proteinderived and ␤-actin-derived signals. ␤hCG levels in serum-free culture supernatants of BeWo cells and CTBs were determined by Enzyme Immunometric Assay kit as described previously (21).…”