Everything you ever wanted to know about hCG

Abstract

s / Placenta 35 (2014) A1eA112 A4 hormones. The placenta, therefore, has an important role in integrating the various endocrine signals involved in regulating resource allocation to fetal growth. PL2.2. EVERYTHING YOU EVER WANTED TO KNOW ABOUT HCG Thierry Fournier a,b UMR-S 1139, INSERM, University of Paris Descartes, Paris, France; b PremUp Foundation, Paris, France Human chorionic gonadotrophin (hCG) is the first hormonal message from the placenta to themother. It is detectable inmaternal blood two days after implantation and behaves like a super agonist of LH stimulating progesterone secretion by the corpus luteum. hCG has also a role in quiescence of the myometrium and local immune tolerance. Specific to the primate superior, hCG is a complex glycoprotein composed of two glycosylated subunits. The a-subunit is identical to the pituitary gonadotrophin hormones (LH, FSH, TSH), contains two N-glycosylation sites, and is encoded by a single gene, whereas the b-subunits in each of the hormones are distinct and confer receptor and biological specificity. The hCG b-subunit contains two sites of N-glycosylation and 4 sites of O-glycosylation. It is encoded by a cluster of genes that have evolved by duplication from LHB. CGA and CGB expressions are controlled by transcription factors such as AP2 and SP1 that recognize specific response elements in their promoters. hCG expression is regulated by growth factors and cytokines such as EGF, TNFa, activators of the cAMP signalling pathways and by ligands of the nuclear receptor PPARg. In this talk we will stress the importance of hCG glycosylation state, which varies with the stage of pregnancy, its trophoblastic source of production and in the pathology (choriocarcinoma, foeto-placental trisomy 21), modifying its biological activity and clearance. It is well established that hCG is mainly secreted by the endocrine syncytiotrophoblast into the maternal serumwhere it peaks around 10WG. In addition, we have reported that invasive extravillous trophoblasts also secrete hCG, and like choriocarcinoma cells, hyperglycosylated forms of hCG (hCG-H). In addition to its endocrine role, hCG has autocrine and paracrine role. It promotes formation of the syncytiotrophoblast and angiogenesis through LHCG receptor and activation of cAMP and phospholipase C signalling. In contrast, hCG-H does not signal through LHCGR but stimulates trophoblast invasion and angiogenesis by interacting with the TGFs receptor 2. hCG is largely used in antenatal screening and hCG-H may present a good serum marker to screen pregnancy diseases from placental origin. In conclusion, hCG is the major pregnancy glycoprotein hormone, whose maternal concentration and glycan structure change all along pregnancy. Depending on its source of production, the different glycoforms of hCG display different biological activities and functions that are essential for pregnancy outcome. PL2.3. PROFILE OF PLACENTAL GENE EXPRESSION AND PREGNANCY OUTCOME Maris Laan University of Tartu, Tartu, Estonia Placenta is a mammalian pregnancy-specific temporary organ encoded by the fetal genome. Normal implantation process and placental function throughout pregnancy have critical contributions to guarantee the intrauterine development of the offspring and modulation of the maternal gestational metabolism. Also, the following temporal dynamics of placental transcriptional regulation across three trimesters of gestation is of high importance. Aberrant placental gene expression profile and its temporal dynamics may affect the normal pregnancy course. And vice versa, perturbed placental transcriptome may reflect a consequence of impaired implantation, placental development and function. There are numerous reports addressing expression levels of biological candidate genes in placenta in relation to pregnancy complications. Past 10 years have brought along an abundance of studies addressing differential expression of placental genes in pregnancy complications using microarray approach. These analyses have provided novel insights into placental biology and served as discovery studies to identify biomarkers in order to predict pregnancy complications. Next-generation sequencing approach enables to obtain the most detailed coverage of transcriptomes. In order to bring novel insights into the placental transcriptional landscape in normal gestation and study differential gene expression in complicated pregnancies we performed total RNA and small RNA sequencing in 40 samples from term placentas. Samples were selected from the REPROMETA sample collection (Tartu, Estonia) and represent normal pregnancies along with the most clearly defined cases of preeclampsia and gestational diabetes, as well as small (SGA) and large (LGA) for gestational age births. This dataset represents a high quality resource to detect differences in placental transcription over diverse pregnancy courses, to investigation of key molecular changes in placentas from complicated pregnancies and to suggest novel potential biomarkers for monitoring the risk to develop pregnancy complications. PL3.1. INTERCELLULAR COMMUNICATION BY EXOSOMES IN PLACENTA Michel Record INSERM UMR 1037 CRCT Toulouse-Oncopole, TOULOUSE,