Pro-opiomelanocortin in human pregnancy: evolution of maternal plasma levels, concentrations in cord blood, amniotic fluid and at the feto-maternal interface

Abstract

Objective: The human placenta normally expresses the pro-opiomelanocortin (POMC) gene. The pattern and secretory kinetics of POMC and/or POMC-derived peptides by the placenta during gestation is still debated. We recently demonstrated that full length POMC was a normal product of the human placenta. The aim of our study was to establish its normal secretory kinetics and to explore its physiological relevance. Design: In a prospective, longitudinal study, thirty normal pregnant women had monthly measurements of plasma POMC. In a cross-sectional study of 128 healthy pregnant women, plasma POMC and human chorionic gonadotrophin (hCG) were concomitantly measured to assess their correlation. Finally, POMC levels were assessed in venous and arterial cord blood samples, in amniotic fluid and in retroplacental blood. Methods: Plasma POMC was measured by a specific IRMA in unextracted blood or biological fluid. Results: Plasma POMC became detectable by the 8th week of pregnancy and reached its maximum at around the 20th week, remaining stable thereafter. The relationship between POMC and gestation time (weeks) best fitted with a third degree polynomia curve. A significant negative correlation (P=0.01) was observed between plasma levels of POMC and hCG after adjustment for gestation time to take into account the dependence of both hormones on this parameter. POMC was not secreted into the fetal circulation at term, but was present in very high levels in amniotic fluid. The highest levels of POMC were present in the retroplacental blood where the values were 35 times higher than in maternal blood; by comparison, corticotrophin releasing hormone and ACTH values in this compartment were twice or equal to those in the maternal blood. Conclusion: Placental POMC secretion increases during the first half of pregnancy and reaches a plateau from the 20th week to delivery. The inverse correlation between POMC and hCG plasma levels, and very high POMC levels at the feto-maternal interface suggest a physiological role for this precursor during pregnancy.

The role of epigenetic changes in preeclampsia

“…Comparing pregnant women with nonpregnant group, serum level of ACTH and β‐endorphin are higher in pregnancy group . In the first trimester of pregnancy, POMC can be detected in serum but it vanishes within days after delivery . White et al demonstrated differential methylation in CpG sites of POMC , AGT , CALCA , and DDAH1 genes in PE group compared with normal group (Table ).…”

Preeclampsia/Eclampsia candidate genes show altered methylation in maternal leukocytes of preeclamptic women at the time of delivery

“…Interestingly, intact POMC is not usually measurable in blood; however, it can be found in pregnancy early in the first trimester, and it disappears within days after delivery. 34 There have not been specific studies of gene expression or protein levels in maternal leukocytes in the pregnant or preeclamptic state.…”

Proopiomelanocortin, a polypeptide precursor with multiple functions: from physiology to pathological conditions

“…POMC plasma levels are higher in multiple pregnancies, display no diurnal variation, are unaffected by glucocorticoid administration, and return to normal within 3 days after delivery, consistent with its placental origin (19,65). Its physiological function remains unknown.…”

“…Conversely, a positive correlation is observed with CRH. POMC is selectively concentrated at the feto -maternal interface, which raises the question of a potential role in materno -fetal exchanges (65).…”