Abstract

IntroductionPlacenta is a complex organ that plays a significant role in the maintenance of pregnancy health. It is a dynamic organ that undergoes dramatic changes in growth and development at different stages of gestation. In the first-trimester, the conceptus develops in a low oxygen environment that favors organogenesis in the embryo and cell proliferation and angiogenesis in the placenta; later in pregnancy, higher oxygen concentration is required to support the rapid growth of the fetus. This oxygen transition, which appears unique to the human placenta, must be finely tuned through successive rounds of protein signature alterations. This study compares placental proteome in normal first-trimester (FT) and term human placentas (TP).MethodsNormal human first-trimester and term placental samples were collected and differentially expressed proteins were identified using two-dimensional liquid chromatography-tandem mass spectrometry.ResultsDespite the overall similarities, 120 proteins were differently expressed in first and term placentas. Out of these, 72 were up-regulated and 48 were down-regulated in the first when compared with the full term placentas. Twenty out of 120 differently expressed proteins were sequenced, among them seven showed increased (GRP78, PDIA3, ENOA, ECH1, PRDX4, ERP29, ECHM), eleven decreased (TRFE, ALBU, K2C1, ACTG, CSH2, PRDX2, FABP5, HBG1, FABP4, K2C8, K1C9) expression in first-trimester compared to the full-term placentas and two proteins exclusively expressed in first-trimester placentas (MESD, MYDGF).ConclusionAccording to Reactome and PANTHER softwares, these proteins were mostly involved in response to chemical stimulus and stress, regulation of biological quality, programmed cell death, hemostatic and catabolic processes, protein folding, cellular oxidant detoxification, coagulation and retina homeostasis. Elucidation of alteration in protein signature during placental development would provide researchers with a better understanding of the critical biological processes of placentogenesis and delineate proteins involved in regulation of placental function during development.

Highlights

  • Placenta is a complex organ that plays a significant role in the maintenance of pregnancy health

  • Twenty out of 120 differently expressed proteins were sequenced, among them seven showed increased (GRP78, protein disulfide-isomerase A3 (PDIA3), ENOA, ECH1, PRDX4, Endoplasmic reticulum resident protein 29 (ERP29), Enoyl-CoA hydratase mitochondrial (ECHM)), eleven decreased (TRFE, Serum albumin (ALBU), K2C1, ACTG, chorionic somatomammotropin hormone 2 (CSH2), PRDX2, Fatty acid-binding protein (FABP5), Hemoglobin subunit gamma-1 (HBG1), Fatty acid-binding protein (FABP4), K2C8, K1C9) expression in first-trimester compared to the full-term placentas and two proteins exclusively expressed in first-trimester placentas (MESD, myeloid-derived growth factor (MYDGF))

  • Elucidation of alteration in protein signature during placental development would provide researchers with a better understanding of the critical biological processes of placentogenesis and delineate proteins involved in regulation of placental function during development

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Summary

Introduction

Placenta is a complex organ that plays a significant role in the maintenance of pregnancy health. In the first-trimester, the conceptus develops in a low oxygen environment that favors organogenesis in the embryo and cell proliferation and angiogenesis in the placenta; later in pregnancy, higher oxygen concentration is required to support the rapid growth of the fetus This oxygen transition, which appears unique to the human placenta, must be finely tuned through successive rounds of protein signature alterations. Comparative analysis of gene expression in the villous tissues of first and second trimester versus TP showed that early gestational-age placenta is characterized by higher expression of genes involved in cell proliferation and apoptosis. In this regard, increased Wnt pathways activity in 1st and 2nd trimester is consistent with proliferative activity and invasiveness of trophoblasts. Oxygen regulates cellular proteome and function through the hypoxia-inducible factor (HIF) [8, 9] which is responsible for the hypoxic induction of hundreds of genes related to angiogenesis trophoblast differentiation and invasion by binding to hypoxia response elements (HREs) in their promoters or enhancers [7, 8, 10]

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