Reduced expressions of connexin 43 and VEGF in the first-trimester tissues from women with recurrent pregnancy loss.

Xiaoping He,Qinfang Chen

doi:10.1186/s12958-016-0179-4

Abstract

BackgroundApproximately 45–50 % of the recurrent pregnancy loss (RPL) remain(s) unexplained that challenges its clinical management. Formation and development of placenta as well as angiogenesis are critical for successful pregnancy. Vascular endothelial growth factor (VEGF) and connexin 43 (Cx43) play important roles in angiogenesis and placenta development and aberration of these have been linked to RPL. We aimed to investigate whether the expressions of VEGF and Cx43 were altered in the first-trimester tissues (chorionic villi and decidua) collected from women with RPL compared to those from healthy early pregnant women.MethodsFirst-trimester chorionic villi and decidua were collected from pregnant women diagnosed RPL who ended up with surgical intervention (n = 28) in comparison to those collected from women requesting surgical termination of their unwanted normal first-trimester pregnancies (n = 28). These two groups of women were matched in age and gestational weeks. Tissues were analyzed for the protein and messenger ribonucleic acid (mRNA) expressions of Cx43 and VEGF by immunohistochemistry, western blot, and quantitative reverse transcription polymerase chain reaction (qRT-PCR).ResultsThe expressions of both Cx43 and VEGF at the level of mRNA and protein in the villi and decidua from women with RPL were significantly decreased compared with those from women with normal early pregnancy.ConclusionsReduction of Cx43 and VEGF expressed in the first-trimester tissues might indicate their important roles involved in RPL and thus holds the potential to develop pharmaceutical therapies for treatment of RPL.Electronic supplementary materialThe online version of this article (doi:10.1186/s12958-016-0179-4) contains supplementary material, which is available to authorized users.

Highlights

45–50 % of the recurrent pregnancy loss (RPL) remain(s) unexplained that challenges its clinical management
Recurrent pregnancy loss (RPL) refers to two or more consecutive pregnancy losses before 20 weeks of gestation defined by the American Congress of Obstetricians and Gynecologists (ACOG) [1, 2], and three or more pregnancy losses defined by Royal College of Obstetricians and Gynaecologists (RCOG) [3]
Protein and messenger ribonucleic acid (mRNA) expressions of Vascular endothelial growth factor (VEGF) in RPL group versus control group Compared to the control group, the immunoreactivity of VEGF in either chorionic villi or decidua was dramatically reduced in RPL group than that in control group as revealed by immunostaining (Fig. 1a, b)

Summary

Introduction

45–50 % of the recurrent pregnancy loss (RPL) remain(s) unexplained that challenges its clinical management. Vascular endothelial growth factor (VEGF) and connexin 43 (Cx43) play important roles in angiogenesis and placenta development and aberration of these have been linked to RPL. Recurrent pregnancy loss occurs about in 1 out of 100 pregnancies [5], causing depression, anxiety, stress and lowered self-esteem in During embryonic development, vascular endothelial growth factor (VEGF), a signal cytokine that stimulates vasculogenesis and angiogenesis [9], functions to create new blood vessels [10–12]. These suggest that impairment of angiogenesis and embryo development in RPL may be related to VEGF dysregulation.

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