A synergistic negative effect of gestational smoke-exposure and small litter size on rat placental efficiency, vascularisation and angiogenic factors mRNA expression.

Zhen-Yan Chen,Ying Yao,Christopher Torrens

doi:10.1371/journal.pone.0181348

Abstract

Smoking increases the risk of pregnancy complications such as spontaneous abortion and low birth weight (LBW). By cigarette smoke exposure (gestational day, GD3-17), normal-litter-size pregnancy with low birth weight (NP-LBW) and small-litter-size pregnancy with normal birth weight (SP-NBW) in rats were induced. The placental weight in SP-NBW was twice the weight of the normal in contrast with the smaller placenta in NP-LBW. Compared with the normal, placental efficiency (expressed as fetus-to-placenta weight ratio) and placental vascularisation were significantly decreased in smoke exposed placentas with more obvious decrease in SP-NBW. For NP-LBW, decreased placental vascularisation was due to decreased labyrinth vascularisation which was caused by both decreased number density and diameter of fetal capillary. For SP-NBW, decreased placental vascularisation was due to reduced proportion of labyrinth in placenta and decreased labyrinth vascularisation which was caused by decreased fetal capillary number density. Real time RT-PCR analysis showed a tendency for decreased placental mRNA level of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang1) and tyrosine kinase receptor-2 (Tie2) in NP-LBW(P<0.1), and the tendency became obvious in SP-NBW(P<0.05). A tendency for decreased placental mRNA level of fms-like tyrosine kinase-1(Flt1) and angiopoietin-2 (Ang2) was also observed in SP-LBW(P<0.1). Our data demonstrated the synergistic negative effect of gestational smoke-exposure and small litter size on placental efficiency, placental vascularisation and placental angiogenic growth factor mRNA expression in rat.

Highlights

Smoking during pregnancy is associated with adverse pregnancy outcomes including spontaneous pregnancy loss and low birth weight
Studies investigated the alterations of Vascular endothelial growth factor (VEGF)/VEGFR and Ang/tyrosine kinase receptor-2 (Tie2) expression on placenta from maternal smoking are seldom and limited to VEGF and VEGFR1 on the assumption that maternal smoking is associated with a decreased risk of preeclampsia through reduced soluble form of VEGFR-1 which acts as a negative regulator of VEGF [14]
Given no decreased birth weight in small litters, smoke-exposed pregnancy was subdivided into small-litter-size pregnancy with normal birth weight (SP-NBW) and normal-litter-size pregnancy with low birth weight (NP-LBW)

Summary

Introduction

Smoking during pregnancy is associated with adverse pregnancy outcomes including spontaneous pregnancy loss and low birth weight. It has been reported that smoke exposure during pregnancy increased the risk of miscarriage by nearly 11% and reduced birth weight by nearly 10.75% [1]. Findings on the effects of maternal smoking on the structure of human placental vasculature are inconsistent [2,3,4,5,6,7,8,9,10]. Vascular endothelial growth factor (VEGF) and its receptors, fms-like tyrosine kinase-1(Flt, named VEGFR-1) and fetal liver kinase-1 (Flk, named VEGFR-2) are essential for vasculogenesis. VEGF, Flt and Flk are essential for endothelial cell proliferation, migration and tube-like structure formation, while Ang promotes the association of endothelial cells with periendothelial cells to mature and stabilize newly formed blood vessels. Some study showed no changed VEGF and VEGF receptor 1 mRNA in human placenta of smoking mothers of first trimester [15,16], while increased placental VEGF mRNA [17] and protein [18] of smokers of first trimester, and decreased soluble VEGF receptor 1 [14] were reported

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