Increased cystic fibrosis transmembrane conductance regulators expression and decreased epithelial sodium channel alpha subunits expression in early abortion: findings from a mouse model and clinical cases of abortion.

Min Zhou,Ying Liu,Yong Song,Li Xiao,Licong Shen,Wei Huang,Jing Fu,Hong-Long (James) Ji

doi:10.1371/journal.pone.0099521

Abstract

The status of the maternal endometrium is vital in regulating humoral homeostasis and for ensuring embryo implantation. Cystic fibrosis transmembrane conductance regulators (CFTR) and epithelial sodium channel alpha subunits (ENaC-α) play an important role in female reproduction by maintaining humoral and cell homeostasis. However, it is not clear whether the expression levels of CFTR and ENaC-α in the decidual component during early pregnancy are related with early miscarriage. CBA×DBA/2 mouse mating has been widely accepted as a classical model of early miscarriage. The abortion rate associated with this mating was 33.33% in our study. The decidua of abortion-prone CBA female mice (DBA/2 mated) had higher CFTR mRNA and protein expression and lower ENaC-α mRNA and protein expression, compared to normal pregnant CBA mice (BLAB/C mated). Furthermore, increased CFTR expression and decreased ENaC-α expression were observed in the uterine tissue from women with early miscarriage, as compared to those with successful pregnancy. In conclusion, increased CFTR expression and decreased ENaC-α expression in the decidua of early abortion may relate with failure of early pregnancy.

Highlights

A common pathology of pregnancies is early abortion, and 75% of early abortions are associated with embryo implantation failure [1]
The interaction between CFTR and ENaC has been proposed as the major mechanism regulating fluid absorption and secretion in the endometrial epithelia [6]
It is considered that downregulated CFTR and upregulated ENaC in the endometrial epithelia of mice are required to achieve maximal fluid absorption necessary for successful implantation [8]

Summary

Introduction

A common pathology of pregnancies is early abortion, and 75% of early abortions are associated with embryo implantation failure [1]. Embryo survival within the maternal uterus is affected by many factors, among which humoral homeostasis in the uterine cavity plays an important role in maintaining cellular homeostasis, which affects embryo implantation, differentiation and viability [2]. A large number of identified and postulated molecular mediators are involved in homeostasis regulation in early pregnancy. Humoral homeostasis is maintained via regulation of osmotic gradients, which are largely established by the transport of ions across the epithelium. Various factors are involved in maintaining osmotic gradients; in particular, cystic fibrosis transmembrane conductance regulators (CFTRs) function in cAMP-activated Cl2 secretion channels [4] and epithelial sodium channels (ENaCs) mediate the electrogenic influx of Na+ across membranes [5]. After mating in mice, decreased CFTR expression and increased ENaC expression are responsible for maximal fluid absorption, which ensures immobilization of the blastocyst and successful implantation [8]

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