Aquaporin Water Channel Genes Are Differentially Expressed and Regulated by Ovarian Steroids during the Periimplantation Period in the Mouse

Abstract

The periimplantation period is marked by edematous changes in the uterus. In the mouse, increased uterine vascular permeability occurs in response to estrogen and certain vasoactive mediators, but the mechanisms that regulate fluid transport during implantation are not fully understood. Aquaporins (AQPs) are a family of membrane channel proteins that facilitate bulk water transport. To assess their role in implantation, we examined the expression of AQPs 0-9 in the mouse uterus on d 1-8 of pregnancy. Our results show distinct uterine expression patterns for AQP1, AQP4, and AQP5. AQP1 is localized to the inner circular myometrium throughout the periimplantation period. AQP4 is highly expressed in the luminal epithelium on d 1 of pregnancy but barely detectable at the time of implantation. AQP5 is expressed at low levels in the glandular epithelium during early pregnancy but is markedly increased on d 5. By immunohistochemistry, AQP5 is localized in the basolateral region of the uterine glands. Treatment of adult ovariectomized mice with replacement steroids demonstrates an estrogen-induced shift in AQP1 signals from the myometrium to the uterine stromal vasculature, suggesting a role in uterine fluid imbibition. In contrast, AQP5 is induced only in estrogen-treated, progesterone-primed uteri. We also observed expression of AQP8 in the inner-cell mass and AQP9 in the mural trophectoderm of the implanting blastocyst. Collectively, these results suggest that members of the AQP family are involved in embryo and uterine fluid homeostasis during implantation.

Redistribution of aquaporins 1 and 5 in the rat uterus is dependent on progesterone: a study with light and electron microscopy

“…Furthermore, the expression of AQP1 was found in the inner circular layer of myometrium in control and progesterone treated animals (Richard et al 2003). Another study found AQP1 protein within both layers of the myometrium in all treatment groups with a slight increase in oestradiol treated mice and a slight decrease in the progesterone treated group, when compared with the control group (Jablonski et al 2003).…”

“…Another study found AQP1 protein within both layers of the myometrium in all treatment groups with a slight increase in oestradiol treated mice and a slight decrease in the progesterone treated group, when compared with the control group (Jablonski et al 2003). Animals treated with oestradiol or progesterone followed by oestradiol showed a biphasic response with expression initially in the inner circular layer of myometrium and 24 hrs later, a shift of AQP1 mRNA expression to the uterine stromal endothelial cells (Richard et al 2003).…”

“…However, AQP2 was shown to be strongly regulated by oestrogen, with protein present in luminal and glandular epithelium as well as in the myometrium (Jablonski et al 2003). AQP4 mRNA was not found in ovariectomised mice treated with either oil, oestradiol, progesterone or a combination of progesterone followed by oestradiol (Jablonski et al 2003, Richard et al 2003. In uterine luminal epithelial cells AQP5 mRNA was up-regulated after exposure of ovariectomised mice to progesterone followed by a nidatory dose of oestradiol (Richard et al 2003), but was absent in the control or oestrogen treated mouse uterus (Jablonski et al 2003).…”

“…AQP2 was found to be absent from the pregnant mouse uterus (Richard et al 2003). However, AQP2 was shown to be strongly regulated by oestrogen, with protein present in luminal and glandular epithelium as well as in the myometrium (Jablonski et al 2003).…”

Ion currents in embryo development

“…The role of aquaporins (AQPs), water channel proteins involved in regulation of cellular water homeostasis, was studied in sea urchin, mouse, and human embryos, demonstrating their expression and implication in mammalian preimplantation embryo development (Edashige et al, 2000;Amaroli et al, 2013;Nong et al, 2013;Xiong et al, 2013). Members of the AQPs family take part in the processes of blastocyst formation as physiological mediators of fluid movement across the trophectoderm during cavitation and implantation (Cho et al, 2003;Richard et al, 2003;Watson et al, 2004). The activation of the epithelial Na 1 channel (ENaC) in mouse endometrial epithelial cells by an embryoreleased serine protease, trypsin, triggers Ca 21 influx leading to a complex pathway involving prostaglandin E 2 release.…”