The Hormonal Control of Uterine Luminal Fluid Secretion and Absorption

Abstract

The secretion of uterine luminal fluid initially provides a transport and support medium for spermatozoa and unimplanted embryos, while the absorption of uterine luminal fluid in early pregnancy results in the closure of the lumen and allows blastocysts to establish intimate contact with the uterine epithelium. We have established an in vivo perfusion technique of the lumen to study the hormonal control of the events in the peri-implantation period. Fluorescein-labelled dextran was included in the perfusion medium to monitor fluid movements and the concentrations of Na(+) and CI(-) ions in the effluent were monitored. Using an established regimen of steroid treatment of ovariectomized rats mimicking early pregnancy, oestradiol caused fluid secretion, while progesterone resulted in an amiloride-sensitive fluid absorption. Fluid absorption peaked at about the expected time of implantation. The effect of progesterone could be inhibited by treatment with a high dose of oestradiol, by the anti-progestin RU486, and by the presence of an intra-uterine contraceptive device. Studies of expression of Na(+) and CI(-) channels (ENaC, CFTR) indicated that these channels were subject to tissue-specific regulation within the uterus, but more work is required to determine their role and the factors controlling their abundance and localization in early pregnancy.

Ultrasound-Guided Intrauterine Labeling of Rat Fetuses

“…These results are not in agreement with previous reports of humans in which administration of dyes (such as Fluorescein, Methylene Blue, or Evans Blue) directly into the amniotic sac demonstrated discoloration of the fetal skin that can be detected up to 2 weeks after the injection is administered [36,37]. The discrepancy of these results might be due to different absorption rates inter species with a more rapid absorption of the dyes by the rodent uterus [38][39][40]. In fact, preliminary experiments in our lab of intra-amniotic injection of dyes at day 15 of gestation and then harvesting fetuses at different time points, have demonstrated that the fetal skin was stained right after injection (data not shown).…”

Molecular determinants of uterine receptivity

“…Uterine luminal closure fails to occur in mice missing FK506 binding protein-4 (FKBP52), a co-chaperone for full progesterone receptor (PR) function (Tranguch et al, 2005a). Recent evidence shows that cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial Na + channel (ENaC) are the major gatekeepers regulating uterine fluid secretion and reabsorption (Salleh et al, 2005). Activation of ENaC is required for prostaglandin synthesis and release, which has been proven to be critical for embryo implantation (Ruan et al, 2012).…”

ENaCs and ASICs as therapeutic targets

“…In the uterus, only ␣ENaC was detected, and expression varied with the estrus cycle and inversely to the expression of CFTR (74). Increased fluid absorption during periods when ENaC expression is increased may be required to facilitate blastocyst implantation (335,427). Postimplantation, uterine expression of ENaC gradually declines (74).…”