Implantation requires synchronisation between blastocyst development and the transformation of the endometrium into a receptive state. During this period the uterus undergoes ‘closure’ with a complete loss of uterine fluid resulting in sandwiching of the blastocyst between the opposing uterine walls, thus initiating contact between blastocyst and the endometrium. The mechanism underlying fluid loss is currently thought to be associated with changes in Na⁺ absorption. This may involve changes in the expression of epithelial sodium channel transporter (ENaC) and cystic fibrosis transmembrane regulator (CFTR) in the uterine glandular epithelium (Chan et al. 2002). This view is supported by in vitro observation of amiloride-sensitive fluid absorption in the uterine glands of progesterone-treated rats (Naftalin et al. 2002). The current study extends this result to fluid absorption in vivo.

These experiments were performed in ovariectomised Wistar rats treated with steroids to mimic events in early pregnancy. The rats were divided into three groups (n = 6 per group): a control group receiving vehicle injection only; 3 days of 0.2 mg oestradiol treatment; or 3 days 0.2 mg oestradiol treatment followed by 3 days 4 mg progesterone treatment. The rats were anaesthetised with intraperitoneal injection of 0.1 ml (80 mg kg^-1) ketamine and 0.15 ml (10 mg kg^-1) xylazine HCl. Fluid absorption rates from the uterine horns were monitored by weight changes between inflow and outflow of uterine luminal perfusate and the concurrent changes in the effluent concentration of non-absorbable fluorescein(F)-dextran (molecular mass 450 kDa). The rats were humanely killed by cervical dislocation. ENaC and CFTR distribution was studied in fixed tissues using specific fluorescent antibodies and confocal microscopy.

Progesterone treatment resulted in an increased rate of fluid absorption which was reversed by amiloride, as evidenced by net changes in perfusate volume and increases in F-dextran concentration. Oestradiol treatment resulted in a small net secretion. ENaC was predominantly distributed around the glandular lumen in the progesterone-treated rats, whilst being absent in the oestradiol-treated and control animals. CFTR, however, was predominantly distributed around the glands in oestradiol-treated and less in progesterone-treated and control animals.

These observations suggest that progesterone upregulates ENaC in the uterine glands resulting in increased sodium absorption from the luminal fluid which may contribute to uterine closure.