Controlled ovarian hyperstimulation, used in reproductive technology, has been reported to compromise endometrial receptivity, however mechanisms underlying this remain unclear. A recently developed rat ovarian hyperstimulation (OH) model showed a distended uterus at the time of implantation indicating a possible role for fluid transport molecules.

At the time of implantation in the rat, fluid transport molecules aquaporin 5 (AQP5), and claudin-4 are upregulated. Claudin-4 upregulation blocks the paracellular pathway allowing controlled reabsorption of fluid via transcellular AQP5 channels which are increased in the apical plasma membrane of mesometrial luminal uterine epithelial cells (UECs).

This study aims to investigate changes in these fluid transport pathways at the time of implantation in OH compared to normal pregnancy in an attempt to explain changes in endometrial receptivity in controlled OH in humans.

Female pregnant rats with regular oestrous cycles were supraovulated with an IP injection of 20IU PMSG followed 24hrs later with 20IU HCG. Rats were then mated overnight. Uteri were collected for immunohistochemistry and western blotting during OH and normal pregnancy.

A statistically significant increase in AQP5 was seen in UECs in OH compared to normal pregnancy. In OH pregnancy at the time of implantation, an increase in apical staining was seen in UECs across the entire lumen, not just confimed to the mesometrial pole as in normal pregnancy. A lack of claudin-4 staining in uterine epithelial cells at the time of implantation in OH rats was demonstrated as well as a statistically significant decrease in claudin-4 protein at this time.

There is a dramatic alteration in the location and quantity of several fluid transport molecules at the time of implantation in UECs of OH rats compared to normal pregnancy. This alteration in fluid dynamics may begin to explain the documented changes in endometrial receptivity seen in controlled OH in rodents and humans.