Aquaporin-4 deficiency induces subfertility in female mice

ObjectiveTo investigate the effects of aquaporin-4 (AQP4) on female fertility.DesignProspective, randomized animal study.SettingMedical university.Animal(s)AQP4+/+ and AQP4−/− female mice.Intervention(s)Eight- to 10-week-old virgin female AQP4+/+ and AQP4−/− mice were subjected to a mating study. Superovulation was carried out on 4-week-old AQP4+/+ and AQP4−/− mice. The protocol consisted of a single intraperitoneal (IP) injection with 5 units of pregnant mare serum gonadotropin (PMSG) for 48 hours, followed by 5 units of human chorionic gonadotropin (hCG) for an additional 14 or 48 hours.Main Outcome Measure(s)Pregnancy success, oocyte count, morphological changes in ovaries and uteri, and alterations of estrous cycle.Result(s)AQP4-null mice displayed subfertility as evidenced by a lower rate of pregnancy and decreased litter size. Further studies revealed that in AQP4-null mice, there were fewer numbers of antral follicles and corpora lutea in the ovaries and that uteri presented as hyporeactive to gonadotropins. In addition, in AQP4-null mice, superovulation induced by hCG and PMSG yielded fewer numbers of antral follicles, atretic follicles, corpora lutea, and oocytes in ovaries, and uteri exhibited a decreased response to exogenous gonadotropins.Conclusion(s)AQP4 deficiency induces subfertility in female mice.