Optimal levels of nitric oxide are crucial for implantation in mice

Abstract

This study was performed to clarify the critical role of optimal levels of nitric oxide on fecun-dity in mice during the implantation period. Mature female pregnant mice were treated with either nitric oxide donor molsidomine (3, 15, 60 mg kg^-1) or nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-name; 0.3, 1.5, 6 mg kg^-1) every 12 h, seven times from the night of Day 2 to Day 5 of gestation. They were killed on Day 14 of gestation. Pregnancy rates in each group (n = 22) and the number of live or absorbed fetuses in each mouse was calculated. The pregnancy rates in the experimental group were reduced in a dose-dependent manner. The rate in the control group was 100%, whereas those in the 60-mg mol-sidomine and 6-mg L-name groups were 40.9 and 31.8%, respectively. Histological analysis of uteri on Day 5 of gestation after treatment with 60 mg molsidomine or 6 mg L-name suggested retarded decidualization of stromal cells or defective function of predecidualized cells. In conclusion, optimal levels of nitric oxide are crucial for endometrial function and embryo implantation.