The role of nitric oxide in the process of implantation in rats.

Nitric oxide (NO) plays an important role in cell signalling in many physiological systems, including reproduction. During pregnancy, oestrogen modulates uterine NO generation, and NO may play an intermediary role in the oestrogen-mediated effects on the uterus. Since oestrogen is actively involved in inducing endometrial receptivity to support the process of implantation, the role of NO in the process of implantation in rats was investigated. N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase (NOS), was administered in utero with or without sodium nitroprusside (SNP), a generator of NO, on different days during the preimplantation phase of gestation. The status of gestation in respect of implantation failure, endometrial receptivity and embryo development were assessed. L-NAME was administered at various doses (2-5 mg per uterine horn) and on different days of pregnancy (days 2-6 of pregnancy) to optimize the pregnancy terminating dose (absence of implantation site on day 8 of pregnancy) and the effective day of treatment. L-NAME led to failure of implantation when administered at 2.5 mg per uterine horn on day 3 of pregnancy. The characteristic preimplantation permeability changes in the uterus were significantly attenuated and embryo growth was retarded. The L-NAME-mediated effects were significantly reversed when SNP (100 micrograms) was co-administered with L-NAME. These findings suggest a role for NO in the process of implantation. The possible mechanism by which inhibition of the NO-NOS system may interfere with implantation is discussed.