NITRIC-OXIDE SYNTHASE REGULATION DURING EMBRYONIC IMPLANTATION

It has previously been demonstrated that uterine nitric oxide synthase (NOS) activity increases before embryonic implantation in rats. The a im of the present work was to investigate the regulation and the physi ological relevance of the nitric oxide (NO) system in ovoimplantation. The increase in NOS activity in early pregnancy was found to be indep endent of the presence of embryos in the uterus. Whereas the Ca2+-depe ndent isoform of NOS increased gradually in the preimplantation days, the Ca2+-independent isoform increased just at the beginning of implan tation (Day 5, 1800 hours); then the activity of both isoforms decline d. Oestradiol, whose concentration peaks before implantation, might be regulating NOS activity in the uterus, since treatment of rats with t amoxifen, a receptor antagonist, reduces the activity of both isoforms to preimplantation levels. Intraluminal injections of L-NAME (0.5 mg kg(-1)), a competitive inhibitor of NOS, reduced by 50% the number of implanted embryos; this suggests that the NO system plays a role durin g implantation. The data suggest that oestradiol might be a modulator of NOS activity during nidation and that NO production is necessary to achieve a successful embryo implantation.