Nitric oxide inhibits development of embryos and implantation in mice.
The objectives of this study were to evaluate the effects of a nitric oxide (NO) donor on embryo development in vitro and on implantation of embryos in vivo in mice. Mouse embryos (2-cell) were incubated in media containing different concentrations of diethylenetriamine/NO (DETA/NO), a nitric oxide donor, and development was monitored daily for 4 days. Specificity of NO effects was assessed by using DETA without NO or 48 h preincubated DETA/NO. In in-vivo studies, mated mice were continuously infused, subcutaneously, with various concentrations of DETA/NO or DETA through mini-osmotic pumps (from day 1 of pregnancy), and implantations in the uterus were assessed on day 6. None of the embryos progressed beyond 4-cell stage when exposed to 0.1 or 1.0 mM DETA/NO compared with 94.5% of control embryos that developed beyond the morula stage by day 4. Embryo development was unaffected by lower (0.001 and 0.01 mM) concentrations of DETA/NO, 48 h preincubated DETA/NO, or DETA only. Infusion of DETA/NO to mice caused inhibition of embryo implantation in a dose-dependent manner. No implantation sites were observed in mice infused with a daily dose of 20 micromol DETA/NO rate, compared with an implantation rate of 81.8% in control or DETA-treated mice. This study demonstrates for the first time that higher concentrations of NO inhibit both embryo development in vitro and implantation in vivo in mice.
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston 77555-1062, USA.
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Barroso
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Osuamkpe
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M
Nagamani
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Yallampalli
D000818:Animals; D001755:Blastocyst / Q000187:drug effects; D003864:Depression, Chemical; D010064:Embryo Implantation / Q000187:drug effects*; D004624:Embryo Transfer; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005307:Fertilization in Vitro; D051379:Mice; D009569:Nitric Oxide / Q000633:toxicity*; D009924:Organ Culture Techniques; D011073:Polyamines / Q000494:pharmacology; D011247:Pregnancy
D011073:Polyamines; C005391:diethylenetriamine; D009569:Nitric Oxide