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.
Barroso
R P
RP
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston 77555-1062, USA.
Osuamkpe
C
C
Nagamani
M
M
Yallampalli
C
C
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