Increases in serum nitrite and nitrate of a few-fold adversely affect the outcome of pregnancy in rats.
The objective of this study was to evaluate serum nitrite and nitrate (nitrite/nitrate) concentrations that affect adversely pregnancy outcome. Pregnant rats, from day 2 to day 8 of pregnancy, were daily given subcutaneously several doses (5, 10, and 30 mg/rat) of diethylenetriamine-nitric oxide (DETA/NO). Serum nitrite/nitrate concentrations were measured using an HPLC system. Serum nitrite/nitrate concentrations increased dose-dependently with DETA/NO. Effects of DETA/NO on pregnancy outcome were assessed on day 14 of pregnancy. In rats given 5 mg DETA/NO, there was a significant increase in serum nitrite/nitrate concentrations (49.2 vs 24.6 micromol/l, P<0.001), and both placental weight and fetal weight decreased compared to control rats. Macroscopic bleeding in placenta was frequently observed in rats given DETA/NO. We further studied effects of DETA/NO on cultured trophoblastic BeWo cells. DETA/NO added to the culture medium increased nitrite/nitrate concentrations in the medium in a dose-dependent manner. Nitrite/nitrate concentrations in the medium over four times the concentration of control decreased progesterone in the medium at 24 h after the application of DETA/NO. The hormonal secretion was not affected by DETA only. This study shows for the first time nitrite/nitrate concentrations affecting adversely pregnancy outcome and function of the trophoblastic cells.
Inoue
Tsuneo
T
Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Kaibara
Muneshige
M
Sakurai-Yamashita
Yasuko
Y
Kawano
Masahiro
M
Ishimaru
Tadayuki
T
Taniyama
Kohtaro
K
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000378:metabolism; D003470:Culture Media; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D006207:Half-Life; D006728:Hormones / Q000378:metabolism; D006801:Humans; D009566:Nitrates / Q000097:blood*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009573:Nitrites / Q000097:blood*; D010920:Placenta / Q000187:drug effects; D010929:Placentation; D011073:Polyamines / Q000494:pharmacology; D011247:Pregnancy; D011256:Pregnancy Outcome; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014327:Trophoblasts / Q000187:drug effects
D006063:Chorionic Gonadotropin; D003470:Culture Media; D006728:Hormones; D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; D011073:Polyamines; C005391:diethylenetriamine; D009569:Nitric Oxide; D011374:Progesterone