Nitric oxide (NO) formation is upregulated during pregnancy, but its role in fetal and perinatal development has not been clearly defined. Both constitutive (cNOS) and inducible (iNOS) isoforms contribute to NO production in the utero-placental unit. cNOS is normally responsible for NO synthesis under physiologic conditions, whereas iNOS expression is a hallmark of host defense mechanisms and autoimmune disorders. The purpose of this study was to determine if iNOS is expressed in the utero-placental unit and fetus.STUDY DESIGN: Timed pregnant rats were sacrificed on days 14, 16, 19 and 21 of gestation and days 1, 3 and 7 of life. Fetal heart, intestine, liver, lung, spleen and thymus and maternal colon, placenta and uterus were harvested. RNA was extracted using the guanidine thiocyanate extraction method and iNOS expression determined from total RNA using RT-PCR. Additionally, uterine and placental tissues were evaluated for iNOS expression by immunohistochemical techniques. RESULTS: At 14 and 16 days gestation, fetal tissue (total) was positive for iNOS. At 19 and 21 days gestation, when dissection allowed testing of individual organs, iNOS was present in fetal lung and heart, intestine, spleen and thymus, respectively but absent in fetal liver. Results were similar at 1, 3 and 7 days postnatal life. Placenta, uterus and maternal colon were positive for iNOS throughout gestation. Immunohistochemical techniques reveal that the placental sinusoids and uterine smooth muscle as predominant sites of iNOS expression.CONCLUSIONS: The inducible enzyme, iNOS, a cytotoxic-cytostatic agent of the immune system, is expressed in the fetal tissue from the second trimester through early post-natal life. We postulate that the fetus can afford to utilize iNOS as a source of NO because the likelihood of peroxynitrite formation is reduced because of its hypoxic environment. It appears that the expression of iNOS and increased NO release perse, are not synonymous with cell injury.