Investigation of the role of nitric oxide synthase 2 in pregnancy using mutant mice.
Nitric oxide (NO) has been implicated as a signalling molecule in many cellular processes. As nitric oxide synthase 2 (NOS-2) is the main isoform expressed in mouse decidua and metrial gland, mice with a targeted disruption of the gene encoding NOS-2 were used to determine the potential roles of this enzyme during pregnancy. Reproductive success and the morphology of implantation sites throughout pregnancy were compared in NOS-2 deficient (NOS-2-/-) and wild-type (WT) mice. Although there were no significant differences in the duration of gestation or birth weight, NOS-2-/- mice had significantly fewer viable embryos at mid-gestation and delivered smaller litters than did WT mice. Histological sections of uteroplacental units from WT and NOS-2-/- mice were compared to establish the mechanisms underlying the loss of fetuses. No morphological differences were observed on day 6 or day 8 of gestation, indicating that implantation and early development of implantation sites were unaffected by the absence of NOS-2. However, by mid-gestation, decidua of NOS-2-/- mice had reduced cellularity and their decidual arteries had abnormally thickened walls. These observations were quantified by morphometric measurements, which showed a significant reduction in decidual cellular area and a significant increase in the blood vessel wall:lumen ratio in NOS-2-/- mice. The increase in the thickness of the blood vessel walls was not due to abnormal cellular infiltration or to altered expression of alpha-actin in vascular smooth muscle. These results indicate that NOS-2 has a functional role in the maintenance of decidual cellular integrity and development of appropriate uterine vasculature, and may play a supportive role in promoting embryo survival.
Burnett
T G
TG
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160-7400, USA.
Tash
J S
JS
Hunt
J S
JS
D000199:Actins / Q000032:analysis; D000818:Animals; D001158:Arteries / Q000473:pathology; D003656:Decidua / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005313:Fetal Death; D005865:Gestational Age; D006651:Histocytochemistry / Q000379:methods; D015151:Immunoblotting / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D007371:Interferon-gamma / Q000032:analysis; D007633:Keratins / Q000032:analysis; D008098:Litter Size; D051379:Mice; D018345:Mice, Knockout; D009252:NADPH Dehydrogenase / Q000032:analysis; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis
D000199:Actins; D012333:RNA, Messenger; D009569:Nitric Oxide; D007633:Keratins; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D009252:NADPH Dehydrogenase