title: Abnormal estrous cyclicity after disruption of endothelial and inducible nitric oxide synthase in mice.
abstract: The roles of nitric oxide (NO) and nitric oxide synthase (NOS) in reproduction were studied by examining the estrous cycle of wild-type (WT) mice, inducible NOS (iNOS)-, and endothelial NOS (eNOS)-knockout mice. We observed an average estrous cycle of 4.8 +/- 0.2 days in WT mice. While we observed no significant influence of iNOS deficiency on cycle length, eNOS-knockout females showed a significantly longer estrous cycle (6.6 +/- 0.6 days; p < 0.03) than WT females, due to an extension of diestrus (p < 0.03). There was no influence of iNOS deficiency on ovulation rate compared with that in WT females; however, eNOS-knockout mice showed a significant reduction (p < 0.05) in ovulatory efficiency relative to WT or iNOS-knockout females. In contrast to WT females, in which the highest level of estradiol (E2) was observed at 1500 h of proestrus, iNOS-knockout females reached a peak of E2 at 1830 h of proestrus. In eNOS-knockout females, the peak of E2 occurred at 1830 h, as in iNOS-knockout mice; however, E2 levels were 5-fold and 3-fold higher (p < 0.05) than levels observed in WT and iNOS-knockout females, respectively. There was no effect of genotype on the plasma LH concentrations at proestrus. On the first day of diestrus, eNOS-knockout females showed significantly higher plasma E2 and progesterone levels (p < 0.05) relative to WT and iNOS-knockout females. The dysfunction in cyclicity, ovulation rate, ovarian morphology, and steroidogenesis in eNOS-knockout female mice strongly supports the concept that eNOS/NO plays critical roles in ovulation and follicular development.
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: A
authors.initials: A
authors.lastname: Jablonka-Shariff
authors.forename: S
authors.initials: S
authors.lastname: Ravi
authors.forename: A N
authors.initials: AN
authors.lastname: Beltsos
authors.forename: L L
authors.initials: LL
authors.lastname: Murphy
authors.forename: L M
authors.initials: LM
authors.lastname: Olson
mesh_terms: D000818:Animals; D004031:Diestrus; D004958:Estradiol / Q000097:blood; D004971:Estrus / Q000502:physiology*; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009929:Organ Size; D006080:Ovarian Follicle / Q000502:physiology; D010053:Ovary / Q000033:anatomy & histology; D010060:Ovulation / Q000502:physiology; D011359:Proestrus
chemical_list: D004958:Estradiol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse