title: Enhanced uterine artery stiffness in aged pregnant relaxin mutant mice is reversed with exogenous relaxin treatment.
abstract: Pregnancy is associated with a progressive remodeling of the uterine artery. This adaptation is influenced by local and systemic pregnancy-dependent factors. We recently demonstrated that the peptide hormone relaxin mediates uterine artery remodeling in late pregnant rats. The objective of this study in relaxin gene knockout (Rln(-/-)) mice was to test the hypothesis that relaxin deficiency throughout pregnancy disrupts uterine artery remodeling, an effect that is exacerbated by aging and reversed with relaxin treatment. Passive mechanical wall properties and extracellular matrix components were measured using pressure myography, quantitative PCR, and zymography in uterine arteries from pregnant wild-type (Rln(+/+)) and Rln(-/-) mice aged 5 and 8 mo on Days 12.5 and 17.5 pregnancy. In a second study, 8-mo-old Rln(-/-) mice received either placebo or human recombinant relaxin subcutaneously for 5 days from Day 12.5 pregnancy. Relaxin deficiency in pregnancy did not alter uterine artery remodeling in young mice. However, remodeling was impaired in older pregnant Rln(-/-) mice, resulting in significantly stiffer uterine arteries. Uterine arteries of aged Rln(-/-) pregnant mice had increased expression of elastin, whereas several matrix metalloproteinases and cell adhesion molecules were decreased relative to Rln(+/+) mice. Fetal weight was also significantly reduced in Rln(-/-) mice in late pregnancy in both young and old dams, whereas placental weight was unchanged. Arterial stiffness and reduced fetal weight were reversed after relaxin treatment. In conclusion, relaxin deficiency compromises uterine artery remodeling in older pregnant females, increasing the risk of pregnancy complications such as hypertension and intrauterine growth restriction.
authors.affiliation: Department of Zoology, The University of Melbourne, Parkville, Victoria, Australia. jgooi@unimelb.edu.au;
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Gooi
authors.forename: Meghan L
authors.initials: ML
authors.lastname: Richardson
authors.forename: Maria
authors.initials: M
authors.lastname: Jelinic
authors.forename: Jane E
authors.initials: JE
authors.lastname: Girling
authors.forename: Mary E
authors.initials: ME
authors.lastname: Wlodek
authors.forename: Marianne
authors.initials: M
authors.lastname: Tare
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Parry
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002448:Cell Adhesion; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D047109:Fetal Development; D018093:Gelatinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D010929:Placentation; D011247:Pregnancy; D012065:Relaxin / Q000502:physiology*; D055988:Uterine Artery / Q000033:anatomy & histology / Q000502:physiology*; D059289:Vascular Stiffness
chemical_list: D016326:Extracellular Matrix Proteins; D012065:Relaxin; D018093:Gelatinases
keywords: collagen; extracellular matrix; matrix metalloproteinase; pregnancy; relaxin gene knockout; uterine artery