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Aging Blunts Remodeling of the Uterine Artery During Murine Pregnancy

Yvonne P. G. Essers, BS

Lieke H. J. Simkens, MS

Quirine G. A. Teunissen, MS

Louis L. H. Peeters, MD

Jo G. R. De Mey, PhD

Department of Obstetrics and Gynecology, Research Institute Growth and Development (GROW), and the Departments of Molecular Genetics, and Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht, The Netherlands

Guillaume J. J. M. van Eys, PhD

Department of Obstetrics and Gynecology, Research Institute Growth and Development (GROW), and the Departments of Molecular Genetics, and Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht, The Netherlands; g.vaneys{at}gen.unimaas.nl

Objective: The progressive increase in uterine blood flow (UBF) during pregnancy is accommodated by morphologic changes in the uterine artery (UA) in a process defined as arterial remodeling. This process is accompanied by changes in cytoskeletal architecture of the arterial smooth muscle cells (SMCs) and surrounding extracellular matrix (ECM). Aging reduces flow-induced arterial remodeling. We studied changes in the murine UA during pregnancy and on the effects of aging on the capacity of the UA to remodel in response to pregnancy.

Methods: We determined morphologic and cytologic changes in UA from nonpregnant and pregnant mice aged 12 weeks (young) and 40 weeks (old) and correlated them with their reproductive performance.

Results: In young mice, pregnancy induced an early increase in UA wall mass, which preceded lumen widening. These changes were not accompanied by altered densities of elastin and collagen in the ECM of the medial layer. Smooth muscle cell proliferation increased in midepregnancy and was paralleled by a transient decrease in smoothelin and smooth muscle -actin expression. In old mice, these pregnancy-dependent changes in the UA wall were either absent or markedly reduced. Although by day 11 of pregnancy litter size did not differ between both age groups, the number of viable pups in old mice by day 17 of pregnancy and at birth was 25% and 60% less than in young mice.

Conclusions: Outward hypertrophic remodeling of the UA during pregnancy in young mice is characterized by transient phenotypic modulation and proliferation of SMCs and alterations in the composition of the ECM. In contrast, in older mice, UA remodeling is markedly reduced and accompanied with a loss of viable fetuses near term pregnancy.

Key Words: Arterial remodeling • uterine artery • aging • pregnancy • mouse

Journal of the Society for Gynecologic Investigation, Vol. 11, No. 5, 304-310 (2004)
DOI: 10.1016/j.jsgi.2004.02.004


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