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Uterine Artery Remodeling in Pseudopregnancy Is Comparable to That in Early Pregnancy¹

Departments of Obstetrics and Gynecology,³ Molecular Genetics,⁴ and Pharmacology and Toxicology,⁵ and from the Research Institutes GROW⁶ and CARIM,⁷ University Maastricht, 6202 AZ Maastricht, The Netherlands

ABSTRACT

During pregnancy, the lumenal diameter and wall mass of the uterine artery (UA) increase, most likely in response to the increased hemodynamic strain resulting from the chronically elevated uterine blood flow (UBF). In this remodeling process, the phenotype of vascular smooth-muscle cells (VSMC) is transiently altered to enable VSMC proliferation. These phenomena are already seen during early pregnancy, when the rise in UBF is still modest. This raises the question whether the newly instituted endocrine environment of pregnancy is involved in the onset of the pregnancy-related UA remodeling. We tested the hypothesis that the conceptus is not essential for the onset of UA remodeling of pregnancy. Six control and 18 pseudopregnant (Postcopulation Days 5, 11, and 17; n = 6 per subgroup) C57Bl/6 mice were killed and UAs were dissected and processed for either morphometric analysis or immunohistochemistry. The latter consisted of staining UA cross sections for the differentiation markers smooth muscle alpha-actin and smoothelin, and for the proliferation marker MKI67. We analyzed the UA changes in response to pseudopregnancy by ANOVA. Data are presented as mean ± SD. By Day 11 of pseudopregnancy, the UA lumen was 25% wider and the media cross-sectional area 71% larger than in control mice. These differences were accompanied by reduced smoothelin expression and increased proliferation of UA medial VSMC. All UA morphological differences had returned or were in the process of returning to baseline values by Day 17 of pseudopregnancy. The structural and cellular aspects of UA remodeling as seen at midpregnancy are also seen in pseudopregnancy. These results support the concept that the conceptus does not contribute to the initiation of UA remodeling. We suggest that ovarian hormones trigger the onset of UA remodeling.

arterial remodeling, conceptus, mice, pregnancy, pseudopregnancy, uterine artery, uterus

¹ Supported by Research Institute Growth & Development (GROW), University Maastricht.

² Correspondence: Louis L.H. Peeters, Department of Obstetrics and Gynecology, University Hospital Maastricht, azM, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. FAX: 31 43 387 4765; lpe{at}sgyn.azm.nl

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