Postpartum reversal of the pregnancy-induced uterine artery remodeling in young, aging, and eNOS-deficient mice.

Objectives: The progressive rise in uterine blood flow (UBF) during pregnancy is accompanied by outward hypertrophic remodeling of the uterine artery (UA). After birth, UBF falls in concert with the sudden decline in uterine metabolic demands. Arterial remodeling associated with the reversal of increased blood flow has been described in large arteries. It is unclear whether this situation applies to small-sized resistance arteries such as the UA. We investigated the pattern of UA remodeling postpartum in relation to age and endothelial nitric oxide synthase (eNOS) deficiency.

Methods: Uterine artery of 2 and 10 days postpartum young (age 12 weeks), aged (age 40 weeks), and eNOS-deficient (eNOS( -/-), age 12 weeks) mice were dissected and processed for either morphometric analysis (lumen, wall mass) or immunohistochemistry (cellular differentiation, proliferation, and apoptosis). We used data of previously studied control (nonpregnant) and late-pregnant (17 days gestation) mice as reference.

Results: By 2 days postpartum, morphometric and cellular characteristics of the UA did not differ from those of late-pregnant UA. By 10 days postpartum, the UA was wider with wall mass being decreased by approximately 30%. Cytological parameters indicated a stable smooth muscle media. Apoptosis was only present in UA of 2 and 10 days pregnant mice. In eNOS(- /-) and aged mice, changes were smaller or absent, respectively.

Conclusions: The outward hypertrophic response of the UA induced by pregnancy regresses gradually postpartum. We speculate that persisting UA widening facilitates UA remodeling in a next pregnancy thereby favoring placentation and with it, allowing for a higher birth weight as usually observed in a second mammalian pregnancy.