Postpartum reversal of the pregnancy-induced uterine artery remodeling in young, aging, and eNOS-deficient mice.
OBJECTIVE
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.
Department of Obstetrics and Gynecology, Research Institute Growth and Development (GROWTH), University of Maastricht, Maastricht, The Netherlands.
Olivier W H
OW
van der Heijden
Yvonne P G
YP
Essers
Erwin
E
Wijnands
Jo G R
JG
Mey
Louis L H
LL
Peeters
Guillaume J J M
GJ
van Eys
D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D049590:Postpartum Period / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D014599:Uterus / Q000098:blood supply* / Q000201:enzymology*
D052250:Nitric Oxide Synthase Type III