Advanced Maternal Age Impairs Uterine Artery Adaptations to Pregnancy in Rats

Abstract

Advanced maternal age (≥35 years) is associated with pregnancy complications. Aging impairs vascular reactivity and increases vascular stiffness. We hypothesized that uterine artery adaptations to pregnancy are impaired with advanced age. Uterine arteries of nonpregnant and pregnant (gestational day 20) young (4 months) and aged (9 months; ~35 years in humans) Sprague-Dawley rats were isolated. Functional (myogenic tone, n = 6–10/group) and mechanical (circumferential stress-strain, n = 10–24/group) properties were assessed using pressure myography and further assessment of elastin and collagen (histology, n = 4–6/group), and matrix metalloproteinase-2 (MMP-2, zymography, n = 6/group). Aged dams had worse pregnancy outcomes, including smaller litters and fetal weights (both p 100 mmHg) cause forced vasodilation. Across the whole pressure range (4–160 mmHg), myogenic behavior was enhanced in aged vs. young pregnant dams (p = 0.0010). Circumferential stress and strain increased with pregnancy in young and aged dams (p p p < 0.05). In aged rats only, pregnancy increased MMP-2 active capacity. Altered functional and structural vascular adaptations to pregnancy may impair fetal growth and development with advanced maternal age.

Keywords

• advanced maternal age
• uterine artery
• pregnancy
• myogenic response
• circumferential stress-strain
• arterial structure