Pregnancy Stimulation of DNA Synthesis and Uterine Blood Flow in the Guinea Pig

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Pregnancy stimulates DNA synthesis in uterine artery smooth muscle cells. Unknown is whether DNA synthesis increases in all layers of the vessel wall in uterine or nonuterine vessels, the distribution and time course of the proliferative response in relation to the rise in uterine blood flow, and the extent to which a pregnancy-induced rise in DNA synthesis can be mimicked by chronic estradiol treatment. To measure DNA synthesis, we implanted bromodeoxyuridine (BrdU, 400 mg) s.c. for 14-d periods in three nonpregnant, nine pregnant, three vehicle, and five estradiol (2.5 mg/14 d)-treated guinea pigs. Uterine blood flow was measured in four nonpregnant and 18 pregnant animals using radiolabeled microspheres. Pregnancy stimulated DNA synthesis in the adventitia, media, and intima of the uterine artery, radial artery (the vessels deriving from the main uterine artery and entering the uterine wall), and uterine vein but not in the aorta or mesenteric artery. Maximal uterine artery medial area and labeling indices in all layers of the uterine artery, uterine vein, and the radial artery adventitia were attained by mid-pregnancy (d 28-42 of the guinea pig's 63-day gestation), whereas DNA synthesis increased progressively until term in the radial artery media and intima. The greatest rise in uterine artery blood flow (y) occurred after peak proliferation in the uterine artery and in concert with radial artery medial and intimal proliferation (y = 1.99 x 10(0.023x) where x is day postconception). 17beta-Estradiol treatment for 14 d in ovariectomized guinea pigs increased DNA synthesis in the radial artery adventitia and tended (p = 0.08) to increase labeling indices in the media of all vessels examined but did not fully reproduce the effects of pregnancy. We concluded that pregnancy-related, possibly hormonal stimuli prompted growth in all layers of the uterine artery wall by mid-pregnancy and served to initiate a rise in uterine blood flow. The resultant increase in flow and shear stress likely stimulated DNA synthesis in the radial artery which helped sustain the rise in flow near term.