Pregnancy complications due to an idiopathic faulty rise in uterine blood flow include repeated pregnancy loss and reduced weight of babies born at high altitude. To test the hypothesis that impaired arteriogenesis of the uterine artery (UA) might be causal, we studied mice overexpressing erythropoietin (tg6) with hematocrit levels around 0.85 that usually abort at day 9.5 of pregnancy. Shear stress, a factor inducing arteriogenesis, calculated from measure-ments of cardiac output, blood volume and vessel radius was 5-times lower in tg6 compared with wild type (wt) littermates. Consequently, UA growth was reduced and less pups (1.63 ±2.20 vs. 8.10 ±0.74 in wt) of lower weight (1.29 ±0.07g vs. 1.62 ±0.12g in wt) were delivered in first pregnancies. Only in subsequent pregnancies tg6 delivered a near normal number of pups. Birth weights, however, remained reduced. Hematocrit reduction to 0.60–0.70 by splenectomy (site of extramedullary erythropoiesis in tg6) did not reduce plasma erythropoietin levels whereas calculated shear stress normalized resulting already in the first pregnancy in normal UA growth, a trend in normalization of shear stress regulated gene expression and delivery of pups similar in number and weight to wt. Poor arteriogenesis might be a previously unappreciated reason for human pregnancy complications.