Endometrial arteriogenesis: vascular smooth muscle cell proliferation and differentiation during the menstrual cycle and changes associated with endometrial bleeding disorders.

The cyclical regrowth of the human endometrial vasculature every 28 days following menstruation provides an excellent opportunity for studying arteriogenesis in a human tissue. Despite this, very little has been published to date about temporal or spatial changes in endometrial arteriolar structure or function. Immunohistochemical studies using vascular smooth muscle cell (VSMC) differentiation markers have identified spatially organised differences in VSMC phenotype. However, these have not significantly increased our understanding of how or when arteriogenesis occurs. Endometrial VSMC proliferation continues at a steady rate throughout the cycle, increasing in the specialised spiral arterioles in the mid and late secretory phases. Although estrogen and progesterone play a dominant role in regulating endometrial growth and regression, their direct involvement in arteriogenesis is less clear. Estrogen and progesterone receptors have been reported in endometrial VSMC, although heterogeneity of expression occurs. The angiopoietin/Tie axis has been investigated in endometrium, although the results of 3 studies published to date are contradictory, making conclusions about a role in arteriogenesis problematic. Abnormalities of arteriogenesis may play a role in disorders such as menorrhagia and breakthrough bleeding in contraceptive and hormone replacement therapy users. There is evidence that VSMC proliferation is reduced in spiral arterioles of women with menorrhagia, along with reduced pulsatility index of the uterine artery as shown by Doppler ultrasound. In women taking progestin-only contraception, endometrial perivascular alpha smooth muscle actin is reduced in those who suffer from breakthrough bleeding compared to those that don't. Considerable work is still required to elucidate when in the cycle, where in the tissue, and what mechanisms regulate endometrial arteriogenesis. Copyright 2003 Wiley-Liss, Inc.