Smoking impairs angiogenesis during maturation of human oocytes

Abstract

This study determines whether smoking influences ovarian vascularization which thus may impair follicular development. Prospective laboratory study of follicular fluids and granulosa cells from patients undergoing in vitro fertilization. University Hospital Aachen, Germany. Fifty smoking women and 50 nonsmoking women. Cultivation of human granulosa cells. Cultivation of human umbilical vein endothelial cells (HUVECs) with either granulosa cell-conditioned medium or follicular fluid. Determination of clinical parameters. Quantification of soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) and cotinine. Mean sVEGFR-1 concentration in follicular fluid of smokers was 499.6 pg/mL compared with 159.2 pg/mL in nonsmokers. Correspondingly, supernatant of HUVECs cultured with follicular fluid from smoking and nonsmoking women showed, respectively, 1,174.1 pg/mL versus 794.2 pg/mL sVEGFR-1. The HUVECs incubated with conditioned medium from smokers' granulosa cells at culturing days 5, 9, 13, and 17 secreted, respectively, 1,712.4, 1,560.6, 1,619.0, and 1,635.0 pg/mL sVEGFR-1, whereas nonsmokers showed, respectively, 1,147.6, 1,067.2, 1,135.9, and 1,206.3 pg/mL sVEGFR-1. Mean cotinine concentration in smoking women was 83.9 ng/mL and in nonsmoking was 2.8 ng/mL. In all four comparisons, differences between groups reached statistical significance. This study showed that smokers secrete significantly higher amounts of sVEGFR-1 than nonsmokers, which may result in decreased ovarian vascularization and reduced oocyte maturation.