Smoking impairs angiogenesis during maturation of human oocytes.
OBJECTIVE
This study determines whether smoking influences ovarian vascularization which thus may impair follicular development.


METHODS
Prospective laboratory study of follicular fluids and granulosa cells from patients undergoing in vitro fertilization.


METHODS
University Hospital Aachen, Germany.


METHODS
Fifty smoking women and 50 nonsmoking women.


METHODS
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.


METHODS
Quantification of soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) and cotinine.


RESULTS
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.


CONCLUSIONS
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.
Motejlek
Karin
K
Clinic of Gynecologic Endocrinology and Reproductive Medicine, University Hospital Aachen, Aachen, Germany. kmotejlek@ukaachen.de
Palluch
Frederike
F
Neulen
Joseph
J
Grümmer
Ruth
R
D000328:Adult; D000375:Aging / Q000378:metabolism*; D002478:Cells, Cultured; D003367:Cotinine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D009865:Oocytes / Q000254:growth & development* / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
D040281:Vascular Endothelial Growth Factor Receptor-1; D003367:Cotinine