%0 Journal Article
%T Regulation of soluble vascular endothelial growth factor receptor (sFlt-1/sVEGFR-1) expression and release in endothelial cells by human follicular fluid and granulosa cells
%A Ruth Gruemmer
%A Karin Motejlek
%A Daniela Berghaus
%A Herbert A Weich
%A Joseph Neulen
%J Reproductive Biology and Endocrinology
%D 2005
%I BioMed Central
%R 10.1186/1477-7827-3-57
%X We analyzed the influence of human follicular fluid obtained from FSH-stimulated women as well as of human granulosa cell conditioned medium on sFlt-1 production in and release from human umbilical vein endothelial cells (HUVEC) in vitro. Soluble Flt-1 gene expression was determined by RT-PCR analysis, amount of sFlt-1-protein was quantified by Sandwich-ELISA.Human follicular fluid as well as granulosa cell-conditioned medium significantly inhibit the production of sFlt-1 by endothelial cells on a posttranscriptional level. Treatment of cultured granulosa cells with either hCG or FSH had not impact on the production of sFlt-1 inhibiting factors. We further present data suggesting that this as yet unknown sFlt-1 regulating factor secreted by granulosa cells is not heat-sensitive, not steroidal, and it is of low molecular mass (< 1000 Da).We provide strong support that follicular fluid and granulosa cells control VEGF availability by down regulation of the soluble antagonist sFlt-1 leading to an increase of free, bioactive VEGF for maximal induction of vessel growth in the ovary.Angiogenesis is a rare process in normal adult organs predominantly occurring during wound healing and tumor growth. However, under physiological conditions it plays an important role in the female reproductive tract with regard to follicular development, corpus luteum formation, and uterine endometrial proliferation during the menstrual cycle [1,2]. Here, the cyclic corpus luteum of the ovary is the organ with the strongest physiological angiogenesis [3,4]. Defects in ovarian angiogenesis may contribute to a variety of disorders including anovulation and infertility, pregnancy loss, ovarian hyperstimulation syndrome, and ovarian neoplasms [5-7].During follicular growth, angiogenesis is restricted to the theca cell layer. After ovulation, however, massive angiogenesis occurs and new blood vessels penetrate the basement membrane of the follicle invading the growing corpus luteum [8]. The establ
%U http://www.rbej.com/content/3/1/57