The steroid hormone vitamin D is historically recognized for its relevance to bone health and calcium homeostasis. Recent years have witnessed a shift in focus to non-skeletal benefits of vitamin D; in this latter context, an accruing body of literature attests to a relevance of vitamin D to reproductive physiology. This article reviews the existing data about the diverse and previously underappreciated roles for vitamin D in reproductive health. A large body of available literature suggests that vitamin D deficiency may be detrimental to reproductive biology. However, given that our appreciation of vitamin D's role in reproductive physiology is almost entirely shaped by 'associative' studies and that data based on prospective interventional trials are limited, these concepts remain predominantly conjectural. Exact mechanisms whereby vitamin D may participate in the regulation of reproductive physiology remain far from clear. This review underscores a need for appropriately designed intervention trials to address the existing knowledge gaps and to delineate the specific roles of vitamin D signaling in reproductive biology.

Blood vessel growth and regression in human endometrium are regulated throughout the menstrual cycle. We sought a direct role of ovarian steroids on human endometrial endothelial cell (HEEC) proliferation and vascularization. To investigate the HEEC angiogenicity of sex steroids, we developed a reliable method for the isolation of HEEC, which allowed us to investigate the angiogenic effects of sex steroids using immunohistochemistry, immunocytochemistry, Western blot, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt proliferation, and vascular tube formation analyses. We were able to obtain 95-99% pure HEEC with our isolation technique. HEEC expressed predominantly estrogen receptor beta, minimally expressed estrogen receptor alpha, and but did not express progesterone (P(4)) receptors A and B in vivo and in vitro. Estradiol (E(2); 10(-10)-10(-8) m) and P(4) (10(-12)-10(-8) m), alone or in combination, induced HEEC proliferation compared with control values after 48 h of treatment (P < 0.05). Furthermore, after 8 d of treatment, there were significantly more angiogenic patterns in E(2) (10(-8) m), P(4) (10(-10) m), and E(2) plus P(4) (10(-8) and 10(-10) m) treatment groups compared with the control group (angiogenic scores, 2.95 +/- 0.16, 3.26 +/- 0.16, 3.06 +/- 0.17, and 1.93 +/- 0.15, respectively; P < 0.01). In conclusion, our results suggest that there are direct effects of E(2) and P(4) on HEEC and provide a new understanding of the physiological role of sex steroids in the regulation of endometrial events such as angiogenesis.

No abstract

The elevation of the proinflammatory chemoattractant cytokine levels in ectopic and eutopic endometrium of endometriosis implies an inflammatory basis for this disease. The relationship between endothelial cells and leukocytes is likely to be important in the regulation of inflammatory mediators of endometriosis. The aim of this study was to describe the temporal and spatial expression of IL-8 in human endometrial endothelial cells (HEEC) in vivo and to compare the in vitro regulation of IL-8 expression by sex steroids in HEEC from women with or without endometriosis. Eutopic endometrial tissues and endometriosis implants were grouped according to menstrual cycle phase and examined by immunohistochemistry for IL-8 expression. Endothelial cells of endometriotic implants expressed higher IL-8 immunoreactivity compared with endothelial cells of eutopic endometrium from women with or without endometriosis (P < 0.02). For in vitro studies, HEEC were isolated from women with or without endometriosis and grown to preconfluence. The purity of cultured HEEC (90-95%) was confirmed by immunocytochemistry using endothelium-specific markers, CD31 and CD146. The effects of estradiol (5 x 10(-8) m), progesterone (10(-7) m), or both on IL-8 mRNA and protein levels were analyzed by RT-PCR and ELISA, respectively. Sex steroids reduced the expression of IL-8 mRNA and protein in HEEC from women without endometriosis. In contrast, both estradiol and progesterone stimulated IL-8 mRNA and protein expression in HEEC from women with endometriosis. We postulate that the stimulation of chemokine expression by sex steroids in HEEC of women with endometriosis may play a role in the inflammatory aspect of this disease.

No abstract