Zaher Merhi1, Mohamad Irani, Angela D Doswell, Jennifer Ambroggio. 1. Department of Obstetrics, Gynecology, and Reproductive Sciences (Z.M., A.D.D., J.A.), Division of Reproductive Endocrinology and Infertility, University of Vermont College of Medicine, Burlington, Vermont 05401; and Department of Obstetrics and Gynecology (M.I.), Maimonides Medical Center, Brooklyn, New York 11219.
Abstract
CONTEXT: The interaction of advanced glycation end-products (AGEs) with their cellular receptor (RAGE) is implicated in the pathogenesis of abnormal ovarian follicular growth. RAGE has a circulating secretory receptor form, soluble RAGE (sRAGE), which neutralizes the action of AGEs and might exert a protective role on the follicular environment. OBJECTIVE: The objective of the study was to investigate whether serum or follicular fluid (FF) sRAGE levels are associated with markers of ovarian reserve. DESIGN, SETTING, AND PARTICIPANTS: Serum anti-Mullerian hormone (AMH) and sRAGE protein levels were correlated in 31 reproductive-aged women. An additional 33 women who underwent oocyte retrieval for in vitro fertilization were enrolled. AMH and its receptor (AMHR-II) mRNA levels were quantified in cumulus granulosa cells and FF sRAGE and AMH protein levels were measured. MAIN OUTCOME MEASURES: Granulosa cell AMH and AMHR-II gene expression, serum and FF AMH and sRAGE protein concentration, and number of oocytes retrieved were measured. RESULTS: In the serum, sRAGE levels were negatively correlated with body mass index (BMI) (r = -0.5, P < .001) but not with age or serum AMH. The higher the FF sRAGE, the lower the number of international units of gonadotropin needed per cycle independent of age, BMI, or day 3 FSH level (r = -0.4, P = .04). After adjusting for age, BMI, day 3 FSH, and the total dose of gonadotropins, FF sRAGE predicted the number of oocytes retrieved (R(2) = 0.27, P = .045). FF sRAGE positively correlated with FF AMH levels (r = 0.5, P = .0085). RT-PCR results showed no correlation between the FF sRAGE and AMH or AMHR-II mRNA levels. CONCLUSION: These data support a relationship between FF sRAGE and measures of ovarian reserve. The pathological significance of the harmful inflammatory AGEs in follicular health clearly requires further investigation. Targeting AGEs might offer potential therapeutic options for the treatment of diminished ovarian response.
CONTEXT: The interaction of advanced glycation end-products (AGEs) with their cellular receptor (RAGE) is implicated in the pathogenesis of abnormal ovarian follicular growth. RAGE has a circulating secretory receptor form, soluble RAGE (sRAGE), which neutralizes the action of AGEs and might exert a protective role on the follicular environment. OBJECTIVE: The objective of the study was to investigate whether serum or follicular fluid (FF) sRAGE levels are associated with markers of ovarian reserve. DESIGN, SETTING, AND PARTICIPANTS: Serum anti-Mullerian hormone (AMH) and sRAGE protein levels were correlated in 31 reproductive-aged women. An additional 33 women who underwent oocyte retrieval for in vitro fertilization were enrolled. AMH and its receptor (AMHR-II) mRNA levels were quantified in cumulus granulosa cells and FF sRAGE and AMH protein levels were measured. MAIN OUTCOME MEASURES: Granulosa cell AMH and AMHR-II gene expression, serum and FF AMH and sRAGE protein concentration, and number of oocytes retrieved were measured. RESULTS: In the serum, sRAGE levels were negatively correlated with body mass index (BMI) (r = -0.5, P < .001) but not with age or serum AMH. The higher the FF sRAGE, the lower the number of international units of gonadotropin needed per cycle independent of age, BMI, or day 3 FSH level (r = -0.4, P = .04). After adjusting for age, BMI, day 3 FSH, and the total dose of gonadotropins, FF sRAGE predicted the number of oocytes retrieved (R(2) = 0.27, P = .045). FF sRAGE positively correlated with FF AMH levels (r = 0.5, P = .0085). RT-PCR results showed no correlation between the FF sRAGE and AMH or AMHR-II mRNA levels. CONCLUSION: These data support a relationship between FF sRAGE and measures of ovarian reserve. The pathological significance of the harmful inflammatory AGEs in follicular health clearly requires further investigation. Targeting AGEs might offer potential therapeutic options for the treatment of diminished ovarian response.
Authors: Ali Ovayolu; Özkan Özdamar; İsmet Gün; Cansev Y Arslanbuğa; Tayfun Kutlu; Gülden Tunalı; Ramazan Uluhan Journal: Int J Clin Exp Med Date: 2015-06-15