Jane Alrø Bøtkjær1, Janni Vikkelsø Jeppesen1, Marie Louise Wissing2, Søren Kløverpris3, Claus Oxvig3, J Ian Mason4, Tanni Borgbo1, Claus Yding Andersen5. 1. Laboratory of Reproductive Biology, Juliane Marie Center for Women, Children, and Reproduction, Copenhagen University Hospital, Copenhagen University, Copenhagen, Denmark. 2. Holbæk Fertility Clinic, Holbæk, Denmark. 3. Department of Molecular Biology and Genetics, University of Aarhus, Aarhus, Denmark. 4. MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom. 5. Laboratory of Reproductive Biology, Juliane Marie Center for Women, Children, and Reproduction, Copenhagen University Hospital, Copenhagen University, Copenhagen, Denmark. Electronic address: yding@rh.dk.
Abstract
OBJECTIVE: To evaluate follicular fluid (FF) levels of pregnancy-associated plasma protein A (PAPP-A) in relation to levels of intrafollicular hormones. Furthermore, immunostaining of human follicles of varying diameters was studied for PAPP-A, antimüllerian hormone (AMH), and aromatase, and the biological activity of PAPP-A in FF was evaluated. DESIGN: Laboratory investigation. SETTING: University hospital. PATIENT(S): A total of 43 women with a total of 80 samples were obtained from three different size-groups of antral follicles collected before and after the LH surge. INTERVENTION(S): ELISA measurement of steroids, PAPP-A, and AMH, immunohistochemistry of PAPP-A, AMH, and aromatase on follicles of different diameter, and proteolytic activity of PAPP-A toward insulin-like growth factor (IGF)-binding protein 4 (IGFBP-4). MAIN OUTCOME MEASURE(S): Association between FF levels of PAPP-A and measured ovarian hormones, PAPP-A activity in FF, localization of PAPP-A, AMH, and aromatase in antral follicles. RESULT(S): A highly significant association between FF levels of PAPP-A and all measured hormones were obtained with positive associations toward E2 and P, whereas AMH, T, and A showed strong negative associations. PAPP-A proteolytic activity toward IGFBP-4 was detected in human FF. PAPP-A immunostaining shifted from being primarily present in theca cells of small antral follicles to being expressed in granulosa cells (GCs) of preovulatory follicles. In contrast, AMH expression became reduced with increasing follicular diameter. Aromatase expression was highly specifically localized to GCs of preovulatory follicles. CONCLUSION(S): The results suggest that PAPP-A is specifically involved in the regulation of steroidogenesis in human antral follicles. Local regulation of IGF-II activity may represent a mechanism by which PAPP-A exerts this function and highlights the importance of IGF signaling during follicular development.
OBJECTIVE: To evaluate follicular fluid (FF) levels of pregnancy-associated plasma protein A (PAPP-A) in relation to levels of intrafollicular hormones. Furthermore, immunostaining of human follicles of varying diameters was studied for PAPP-A, antimüllerian hormone (AMH), and aromatase, and the biological activity of PAPP-A in FF was evaluated. DESIGN: Laboratory investigation. SETTING: University hospital. PATIENT(S): A total of 43 women with a total of 80 samples were obtained from three different size-groups of antral follicles collected before and after the LH surge. INTERVENTION(S): ELISA measurement of steroids, PAPP-A, and AMH, immunohistochemistry of PAPP-A, AMH, and aromatase on follicles of different diameter, and proteolytic activity of PAPP-A toward insulin-like growth factor (IGF)-binding protein 4 (IGFBP-4). MAIN OUTCOME MEASURE(S): Association between FF levels of PAPP-A and measured ovarian hormones, PAPP-A activity in FF, localization of PAPP-A, AMH, and aromatase in antral follicles. RESULT(S): A highly significant association between FF levels of PAPP-A and all measured hormones were obtained with positive associations toward E2 and P, whereas AMH, T, and A showed strong negative associations. PAPP-A proteolytic activity toward IGFBP-4 was detected in human FF. PAPP-A immunostaining shifted from being primarily present in theca cells of small antral follicles to being expressed in granulosa cells (GCs) of preovulatory follicles. In contrast, AMH expression became reduced with increasing follicular diameter. Aromatase expression was highly specifically localized to GCs of preovulatory follicles. CONCLUSION(S): The results suggest that PAPP-A is specifically involved in the regulation of steroidogenesis in human antral follicles. Local regulation of IGF-II activity may represent a mechanism by which PAPP-A exerts this function and highlights the importance of IGF signaling during follicular development.
Authors: Fernanda R C L Almeida; Natasja G J Costermans; Nicoline M Soede; Annelies Bunschoten; Jaap Keijer; Bas Kemp; Katja J Teerds Journal: PLoS One Date: 2018-07-31 Impact factor: 3.240
Authors: Stine G Kristensen; Linn S Mamsen; Janni V Jeppesen; Jane Alrø Bøtkjær; Susanne E Pors; Tanni Borgbo; Erik Ernst; Kirsten T Macklon; Claus Yding Andersen Journal: Front Endocrinol (Lausanne) Date: 2018-01-12 Impact factor: 5.555