Stine Gry Kristensen1, Ajay Kumar2, Bhanu Kalra2, Susanne Elisabeth Pors1, Jane Alrø Bøtkjær1, Linn Salto Mamsen1, Lotte Berdiin Colmorn3, Jens Fedder4, Erik Ernst5, Lisa Ann Owens6, Kate Hardy6, Stephen Franks6, Claus Yding Andersen1,7. 1. Laboratory of Reproductive Biology, The Juliane Marie Centre for Women, Children and Reproduction, University Hospital of Copenhagen, Copenhagen, Denmark. 2. Ansh Laboratories LLC, Webster, Texas. 3. The Fertility Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 4. Centre of Andrology & Fertility Clinic, Odense University, Odense, Denmark. 5. Department of Gynecology and Obstetrics, Aarhus University Hospital, Skejby, Denmark. 6. Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, London, United Kingdom. 7. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Abstract
CONTEXT: Members of the TGF-β family have been implicated in aberrant follicle development in women with polycystic ovaries (PCO). OBJECTIVE: Are there quantitative differences in the concentrations of TGF-β family members in fluid from human small antral follicles (hSAFs) in women with or without PCO? DESIGN AND SETTING: Follicle fluids (FFs) were collected from 4- to 11-mm hSAFs obtained from women undergoing ovarian tissue cryopreservation for fertility preservation. PATIENTS: FFs from 16 women with PCO (FF = 93) and 33 women without PCO (FF = 92). MAIN OUTCOME MEASURES: Intrafollicular concentrations of growth differentiation factor-9 (GDF9); anti-Müllerian hormone (AMH); inhibin-A and inhibin-B; total inhibin; activin-A, activin-B, and activin-AB; follistatin; follistatin-like-3; estradiol; and testosterone. RESULTS: Activin-B concentrations were reported in hSAFs, and concentrations were 10 times higher than activin-A and activin-AB concentrations. Activin-B showed significant associations with other growth factors. Concentrations of inhibin-A and inhibin-B were significantly lower in FFs from women with PCO, especially in hSAFs <8 mm in diameter. AMH concentrations did not differ between the groups in hSAFs <8 mm; however, AMH remained high in hSAFs >8 mm in women with PCO but decreased in women without PCO. Estradiol was significantly lower in FFs from women with PCO and showed significant associations with AMH. Concentrations of GDF9 showed significantly higher concentrations in PCO FFs of follicles >6 mm. CONCLUSIONS: Altered concentrations of TGF-β family members in hSAFs from women with PCO highlight altered growth factor signaling as a potential mechanism for follicle growth arrest.
CONTEXT: Members of the TGF-β family have been implicated in aberrant follicle development in women with polycystic ovaries (PCO). OBJECTIVE: Are there quantitative differences in the concentrations of TGF-β family members in fluid from human small antral follicles (hSAFs) in women with or without PCO? DESIGN AND SETTING: Follicle fluids (FFs) were collected from 4- to 11-mm hSAFs obtained from women undergoing ovarian tissue cryopreservation for fertility preservation. PATIENTS: FFs from 16 women with PCO (FF = 93) and 33 women without PCO (FF = 92). MAIN OUTCOME MEASURES: Intrafollicular concentrations of growth differentiation factor-9 (GDF9); anti-Müllerian hormone (AMH); inhibin-A and inhibin-B; total inhibin; activin-A, activin-B, and activin-AB; follistatin; follistatin-like-3; estradiol; and testosterone. RESULTS: Activin-B concentrations were reported in hSAFs, and concentrations were 10 times higher than activin-A and activin-AB concentrations. Activin-B showed significant associations with other growth factors. Concentrations of inhibin-A and inhibin-B were significantly lower in FFs from women with PCO, especially in hSAFs <8 mm in diameter. AMH concentrations did not differ between the groups in hSAFs <8 mm; however, AMH remained high in hSAFs >8 mm in women with PCO but decreased in women without PCO. Estradiol was significantly lower in FFs from women with PCO and showed significant associations with AMH. Concentrations of GDF9 showed significantly higher concentrations in PCO FFs of follicles >6 mm. CONCLUSIONS: Altered concentrations of TGF-β family members in hSAFs from women with PCO highlight altered growth factor signaling as a potential mechanism for follicle growth arrest.
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