title: Improvement of ovarian response and oocyte quality of aged female by administration of bone morphogenetic protein-6 in a mouse model.
abstract: BACKGROUND
  Advancing female age remains a difficult problem in infertility treatment. Ovarian angiogenesis plays an important role in follicular development and the activation of ovarian angiogenesis has been emerged as a new strategy for the improvement of age-related decline of oocyte quality. BMP-6 affect gonadotropin signals in granulosa cells and it promotes normal fertility by enabling appropriate response to LH and normal oocyte quality. BMP-6 has a potential role in regulation of angiogenesis and regulates the expression of inhibitor of DNA-binding proteins (Ids). Ids involved in the control and timing of follicle selection and granulosa cells differentiation. Especially, Id-1 is well-characterized target of BMP-6 signaling. Therefore, this study investigated whether co-administration of BMP-6 during superovulation process improves ovarian response, oocyte quality and expression of Id-1 and vascular endothelial growth factor (VEGF) in the ovary of aged female using a mouse model.
  
  
  METHODS
  Aged C57BL/6 female mice (26-31 weeks old) were superovulated by injection with 0.1 mL of 5 IU equine chorionic gonadotropin (eCG) containing recombinant mouse BMP-6 at various doses (0, 0.01, 0.1, 1, and 10 ng), followed by injection with 5 IU human chorionic gonadotropin (hCG) 48 h later. Then, the mice were immediately paired with an individual male. The aged control group was superovulated without BMP-6. Young mice of 6-9 weeks old were superovulated without BMP-6 as a positive control for superovulation and in vitro culture of embryos. Eighteen hours after hCG injection, zygotes were retrieved and cultured for 4 days. Both ovaries of each mouse were provided in the examination of ovarian expression of Id-1 and VEGF by reverse transcriptase-polymerase chain reaction, western blot, and immunohistochemistry.
  
  
  RESULTS
  Administration of 0.1 ng BMP-6 significantly increased the number and blastocyst formation rate of oocytes ovulated and ovarian expression of Id-1 and VEGF compared to aged control mice. These increased levels were comparable to those of young control mice.
  
  
  CONCLUSIONS
  This result suggests that BMP-6 during ovulation induction plays an important role in improvement of oocyte quality and ovarian response of aged female, possibly by regulating of ovarian Id-1 and VEGF expression.
authors.affiliation: Department of Obstetrics and Gynecology, Medical Research Institute, Pusan National University School of Medicine, Busan, Korea.
authors.forename: Seung S
authors.initials: SS
authors.lastname: Park
authors.forename: Min J
authors.initials: MJ
authors.lastname: Park
authors.forename: Bo S
authors.initials: BS
authors.lastname: Joo
authors.forename: Jong K
authors.initials: JK
authors.lastname: Joo
authors.forename: Jung B
authors.initials: JB
authors.lastname: Son
authors.forename: Kyu S
authors.initials: KS
authors.lastname: Lee
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D055418:Bone Morphogenetic Protein 6 / Q000008:administration & dosage*; D002478:Cells, Cultured; D005260:Female; D007247:Infertility, Female / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051798:Inhibitor of Differentiation Protein 1 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009865:Oocytes / Q000187:drug effects* / Q000502:physiology; D010053:Ovary / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010062:Ovulation Induction / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D055418:Bone Morphogenetic Protein 6; D051798:Inhibitor of Differentiation Protein 1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse