The online version of this article (doi:10.1186/1477-7827-10-117) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
SSP: conception and design, acquisition or analysis of data, and manuscript drafting, made the conception, participated in the design of the study and performed the statistical analysis and manuscript drafting. MJP: conception, design and execution of study, acquisition of data, participated in the conception and design of the study and performed the execution of study and acquisition of data. BSJ: execution of study, analysis of data and manuscript drafting, performed the execution of study, analysis of data and manuscript drafting. JKJ: analysis and interpretation of data, participated in analysis and interpretation of data. JBS: analysis and critical discussion, participated in analysis and critical discussion. KSL: drafting the manuscript or revising it critically for important intellectual content, and final approval of the version to be published, participated in drafting the manuscript or revising it critically for important intellectual content, and final approval of the version to be published. All authors read and approved the final manuscript.
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.
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.
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.
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.
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- Improvement of ovarian response and oocyte quality of aged female by administration of bone morphogenetic protein-6 in a mouse model
Seung S Park
Min J Park
Bo S Joo
Jong K Joo
Jung B Son
Kyu S Lee
- BioMed Central
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