title: Increased GDF9 and BMP15 mRNA levels in cumulus granulosa cells correlate with oocyte maturation, fertilization, and embryo quality in humans.
abstract: BACKGROUND
  Oocyte secreted factors (OSFs), including growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), play an important role in the process of follicular development and oocyte maturation. Since OSFs are expressed in oocytes and cumulus granulosa cells, the aim of the present study was to explore whether the expression levels of GDF9 and BMP15 mRNAs in cumulus granulosa cells can be used as molecular markers for predicting oocyte developmental potential.
  
  
  METHODS
  Cumulus cells of 2426 cumulus-oocyte complexes were collected from 196 female patients who underwent intracytoplasmic sperm injection (ICSI) and were used for mRNA detection on the egg retrieval day. Pearson correlation analysis was used to analyze the correlation between OSF expression and general physiological parameters. Partial correlation analysis was used to analyze the correlation between OSF expression and oocyte developmental potential. Covariance analysis was used to compare OSF expression among different groups. Receiver operating characteristic curves were used to examine the diagnostic value of GDF9 and BMP15 mRNA for predicting pregnancy.
  
  
  RESULTS
  The expression levels of GDF9 and BMP15 mRNAs were significantly associated with age, body mass index (BMI), oocyte maturation, normal fertilization, and cleavage rate (P < 0.05). The expression levels of GDF9 and BMP15 mRNAs in the group with high-quality embryos were significantly higher than those in the group without high-quality embryos (P < 0.05). The expression levels of GDF9 and BMP15 mRNAs in the pregnancy group were significantly higher than those in the nonpregnancy group (P < 0.05). The cut-off value of GDF9 mRNA for predicting pregnancy was 4.82, with a sensitivity of 82% and a specificity of 64%. The cut-off value of BMP15 mRNA for predicting pregnancy was 2.60, with a sensitivity of 78% and a specificity of 52%.
  
  
  CONCLUSIONS
  The expression levels of GDF9 and BMP15 mRNAs were closely associated with oocyte maturation, fertilization, embryo quality, and pregnancy outcome; therefore, GDF9 and BMP15 mRNAs in cumulus granulosa cells may be considered as new molecular markers for predicting oocyte developmental potential.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Rui-Qi
authors.initials: RQ
authors.lastname: Li
authors.forename: Song-Bang
authors.initials: SB
authors.lastname: Ou
authors.forename: Ning-Feng
authors.initials: NF
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Ren
authors.affiliation: Reproductive Medicine Research Center, Sixth Affiliated Hospital of Sun Yat-Sen University, 17 Shou-gou-ling Road, Guangzhou 510655, China. weilinaly@126.com.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Wei
authors.forename: Qing-Xue
authors.initials: QX
authors.lastname: Zhang
authors.forename: Dong-Zi
authors.initials: DZ
authors.lastname: Yang
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D055430:Bone Morphogenetic Protein 15 / Q000235:genetics / Q000378:metabolism*; D002681:China / Q000453:epidemiology; D054885:Cumulus Cells / Q000166:cytology / Q000378:metabolism*; D004477:Ectogenesis; D046149:Embryo Culture Techniques; D005260:Female; D055429:Growth Differentiation Factor 9 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D059471:In Vitro Oocyte Maturation Techniques; D007248:Infertility, Male; D008297:Male; D009866:Oogenesis; D011247:Pregnancy; D018873:Pregnancy Rate; D012333:RNA, Messenger / Q000378:metabolism*; D012372:ROC Curve; D012189:Retrospective Studies; D020554:Sperm Injections, Intracytoplasmic; D018454:Spouses; D015854:Up-Regulation
chemical_list: C525901:BMP15 protein, human; D015415:Biomarkers; D055430:Bone Morphogenetic Protein 15; C525897:GDF9 protein, human; D055429:Growth Differentiation Factor 9; D012333:RNA, Messenger