title: Cell-free DNA induced apoptosis of granulosa cells by oxidative stress.
abstract: BACKGROUND
  Cell-free DNA is a DNA fragment that is produced by cell apoptosis which can affect the micro-environment of cell apoptosis. The levels of Cell-free DNA have been associated with successful rate of in vitro fertilization-embryo transfer (IVF-ET) and embryonic development. Our aim is to determine the relationship between cell-free DNA and embryo quality. The mechanisms of cell-free DNA in granulose and the apoptosis will be determined also.
  
  
  METHODS
  The study enrolled patients who were undergone IVF for the first time and grouped the patients as pregnant (n=130) and non-pregnant (n=59). The relationship was determined by statistical analysis between the levels of cell-free DNA in the follicular fluid and clinical data of IVF patients. Flow cytometry was done to detect the rate of granulosa cell apoptosis and intracellular reactive oxygen species (ROS) level. Western blotting and fluorescent quantitative PCR detected the apoptosis-related gene expressions.
  
  
  RESULTS
  Clinical data statistics showed that cell-free DNA levels were positively correlated with granulosa cell apoptosis and negatively correlated with embryo quality and pregnancy rates. High levels of cell-free DNA lead to increased ROS in granulosa cells and activated caspase through Fas/FasL that induced apoptosis.
  
  
  CONCLUSIONS
  High levels of cell-free DNA triggers granulosa cell apoptosis and influences oocyte maturation embryo development and pregnancy rates in IVF treatments. Cell-free DNA can be as a secondary criteria and predictive marker for the quality control of IVF embryo.
authors.affiliation: Reproduction Center, The Third Affiliated Hospital of ZhengZhou University, Henan, China.
authors.forename: Yichun
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Reproduction Center, The Third Affiliated Hospital of ZhengZhou University, Henan, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Reproduction Center, The Third Affiliated Hospital of ZhengZhou University, Henan, China. Electronic address: wangxingling20131@163.com.
authors.forename: Xingling
authors.initials: X
authors.lastname: Wang
authors.affiliation: Reproduction Center, The Third Affiliated Hospital of ZhengZhou University, Henan, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Cai
authors.affiliation: Reproduction Center, The Third Affiliated Hospital of ZhengZhou University, Henan, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Jia
authors.affiliation: Reproduction Center, The Third Affiliated Hospital of ZhengZhou University, Henan, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhao
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D000073888:Cell-Free Nucleic Acids / Q000494:pharmacology*; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D011247:Pregnancy; D015398:Signal Transduction / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000073888:Cell-Free Nucleic Acids; D053222:Fas Ligand Protein; D019014:fas Receptor
keywords: Cell-free DNA; Embryo quality; Granulosa cells; In vitro fertilization-embryo transfer (IVF-ET); ROS