title: Cytidine deaminase Apobec3a induction in fallopian epithelium after exposure to follicular fluid.
abstract: Ovarian carcinomas that originate from fallopian epithelial cells are suggested to arise due to repeated exposure to ovulatory follicular fluid (FF). Mechanistic explanation(s) for how this occurs are unknown. Here, we sought to understand if FF exposure to fallopian epithelial cells could induce DNA damage and expression of a known family of DNA mutators, apolipoprotein B mRNA editing enzyme, catalytic polypeptide (APOBEC) cytidine deaminases.
  
  
  
  Follicular fluid and matched patient plasma samples were obtained from donors. Fallopian epithelial cells (FT33-TAg, FT189, FT190, and FT194) were cultured with FF or plasma for 24h, and cell proliferation and DNA damage were assessed. Effects of FF on Apobec gene expression were determined by qRT-PCR and western blot analyses. Fallopian epithelial cells were transfected with an APOBEC3A expression vector and DNA damage was assessed.
  
  
  
  Follicular fluid exposure increased epithelial cell proliferation as measured by three independent methods, and DNA damage accumulation as assessed using three independent measures. This effect was specific to FF, as matched patient plasma did not have the same effects. Increased expression of Apobec3a was observed in fallopian epithelial cells following exposure to 5 of 8 patient FF samples, and transient overexpression of APOBEC3A was sufficient to induce double strand DNA breaks.
  
  
  
  Follicular fluid can induce cell proliferation and DNA damage accumulation in cultured fallopian epithelial cells. Increased expression of APOBEC3A, a known DNA mutator, may explain the high incidence of DNA damage after FF exposure. The role of Apobec3a in ovulation-induced inflammation warrants further investigation.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, United States. Electronic address: pbrachova@kumc.edu.
authors.forename: Pavla
authors.initials: P
authors.lastname: Brachova
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States. Electronic address: nalvarez@kumc.edu.
authors.forename: Nehemiah S
authors.initials: NS
authors.lastname: Alvarez
authors.affiliation: Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, United States. Electronic address: brad-van-voorhis@uiowa.edu.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Van Voorhis
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, United States. Electronic address: lchristenson@kumc.edu.
authors.forename: Lane K
authors.initials: LK
authors.lastname: Christenson
mesh_terms: D000328:Adult; D049109:Cell Proliferation / Q000502:physiology; D003564:Cytidine Deaminase / Q000096:biosynthesis* / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000201:enzymology* / Q000473:pathology; D005187:Fallopian Tubes / Q000201:enzymology* / Q000473:pathology; D005260:Female; D015571:Follicular Fluid / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D055815:Young Adult
chemical_list: D011506:Proteins; D012333:RNA, Messenger; C121399:APOBEC3A protein, human; D003564:Cytidine Deaminase
keywords: Apobec; DNA damage; Fallopian tube; Follicular fluid; Ovarian cancer; Ovulation