Journal article
Cytidine deaminase Apobec3a induction in fallopian epithelium after exposure to follicular fluid
Gynecologic Oncology, Vol.145(3), pp.577-583
06/2017
DOI: 10.1016/j.ygyno.2017.02.017
PMCID: PMC5447478
PMID: 28215840
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. •Follicular fluid induces DNA damage accumulation in fallopian epithelial cells.•Follicular fluid induces Apobec3a mRNA and protein expression in fallopian cells.•APOBEC3A overexpression is sufficient to induce double strand DNA breaks.
Details
- Title: Subtitle
- Cytidine deaminase Apobec3a induction in fallopian epithelium after exposure to follicular fluid
- Creators
- Pavla Brachova - Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, United StatesNehemiah S Alvarez - Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United StatesBradley J Van Voorhis - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, United StatesLane K Christenson - Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, United States
- Resource Type
- Journal article
- Publication Details
- Gynecologic Oncology, Vol.145(3), pp.577-583
- DOI
- 10.1016/j.ygyno.2017.02.017
- PMID
- 28215840
- PMCID
- PMC5447478
- NLM abbreviation
- Gynecol Oncol
- ISSN
- 0090-8258
- eISSN
- 1095-6859
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000002, name: NIH, award: HD082484; DOI: 10.13039/100007859, name: University of Kansas, award: P30 CA168524
- Language
- English
- Date published
- 06/2017
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9983930397302771
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