Title: Understanding the role of mRNA editing enzyme subunit APOBEC3B deletion in the pathogenesis of Endometriosis
Endometriosis is a benign inflammatory disease of female reproductive system, defined by the presence of endometrial like tissue outside the endometrial cavity. Endometriosis characterized by severe pelvic pain, unusual bleeding and inability to conceive resulting in severe physical, mental, and economical stress. Endometriosis possess a big risk for infertility and presently treatment options are very limited and mostly symptom based. Identification of new molecular target and mapping out the genetic pathway of endometriotic pathogenesis is the need of the hour. In the present study, we performed whole exome sequencing of endometriosis samples and compared it with the normal tissue samples to identify specific genetic alterations and its associated pathway. Endometriotic genome had novel genetic mutations that were not present in the normal samples which were validated by both clinical and in vitro studies. The study results showed that germline heterozygous deletion of mRNA editing enzyme subunit APOBEC3B was identified in about 96% of endometriosis samples. The presence of germline deletion was confirmed with blood, endometrium and normal ovary samples obtained from same patient using PCR based deletion assay. Sanger sequencing and subsequent insilico analysis suggested the presence of hybrid protein as a byproduct of APOBEC3B deletion. Further evaluations show, APOBEC3A-B hybrid protein activates A1CF causing several changes in the endometriotic microenvironment. This alteration contributes to the pathogenesis and manifestation of the disease. The effect of APOBECEB deletion was proved by in vitro experiments in cell line model, that displayed endometriosis like characteristic features upon silencing the APOBEC3B gene. Therefore, the results of the present study identify and confirms the deleterious effects caused by APOBEC3B deletion in endometriosis. These results might provide a base for the identification of complete pathogenesis mechanism of endometriosis, thereby moving a step closer to the better diagnosis and treatment options.
Audience Take Away Notes :
- This presentation will help shed the light on Endometriosis, a gynecological disorder.
- The present study helped us to identify gene signatures specific to endometriosis and effect of these gene hits on the pathogenesis of endometriosis
- Identification of APOBEC3B deletion in endometriosis might help in paving the way for efficient diagnosis, follow up and management of the disease
- Furthermore, analysis of APOBEC3A-B hybrid protein and the effect of A1CF in endometriosis needs to be examined to evaluate the complete picture of endometriosis patheogensis