Molecular derangements underlying pathogenesis of endometriosis

Abstract

Endometriosis is an inflammatory illness of the female reproductive system that is dependent on estrogen and It is differentiated from other cyst by the existence of endometrium like tissue outside of the uterus Endometriosis is distinguished by intense pelvic pain irregular bleeding and infertility that leads to extreme physical emotional and financial stress The risk of infertility associated with endometriosis is high and the existing treatment options are primarily symptom based The current study aims to investigate the genetic network associated with endometriosis and identify a new molecular target In this study we did whole exome sequencing on endometriosis samples and compared them to normal tissue samples to uncover specific genetic modifications and their connected pathways Studies conducted in vitro and clinical settings have confirmed that the endometriotic genome contains distinctive genetic variations that are absent in normal samples The results of present study identified around 96 percent of endometriosis samples have germline heterozygous deletion of the mRNA editing cytidine deaminase enzyme subunit APOBEC3B Using a PCR based deletion assay the presence of germline deletion was confirmed in blood endometrium and normal ovarian samples collected from the same patient Sanger sequencing followed by in silico analysis revealed that the loss of APOBEC3B resulted in the formation of hybrid protein Further investigations revealed that A1CF is activated by the hybrid protein APOBEC3A B leading to various modifications to the endometriotic microenvironment This modification helps in the growth and progression of endometriosis The impact of APOBEC3B deletion was demonstrated through in vitro experiments using a cell line model When the APOBEC3B gene was silenced the endometrial cells displayed characteristics of endometriosis Thus the present studies findings uncover and validate the negative implications of APOBEC3B loss in endometriosis These findings may serve as a foundation for the comprehensive pa