Evaluation of protein expression of microchimeric Y-chromosome in ovarian endometriosis

Abstract

Introduction: Endometriosis is a benign chronic gynaecological disorder with the presence of endometrium-like tissue outside the uterus. It affects 10% of the reproductive age group of women. The symptoms include infertility 30 – 50%, and dysmenorrhea 40 – 60%. Thus, endometriosis is a global burden with a wide range of symptomatology and hence causes difficulty for women who suffer from the disease. But the pathogenesis of the disease is yet to be understood. The presence of fetal Y-chromosome microchimerism in endometriosis is first reported using the FISH (Fluorescence In-Situ Hybridization) technique. Later, with a similar technique, conflicting results have been reported. The detection probes used were Y-specific chromosomes Yp11.1 – q11.1-Alpha Satellite DNA and Yq12 Satellite III DNA. The genomic evidence of Y chromosome microchimerism is evaluated using microarray expression followed by RNA-seq and quantitative RT-PCR experiments of target inserts for selected targets for further validation. This study reported the presence of 21 non-coding, and 33 protein-coding genes present in the Male Specific region of Y-chromosome (MSY) in ovarian endometriosis. Genomic studies have been reported in the literature but protein expression from Y-chromosome genes in ovarian endometriosis has not been reported. So, we aimed to evaluate protein expressions of EIF1aY, NLGN4Y, and ZFY in the eutopic endometrium of ovarian endometriosis. Method: The 2 study groups are allotted; Group A (Control) and Group B (Endometriosis). The tissue samples collected were annotated, processed, and performed western blot for identification of EIF1aY, ZFY, and NLGN4Y gene expression. The blots were scanned and analyzed using Bio-Rad Pharos FX TM Plus Molecular Imager and NIH Image J software ( http://imagej.nih.gov/ij/ ) respectively. Result: There was a significant increase in the gene expression of EIF1aY in the endometriosis group when compared to the control group (p < 0.01). The Spearman correlation scores for NLGN4Y and ZFY are strongly associated (r = 0.617). Conclusion: The ectopic site promotes the niche and eutopic tissue has an error which enhances the histogenesis. It appears from the present study that proteins coded from Y-chromosome genes, namely EIF1aY, NLGN4Y and ZFY are involved in the pathogenesis of ovarian endometriosis, which could be a potential therapeutic target in future. To the best of our knowledge, this is the first report suggesting the involvement of Y-microchimerism at the protein level in endometriosis. Further studies with larger sample sizes and different stages and phenotypes of endometriosis may bring forth more conclusive knowledge in this regard that seems to promote the histogenesis of endometriosis at ectopic sites. Department of Physiology, AIIMS, New Delhi. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.