Effects of a histone methyltransferase inhibitor on fertility in an animal model of endometriosis

Endometriosis is an inflammatory, painful gynecologic disease with no cure and limited treatment options. Epigenetics, including histone modifications, play a key role in the etiology of endometriosis, therefore it has been hypothesized that epigenetic drugs can be used as a non‐hormonal therapeutic alternative for endometriosis. Following up on our observation that treatment with a histone methyltransferase inhibitor (HMTi) significantly decreased disease parameters such as size of vesicles in an animal model of endometriosis, this study was designed to investigate the effects of HMTi on fecundity correlates (e.g,. changesin expression of fertility‐associated genes and in ovarian and endometrial histology). Two weeks after endometriosis induction in female Sprague Dawley rats, we injected rats intraperitoneally with HMTi or vehicle for four weeks. At sacrifice, the ovaries and uterus of the rats treated with HMTi or vehicle were collected. mRNA was extracted from the right ovary for qPCR of fertility associated genes (ER, LH, CYP19) and secondary and antral follicles were counted in the left paraffin‐embedded ovary. The uterus was paraffin‐embedded to evaluate histopathological parameters. Treatment did not modify the expression of any of the genes studied, and did not significantly affect the number of ovarian follicles compared to vehicle. In addition, HMTi did not cause any histopathological changes in uteri compared to vehicle. These observations suggest that HTMi does not negatively influence fecundity in this model, a possibility that is currently being investigated in vivo. Support or Funding Information Special thanks to our funding from Puerto Rico Science, Technology & Research Trust, PHSU RISE (NIGMS Grant R25GM062406), PHSU Magic Core & Brain Core (NIMHD Grant MD007579), Puerto Rico Biobank (NCI Grant 1U54CA163071), PRISE Program from University of Puerto Rico, Ponce Campus (NIGMS Grant R25GM096955) and Porter Physiology Development Fellowship. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .