Effects of a Histone Methyltransferase Inhibitor on Fertility on a Rat Model of Endometriosis

Diego Bacarin Garcia, Inevy Seguinot Tarafa, Idhaliz Flores
In: Journal of Health Disparities Research and Practice · 2018 · vol. 12(4) , pp. 33 · W2969046271
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Histone methyltransferase inhibitor treatment in a rat model of endometriosis increased the expression of key genes related to embryonic implantation and ovarian development, suggesting a positive effect on fertility.

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The paper studied whether a histone methyltransferase inhibitor (HMTi) could improve fertility in a rat model of endometriosis by examining fertility-related gene expression. Female Sprague Dawley rats had endometriosis induced, then received intraperitoneal HMTi treatment for four weeks starting two weeks after induction; at sacrifice, uterine tissues were analyzed by RT2 Profiler PCR array to assess mRNA levels of fertility genes. HMTi altered only 2 of 84 genes tested, while increasing expression of key genes associated with embryonic implantation and ovarian development, and the authors note that these observations require additional in vivo investigation. This paper is centrally about endometriosis — it evaluates how histone methyltransferase inhibition affects fertility gene expression in a rat endometriosis model.

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Abstract

Endometriosis is an estrogen-dependent, inflammatory disease that affects 5-10% of women of reproductive age. It is defined as the growth of functioning endometrium outside the uterus that results in severe pelvic pain and often infertility. Currently, endometriosis has no cure, and available treatments have limited efficacy and side effects. Epigenetics play a key role in the etiology of this disease, and we have previously shown that treatment with histone methyltransferase inhibitors (HMTi) in an animal model of endometriosis significantly decreases vesicle development, suggesting the potential use of epigenetic drugs for endometriosis. The objective of this study was to investigate the effects of HMTi on fertility by analyzing the effects of the drug on expression of fertility genes in this model. Endometriosis induction was performed in female Sprague Dawley rats. Two weeks after, rats were treated intraperitoneally with HMTi for four weeks. At sacrifice, uterine tissues were collected and mRNA extracted to study fertility gene expression using a real-time polymerase chain reaction (RT2 Profiler PCR Array). HMTi treatment modified the expression of a limited number of genes (2 out of 84), and increased the expression of key genes related to embryonic implantation and development of the ovary. These observations suggest that HTMi has a positive effect on fertility, a possibility that requires additional investigations in vivo.
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Keywords

Epigenetics, Endometriosis; Infertility; histone methylation; histone methyltransferase inhibitors Disciplines Medicine and Health Sciences

Abstract

Endometriosis is an estrogen-dependent, inflammatory disease that affects 5-10% of women of reproductive age. It is defined as the growth of functioning endometrium outside the uterus that results in severe pelvic pain and often infertility. Currently, endometriosis has no cure, and available treatments have limited efficacy and side effects. Epigenetics play a key role in the etiology of this disease, and we have previously shown that treatment with histone methyltransferase inhibitors (HMTi) in an animal model of endometriosis significantly decreases vesicle development, suggesting the potential use of epigenetic drugs for endometriosis. The objective of this study was to investigate the effects of HMTi on fertility by analyzing the effects of the drug on expression of fertility genes in this model. Endometriosis induction was performed in female Sprague Dawley rats. Two weeks after, rats were treated intraperitoneally with HMTi for four weeks. At sacrifice, uterine tissues were collected and mRNA extracted to study fertility gene expression using a real-time polymerase chain reaction (RT2 Profiler PCR Array). HMTi treatment modified the expression of a limited number of genes (2 out of 84), and increased the expression of key genes related to embryonic implantation and development of the ovary. These observations suggest that HTMi has a positive effect on fertility, a possibility that requires additional investigations in vivo. Recommended Citation Garcia, Diego; Seguinot Tarafa, Inevy; and Flores, PhD, Idhaliz (2018) "Effects of a Histone Methyltransferase Inhibitor on Fertility on a Rat Model of Endometriosis," Journal of Health Disparities Research and Practice: Vol. 12: Iss. 4, Article 33. Available at: https://oasis.library.unlv.edu/jhdrp/vol12/iss4/33

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