Assessment of TET1 gene expression, DNA methylation and H3K27me3 level of its promoter region in eutopic endometrium of women with endometriosis and infertility

• Published in: Biomedicine & pharmacotherapy Vol. 150; p. 112989
• Main Authors: Adamczyk, Magdalena, Rawłuszko-Wieczorek, Agnieszka Anna, Wirstlein, Przemysław, Nowicki, Michał, Jagodziński, Paweł Piotr, Wender-Ozegowska, Ewa, Kedzia, Malgorzata
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.06.2022; Elsevier
• Subjects: DNA methylation; DNA Methylation - genetics; Endometriosis; Endometriosis - genetics; Endometriosis - metabolism; Endometrium - metabolism; Eutopic endometrium; Female; Gene Expression; H3K27me3; Histones - genetics; Histones - metabolism; Humans; Infertility; Infertility, Female - genetics; Mixed Function Oxygenases - genetics; Mixed Function Oxygenases - metabolism; Promoter Regions, Genetic - genetics; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; TET protein; HRM; TET; COX-2; PTGiP; RPLP0; r-ASRM; mRNA; PARP; ChIP; ACTB; FW; IWE; DNA methylation; cDNA; qPCR; CpG; PGE2; TET protein; HMGA2; Endometriosis; 5mC; MYT1; IW; HOX; Eutopic endometrium; PRC2; DNA; Infertility; IVF; EZH2; H3K27me3
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.112989

Endometriosis is the cause of infertility. The eutopic endometrium of women with endometriosis showed an aberrant expression pattern of multitude genes. The role of TET1 protein in the pathogenesis of endometriosis and related infertility is not sufficiently known. Further, knowledge on TET1 transcriptional control still remains incomplete. The aim of the study was assessment of TET1 gene expression, DNA methylation and H3K27me3 level of its promoter region in eutopic endometrium of women with endometriosis and infertility. The study included 44 infertile patients with endometriosis (IWE) and 77 infertile (IW) and fertile (FW) patients without endometriosis. The research material was eutopic endometrium. The TET1 mRNA level was analyzed by qPCR. Western blot was used to evaluate the level of TET1 protein. The level of DNA methylation and H3K27me3 level of TET1 gene’s promoter region were assessed using HRM and ChIP qPCR, respectively. The level of TET1 expression (TET1 mRNA; TET1 protein level) was lower in IWE during the implantation window (p < 0.001; p = 0.0329). The level of TET1 DNA methylation was higher in the secretory endometrium in mild and advanced IWE (p < 0.004; p < 0.008). H3K27me3 level did not differ between the study groups. The diminished expression of TET1 gene during the secretory phase, may account for the aberrant process of embryonic implantation in infertile endometriosis patients. DNA hypermethylation of TET1 gene is a potential relevant regulator of its expression. H3K27me3 occupancy does not affect the expression of TET1 gene in our study group. [Display omitted] •Impaired TET1 expression in the eutopic endometrium may result in ovulation failure.•Decreased expression of TET1 may cause infertility in women with endometriosis.•DNA hypermethylation of TET1 gene is a potential relevant regulator of its expression.•H3K27me3 occupancy in the regulation of TET1 expression is uncertain.