Chao Wang1,2,3, Qiong Xing1,2,3, Bing Song1,4,5, Guanjian Li1,4,5, Zuying Xu1,4,5, Tianjuan Wang1,2,3, Yujie Chen1,4,5, Yuping Xu1,4,5, Yunxia Cao6,7,8. 1. Department of Obstetrics and Gynecology, Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022, Anhui, China. 2. NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China. 3. Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei, 230032, Anhui, China. 4. Anhui Province Key Laboratory of Reproductive Health and Genetics, No. 81 Meishan Road, Hefei, 230032, Anhui, China. 5. Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China. 6. Department of Obstetrics and Gynecology, Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022, Anhui, China. caoyunxia6@126.com. 7. NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China. caoyunxia6@126.com. 8. Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei, 230032, Anhui, China. caoyunxia6@126.com.
Abstract
PURPOSE: Abnormalities during Müllerian duct and female reproductive tract formation during embryonic development result in Müllerian duct anomalies (MDA). Previous studies have identified a role for mutations in related genes and DNA copy number variation (CNV). However, the correlation between gene methylation and MDA remains to be understood. METHODS: Endometrial tissues were collected from patients with septate (n = 23) or normal uterus (n = 28). We detected the methylation status of CpG sites and mRNA levels of nine candidate genes, including HOXA10, EMX2, TP63, ITGB3, PAX2, LHX1, GSC, WNT4, and H19, using MethyTarget and quantitative real-time polynucleotide chain reaction (qRT-PCR), respectively RESULTS: Compared with healthy controls, we detected three hypomethylated CpG sites (P < 0.05) and increased mRNA levels of PAX2 (P < 0.05) in individuals with MDA. HOXA10, EMX2, TP63, ITGB3, LHX1, and GSC had 1, 1, 2, 1, 5, and 2 differentially methylated CpG sites (P < 0.05), respectively, but there were no significant differences in their mRNA levels (P > 0.05). WNT4 and H19 did not show differences in methylation (P > 0.05) and mRNA levels (P > 0.05). CONCLUSIONS: Aberrant DNA methylation within the promoter of PAX2 may contribute to the development of MDA by regulating its gene expression. However, the methylation status of HOXA10, EMX2, TP63, ITGB3, LHX1, GSC, WNT4, and H19, may not contribute to the development of MDA.
PURPOSE: Abnormalities during Müllerian duct and female reproductive tract formation during embryonic development result in Müllerian duct anomalies (MDA). Previous studies have identified a role for mutations in related genes and DNA copy number variation (CNV). However, the correlation between gene methylation and MDA remains to be understood. METHODS: Endometrial tissues were collected from patients with septate (n = 23) or normal uterus (n = 28). We detected the methylation status of CpG sites and mRNA levels of nine candidate genes, including HOXA10, EMX2, TP63, ITGB3, PAX2, LHX1, GSC, WNT4, and H19, using MethyTarget and quantitative real-time polynucleotide chain reaction (qRT-PCR), respectively RESULTS: Compared with healthy controls, we detected three hypomethylated CpG sites (P < 0.05) and increased mRNA levels of PAX2 (P < 0.05) in individuals with MDA. HOXA10, EMX2, TP63, ITGB3, LHX1, and GSC had 1, 1, 2, 1, 5, and 2 differentially methylated CpG sites (P < 0.05), respectively, but there were no significant differences in their mRNA levels (P > 0.05). WNT4 and H19 did not show differences in methylation (P > 0.05) and mRNA levels (P > 0.05). CONCLUSIONS: Aberrant DNA methylation within the promoter of PAX2 may contribute to the development of MDA by regulating its gene expression. However, the methylation status of HOXA10, EMX2, TP63, ITGB3, LHX1, GSC, WNT4, and H19, may not contribute to the development of MDA.
Authors: Laura Santana Gonzalez; Ioanna A Rota; Mara Artibani; Matteo Morotti; Zhiyuan Hu; Nina Wietek; Abdulkhaliq Alsaadi; Ashwag Albukhari; Tatjana Sauka-Spengler; Ahmed A Ahmed Journal: Front Cell Dev Biol Date: 2021-03-08