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Aberrant DNA methylation in the PAX2 promoter is associated with Müllerian duct anomalies

  • General Gynecology
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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.

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Acknowledgements

The study was supported by grant 1708085QH201 of Natural Science Foundation of Anhui Province. We are very grateful for the technical support provided by Genesky Biotechnologies Inc., Shanghai.

Author information

Author notes

  1. Chao Wang and Qiong Xing have contributed equally.

Authors and Affiliations

  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

    Chao Wang, Qiong Xing, Bing Song, Guanjian Li, Zuying Xu, Tianjuan Wang, Yujie Chen, Yuping Xu & Yunxia Cao

  2. NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China

    Chao Wang, Qiong Xing, Tianjuan Wang & Yunxia Cao

  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

    Chao Wang, Qiong Xing, Tianjuan Wang & Yunxia Cao

  4. Anhui Province Key Laboratory of Reproductive Health and Genetics, No. 81 Meishan Road, Hefei, 230032, Anhui, China

    Bing Song, Guanjian Li, Zuying Xu, Yujie Chen & Yuping Xu

  5. Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China

    Bing Song, Guanjian Li, Zuying Xu, Yujie Chen & Yuping Xu

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  1. Chao Wang
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Contributions

CW: data collection, data analysis, manuscript writing; QX: sample collection, data collection, manuscript writing; BS: data collection; GL: data analysis, manuscript editing; ZX: sample collection; TW: data analysis, manuscript editing; YC: sample collection; YX: sample collection; YC: project development, manuscript editing.

Corresponding author

Correspondence to Yunxia Cao.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Wang, C., Xing, Q., Song, B. et al. Aberrant DNA methylation in the PAX2 promoter is associated with Müllerian duct anomalies. Arch Gynecol Obstet 301, 1455–1461 (2020). https://doi.org/10.1007/s00404-020-05539-w

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  • DOI: https://doi.org/10.1007/s00404-020-05539-w

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