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Hypomethylation of CTGF Promoter in Placenta and Peripheral Blood of Pre-eclampsia Women

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Abstract

Pre-eclampsia (PE) is a serious pregnancy complication defined as hypertension combined with proteinuria. Previous report has indicated that the expression of connective tissue growth factor (CTGF) is upregulated in PE placentas. In this study, we aim to investigate the potential association between the methylation of the CTGF promoter and PE. The methylation status of CTGF promoter was assessed by methylation-specific PCR and the expression of CTGF was analyzed by real-time quantitative PCR and immunohistochemistry staining, in placental samples from PE patients and normal pregnant women. The methylation level of the CTGF promoter was also analyzed in peripheral blood DNA samples from 90 PE patients and 94 normal pregnant women and further confirmed by methylation-sensitive restriction enzyme digestion combined with real-time PCR. We found a decreased methylation rate of CTGF promoter in PE placentas compared with normal control. In addition, the frequency of hemimethylated (UM) promoter of CTGF in peripheral blood was significantly lower in the PE group (P = 0.019), while the frequency of overall methylated (MU + MM) promoter of CTGF in peripheral blood was lower (borderline significance P = 0.043) in the PE group. The percentage of methylated CpG in CTGF promoter was 30% lower in maternal blood of PE subjects than in controls. Moreover, the lower methylation frequency of CTGF promoter was in accordance with the higher expression of CTGF in trophoblast cells. Together, our data suggested an association between PE and the hypomethylation of CTGF promoter both in placentas and peripheral blood from a Chinese Han population.

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Abbreviations

PE:

Pre-eclampsia

CTGF:

Connective tissue growth factor

BP:

Blood pressure

PCR:

Polymerase chain reaction

MSP:

Methylation-specific PCR

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Funding

This work was supported by funding from the National Natural Science Foundation of China [No. 81600211], the Natural Science Foundation of Shandong Province [ZR2014HP017], and the Application and Basic Research Project of Qingdao [18-2-2-27-jch].

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Author notes

  1. Lu Zhang and Fei Zhao contributed equally to this work.

Authors and Affiliations

  1. Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China

    Lu Zhang, Qian Tang, Ru Zhang & Shiguo Liu

  2. Gynecology and Obstetrics Department, The Affiliated Hospital of Qingdao University, Qingdao, China

    Fei Zhao & Aiping Chen

  3. Department of Biochemistry, Qingdao University, Qingdao, China

    Cuncun Yang & Lin Hou

  4. Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, China

    Jing Li

Authors
  1. Lu Zhang
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  2. Fei Zhao
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  4. Qian Tang
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  5. Ru Zhang
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  9. Shiguo Liu
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Correspondence to Lin Hou or Shiguo Liu.

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The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of the Affiliated Hospital of Qingdao University and written consent was obtained from all of the pregnancies before the collection of the placenta and blood.

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Zhang, L., Zhao, F., Yang, C. et al. Hypomethylation of CTGF Promoter in Placenta and Peripheral Blood of Pre-eclampsia Women. Reprod. Sci. 27, 468–476 (2020). https://doi.org/10.1007/s43032-019-00038-z

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  • DOI: https://doi.org/10.1007/s43032-019-00038-z

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