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Dynamic Changes of Fetal-Derived Hypermethylated RASSF1A and Septin 9 Sequences in Maternal Plasma

  • Maternal Fetal Medicine/Biology: Original Article
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Abstract

DNA methylation has a tissue-specific feature, and placenta has distinct methylation patterns from peripheral blood cells. Although fetal/placental-derived cell free DNA (cfDNA) in the maternal blood has been reported in recent decades, systematic exploration of dynamic changes of the placental epigenetic signatures across gestation is lacking. The primary goal of this study was to characterize prenatal and postnatal methylation levels of placental-sourced RASSF1A and Septin 9 sequences in maternal plasma. Here, we used a quantitative methylation-sensitive PCR (qMS-PCR) assay to check the methylation status of RASSF1A and Septin 9 in placental tissues of pregnant women and plasma samples from non-pregnant individuals. Then, we examined the methylation levels of the two targets in maternal plasma from expectant women at different gestational ages and postdelivery. Hypermethylated RASSF1A and Septin 9 were identified in placental samples but undetectable in peripheral blood of healthy non-pregnant women. Further, hypermethylated RASSF1A sequence was found in all three trimesters of pregnancy except for early gestation (8 weeks). Moreover, methylation scores of the two targets increased as pregnancy progressed. In addition, hypermethylated RASSF1A sequence was detectable in maternal plasma from 12 h (one case) to 24 h postdelivery (three cases) in 18 pregnant women. Our data on the variation of fetal-sourced methylated RASSF1A levels in maternal plasma in relation to gestational age provide a useful basis for improving the reliability of the methylation assay for non-invasive prenatal diagnosis (NIPD) in clinical practice.

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Funding

This study was supported by the Medical Scientific Research Foundation of Guangdong Province of China (No. A2020245).

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Authors and Affiliations

  1. Department of Obstetrics, Guangdong Women and Children Hospital, Guangzhou, 511400, China

    Li Zhang, Chen-mei-yi Wang & Guo-cheng Liu

  2. Translational Medicine Center, Guangdong Women and Children Hospital, Guangzhou, 511400, China

    Wei-ping Zhou, Qiu-ping Chen, Shuai Zhou, Wen Lei, Hua Deng & Liang Zhang

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  1. Li Zhang
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  2. Chen-mei-yi Wang
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  8. Liang Zhang
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Correspondence to Liang Zhang or Guo-cheng Liu.

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Zhang, L., Wang, Cmy., Zhou, Wp. et al. Dynamic Changes of Fetal-Derived Hypermethylated RASSF1A and Septin 9 Sequences in Maternal Plasma. Reprod. Sci. 28, 1194–1199 (2021). https://doi.org/10.1007/s43032-020-00416-y

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  • DOI: https://doi.org/10.1007/s43032-020-00416-y

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