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Circular RNA expression profiling in the fetal side of placenta from maternal polycystic ovary syndrome and circ_0023942 inhibits the proliferation of human ovarian granulosa cell

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Circular RNAs (circRNAs) are widely expressed noncoding RNAs which play important roles in various processes. The present study aimed to explore the effect of maternal PCOS on the expression of circRNAs in fetus and assessed the potential role of circRNA in human ovarian granulosa cell proliferation.

Methods

Total RNA was extracted from the fetal side of placental tissues from maternal PCOS (n = 3) and healthy puerpera (n = 3) for circRNA microarray. Real-time reverse transcriptase quantitative PCR (RT-qPCR) was used to validate the microarray data in fetal side of placental tissues from puerpera with (n = 18) and without (n = 30) PCOS. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to predict the functions and pathways of circ_0023942 host genes. The circRNA-miRNA-mRNA network was constructed through bioinformatics prediction. Circ_0023942 overexpression vector was transiently transfected into human ovarian granulosa cell lines KGN and COV434. Cell proliferation was detected by cell counting kit-8. The protein expression level was determined by western blot.

Results

Compared with healthy puerpera, 14 circRNAs were significantly upregulated and 101 circRNAs were significantly downregulated in the fetal side of placenta from maternal PCOS according to the microarray data. Six differentially expressed circRNAs were selected for validation by RT-qPCR, and the expression patterns of circ_0023942, circ_0002151, circ_0001274, and circ_0008514 were consistent with the microarray data. Circ_0023942 was chosen for further investigation. GO and KEGG analysis predicted that circ_0023942 participated in the regulation of developmental process and the MAPK signaling pathway. Seven miRNAs were predicted to be the targets of circ_0023942. Overexpression of circ_0023942 inhibited human ovarian granulosa cell proliferation and suppressed the expression of CDK-4.

Conclusion

Maternal PCOS impairs circ_0023942 expression in fetus. Overexpression of circ_0023942 inhibits human ovarian granulosa cell proliferation possibly via regulating CDK-4.

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Funding

This work was funded by Medical Research Grant of Jiangsu Commission of Health (H2017043) and Clinical Medical Technology and Development Grant Jiangsu University (JLY20180207).

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Authors and Affiliations

  1. Central Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, 211100, Jiangsu, China

    Chengcheng Zhao, Yu Zhou, Yingfei Lu, Chao Fang & Jianquan Chen

  2. Department of Gynecology and Obstetrics, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, 211100, Jiangsu, China

    Yu Zhou, Xia Shen, Min Gong, Jianquan Chen & Rong Ju

Authors
  1. Chengcheng Zhao
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  2. Yu Zhou
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  3. Xia Shen
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Contributions

ZCC: funding acquisition, project development, data collection, data analysis, manuscript writing, writing-original draft preparation, and writing-review and editing. ZY: data analysis, manuscript editing, funding acquisition, formal analysis, and investigation. SX and GM: sample collection and supervision. LYF and FC: data analysis. CJQ: manuscript editing, formal analysis, and investigation. JR: resources, funding acquisition, project development, manuscript editing, methodology, and supervision.

Corresponding author

Correspondence to Rong Ju.

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The authors declare they have no conflict of interest.

Ethical approval

This study was approved by the Ethics Committee of Nanjing Jiangning hospital (Ethics No. 20170124). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Zhao, C., Zhou, Y., Shen, X. et al. Circular RNA expression profiling in the fetal side of placenta from maternal polycystic ovary syndrome and circ_0023942 inhibits the proliferation of human ovarian granulosa cell. Arch Gynecol Obstet 301, 963–971 (2020). https://doi.org/10.1007/s00404-020-05495-5

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