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. 2020 Apr;301(4):963-971.
doi: 10.1007/s00404-020-05495-5. Epub 2020 Mar 19.

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

Chengcheng Zhao  1 , Yu Zhou  1   2 , Xia Shen  2 , Min Gong  2 , Yingfei Lu  1 , Chao Fang  1 , Jianquan Chen  1   2 , Rong Ju  3
Affiliations

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

Chengcheng Zhao et al. Arch Gynecol Obstet. 2020 Apr.

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.

Keywords: Ovarian granulosa cell; PCOS; Proliferation; circ_0023942.

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