circRNA-Mediated Inhibin–Activin Balance Regulation in Ovarian Granulosa Cell Apoptosis and Follicular Atresia

Ma, Mengnan; Wang, Huiming; Zhang, Yi; Zhang, Jinbi; Liu, Jingge; Pan, Zengxiang

doi:10.3390/ijms22179113

Open AccessArticle

circRNA-Mediated Inhibin–Activin Balance Regulation in Ovarian Granulosa Cell Apoptosis and Follicular Atresia

by

Mengnan Ma

¹,

Huiming Wang

¹,

Yi Zhang

¹,

Jinbi Zhang

²,

Jingge Liu

² and

Zengxiang Pan

^1,*

¹

College of Animal Science and Technology, Nanjing Agriculture University, Nanjing 210095, China

²

College of Animal Science and Food Engineering, Jinling Institute of Technology, Nanjing 211169, China

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2021, 22(17), 9113; https://doi.org/10.3390/ijms22179113

Submission received: 5 August 2021 / Revised: 20 August 2021 / Accepted: 20 August 2021 / Published: 24 August 2021

(This article belongs to the Special Issue Cell Apoptosis)

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Abstract

Ovarian granulosa cells (GC) play an essential role in the development and atresia of follicles. Emerging studies suggest that non-coding RNAs are involved in the regulation of GC apoptosis. Here, we aimed to analyze the function of ssc-circINHA-001, coded by the first exon of the inhibin subunit α gene (INHA), in resisting GC apoptosis and follicular atresia by enhancing the expression of the inhibin subunit β A (INHBA) through a cluster of miRNAs. A higher expression of ssc-circINHA-001 in healthy follicles compared to early atretic follicles was detected by qRT-PCR. Its circular structure was confirmed by RNase R treatment and reversed PCR. The function of ssc-circINHA-001 in GC resistance to apoptosis was detected by in vitro transfection of its si-RNA. Furthermore, the dual-luciferase reporter assay suggested that ssc-circINHA-001 adsorbed three miRNAs, termed miR-214-5p, miR-7144-3p, and miR-9830-5p, which share the common target INHBA. A low expression of ssc-circINHA-001 increased the levels of the free miRNAs, inhibited INHBA expression, and thus raised GCs apoptosis through a shift from the secretion of activin to that of inhibin. Our study demonstrated the existence of a circRNA–microRNAs–INHBA regulatory axis in follicular GC apoptosis and provides insight into the relationship between circRNA function and its coding gene in inhibin/activin balance and ovarian physiological functions.

Keywords: granulosa cell apoptosis; circRNA; miRNA; INHA; INHBA; inhibin; activin

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MDPI and ACS Style

Ma, M.; Wang, H.; Zhang, Y.; Zhang, J.; Liu, J.; Pan, Z. circRNA-Mediated Inhibin–Activin Balance Regulation in Ovarian Granulosa Cell Apoptosis and Follicular Atresia. Int. J. Mol. Sci. 2021, 22, 9113. https://doi.org/10.3390/ijms22179113

AMA Style

Ma M, Wang H, Zhang Y, Zhang J, Liu J, Pan Z. circRNA-Mediated Inhibin–Activin Balance Regulation in Ovarian Granulosa Cell Apoptosis and Follicular Atresia. International Journal of Molecular Sciences. 2021; 22(17):9113. https://doi.org/10.3390/ijms22179113

Chicago/Turabian Style

Ma, Mengnan, Huiming Wang, Yi Zhang, Jinbi Zhang, Jingge Liu, and Zengxiang Pan. 2021. "circRNA-Mediated Inhibin–Activin Balance Regulation in Ovarian Granulosa Cell Apoptosis and Follicular Atresia" International Journal of Molecular Sciences 22, no. 17: 9113. https://doi.org/10.3390/ijms22179113

APA Style

Ma, M., Wang, H., Zhang, Y., Zhang, J., Liu, J., & Pan, Z. (2021). circRNA-Mediated Inhibin–Activin Balance Regulation in Ovarian Granulosa Cell Apoptosis and Follicular Atresia. International Journal of Molecular Sciences, 22(17), 9113. https://doi.org/10.3390/ijms22179113

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circRNA-Mediated Inhibin–Activin Balance Regulation in Ovarian Granulosa Cell Apoptosis and Follicular Atresia

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