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Article

Cellular, Extracellular and Extracellular Vesicular miRNA Profiles of Pre-Ovulatory Follicles Indicate Signaling Disturbances in Polycystic Ovaries

1
Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, 12618 Tallinn, Estonia
2
Competence Centre on Health Technologies, Teaduspargi 13, 50411 Tartu, Estonia
3
Department of Pathophysiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14B, 50411 Tartu, Estonia
4
Nova Vita Clinic, A. H. Tammsaare tee 47, 11314 Tallinn, Estonia
5
Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima St. 10, 10-748 Olsztyn, Poland
6
Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, Fr. R. Kreutzwaldi 1, 51006 Tartu, Estonia
7
Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tartu, L. Puusepa St. 8, 50406 Tartu, Estonia
8
Institute of Genomics, University of Tartu, Riia 23b, 51010 Tartu, Estonia
9
Academic Unit of Reproductive and Developmental Medicine, Department of Oncology and Metabolism, The Medical School, University of Sheffield, Sheffield S10 2SF, UK
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(24), 9550; https://doi.org/10.3390/ijms21249550
Received: 18 November 2020 / Revised: 11 December 2020 / Accepted: 13 December 2020 / Published: 15 December 2020
(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function 2020)
Cell-free RNAs have the potential to act as a means of gene expression regulation between cells and are therefore used as diagnostic markers describing the state of tissue environment. The origin and functions of such RNAs in human ovarian follicle, the environment of oocyte maturation, are unclear. The current study investigates the difference in the microRNA profiles of fertile women and polycystic ovary syndrome (PCOS) patients in three compartments from the same preovulatory follicle: mural granulosa cells (MGC), cell-free follicular fluid (FF), and extracellular vesicles (EV) of the FF by small RNA sequencing. In silico analysis was used for the prediction and over-representation of targeted pathways for the detected microRNAs. PCOS follicles were distinguished from normal tissue by the differential expression of 30 microRNAs in MGC and 10 microRNAs in FF (FDR < 0.1) that commonly regulate cytokine signaling pathways. The concentration of EV-s was higher in the FF of PCOS patients (p = 0.04) containing eight differentially expressed microRNAs (p < 0.05). In addition, we present the microRNA profiles of MGC, FF, and EV in the fertile follicle and demonstrate that microRNAs loaded into EVs target mRNAs of distinct signaling pathways in comparison to microRNAs in FF. To conclude, the three follicular compartments play distinct roles in the signaling disturbances associated with PCOS. View Full-Text
Keywords: extracellular vesicles; human ovarian follicle; granulosa cells; follicular fluid; polycystic ovary syndrome; PCOS; miRNA; intercellular communication extracellular vesicles; human ovarian follicle; granulosa cells; follicular fluid; polycystic ovary syndrome; PCOS; miRNA; intercellular communication
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MDPI and ACS Style

Rooda, I.; Hasan, M.M.; Roos, K.; Viil, J.; Andronowska, A.; Smolander, O.-P.; Jaakma, Ü.; Salumets, A.; Fazeli, A.; Velthut-Meikas, A. Cellular, Extracellular and Extracellular Vesicular miRNA Profiles of Pre-Ovulatory Follicles Indicate Signaling Disturbances in Polycystic Ovaries. Int. J. Mol. Sci. 2020, 21, 9550. https://doi.org/10.3390/ijms21249550

AMA Style

Rooda I, Hasan MM, Roos K, Viil J, Andronowska A, Smolander O-P, Jaakma Ü, Salumets A, Fazeli A, Velthut-Meikas A. Cellular, Extracellular and Extracellular Vesicular miRNA Profiles of Pre-Ovulatory Follicles Indicate Signaling Disturbances in Polycystic Ovaries. International Journal of Molecular Sciences. 2020; 21(24):9550. https://doi.org/10.3390/ijms21249550

Chicago/Turabian Style

Rooda, Ilmatar, Mohammad M. Hasan, Kristine Roos, Janeli Viil, Aneta Andronowska, Olli-Pekka Smolander, Ülle Jaakma, Andres Salumets, Alireza Fazeli, and Agne Velthut-Meikas. 2020. "Cellular, Extracellular and Extracellular Vesicular miRNA Profiles of Pre-Ovulatory Follicles Indicate Signaling Disturbances in Polycystic Ovaries" International Journal of Molecular Sciences 21, no. 24: 9550. https://doi.org/10.3390/ijms21249550

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