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The regulatory role of miR-20a in bovine cumulus cells and its contribution to oocyte maturation

Published online by Cambridge University Press:  23 April 2021

Eryk Andreas
Affiliation:
Institute of Animal Science, Animal Breeding and Husbandry Group, University of Bonn, 53115Bonn, Germany Robinson Research Institute, The University of Adelaide, 5000Adelaide, SA, Australia
Hari Om Pandey
Affiliation:
Institute of Animal Science, Animal Breeding and Husbandry Group, University of Bonn, 53115Bonn, Germany
Michael Hoelker
Affiliation:
Institute of Animal Science, Animal Breeding and Husbandry Group, University of Bonn, 53115Bonn, Germany
Dessie Salilew-Wondim
Affiliation:
Institute of Animal Science, Animal Breeding and Husbandry Group, University of Bonn, 53115Bonn, Germany
Samuel Gebremedhn
Affiliation:
Institute of Animal Science, Animal Breeding and Husbandry Group, University of Bonn, 53115Bonn, Germany Department of Biomedical Sciences, Animal Reproduction and Biotechnology Laboratory, Colorado State University, 3105 Rampart Rd, Fort Collins, CO80521, USA
Karl Schellander
Affiliation:
Institute of Animal Science, Animal Breeding and Husbandry Group, University of Bonn, 53115Bonn, Germany
Dawit Tesfaye*
Affiliation:
Institute of Animal Science, Animal Breeding and Husbandry Group, University of Bonn, 53115Bonn, Germany Department of Biomedical Sciences, Animal Reproduction and Biotechnology Laboratory, Colorado State University, 3105 Rampart Rd, Fort Collins, CO80521, USA
*
Author for correspondence: Dawit Tesfaye. Department of Biomedical Sciences, Animal Reproduction and Biotechnology Laboratory, 3105 Rampart Rd, Fort Collins, CO, USA. Tel: +1 970 491 8391. E-mail: Dawit.Tesfaye@colostate.edu

Summary

Dynamic changes in microRNAs in oocyte and cumulus cells before and after maturation may explain the spatiotemporal post-transcriptional gene regulation within bovine follicular cells during the oocyte maturation process. miR-20a has been previously shown to regulate proliferation and differentiation as well as progesterone levels in cultured bovine granulosa cells. In the present study, we aimed to demonstrate the function of miR-20a during the bovine oocyte maturation process. Maturation of cumulus–oocyte complexes (COCs) was performed at 39°C in an humidified atmosphere with 5% CO2 in air. The expression of miR-20a was investigated in the cumulus cells and oocytes at 22 h post culture. The functional role of miR-20a was examined by modulating the expression of miR-20a in COCs during in vitro maturation (IVM). We found that the miR-20a expression was increased in cumulus cells but decreased in oocytes after IVM. Overexpression of miR-20a increased the oocyte maturation rate. Even though not statistically significant, miR-20a overexpression during IVM increased progesterone levels in the spent medium. This was further supported by the expression of STAR and CYP11A1 genes in cumulus cells. The phenotypes observed due to overexpression of miR-20a were validated by BMP15 supplementation during IVM and subsequent transfection of BMP15-treated COCs using miR-20a mimic or BMPR2 siRNA. We found that miR-20a mimic or BMPR2 siRNA transfection rescued BMP15-reduced oocyte maturation and progesterone levels. We concluded that miR-20a regulates oocyte maturation by increasing cumulus cell progesterone synthesis by simultaneous suppression of BMPR2 expression.

Type
Research Article
Copyright
© University of Bonn, 2021. Published by Cambridge University Press

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References

Abd El Naby, WS, Hagos, TH, Hossain, MM, Salilew-Wondim, D, Gad, AY, Rings, F, Cinar, MU, Tholen, E, Looft, C, Schellander, K, Hoelker, M and Tesfaye, D (2013). Expression analysis of regulatory microRNAs in bovine cumulus oocyte complex and preimplantation embryos. Zygote 21, 3151.CrossRefGoogle ScholarPubMed
Andreas, E, Hoelker, M, Neuhoff, C, Tholen, E, Schellander, K, Tesfaye, D and Salilew-Wondim, D (2016). MicroRNA 17–92 cluster regulates proliferation and differentiation of bovine granulosa cells by targeting PTEN and BMPR2 genes. Cell Tissue Res 366, 219–30.CrossRefGoogle ScholarPubMed
Aparicio, IM, Garcia-Herreros, M, O’Shea, LC, Hensey, C, Lonergan, P and Fair, T (2011). Expression, regulation, and function of progesterone receptors in bovine cumulus oocyte complexes during in vitro maturation. Biol Reprod 84, 910–21.CrossRefGoogle ScholarPubMed
Assidi, M, Dieleman, SJ and Sirard, MA (2010). Cumulus cell gene expression following the LH surge in bovine preovulatory follicles: potential early markers of oocyte competence. Reproduction 140, 835–52.CrossRefGoogle ScholarPubMed
Atef, A, Francois, P, Christian, V and Marc-Andre, S (2005). The potential role of gap junction communication between cumulus cells and bovine oocytes during in vitro maturation. Mol Reprod Dev 71, 358–67.CrossRefGoogle ScholarPubMed
Buccione, R, Schroeder, AC and Eppig, JJ (1990a). Interactions between somatic cells and germ cells throughout mammalian oogenesis. Biol Reprod 43, 543–7.CrossRefGoogle ScholarPubMed
Buccione, R, Vanderhyden, BC, Caron, PJ and Eppig, JJ (1990b). FSH-induced expansion of the mouse cumulus oophorus in vitro is dependent upon a specific factor(s). secreted by the oocyte. Dev Biol 138, 1625.CrossRefGoogle ScholarPubMed
Chang, HM, Cheng, JC, Klausen, C and Leung, PC (2013). BMP15 suppresses progesterone production by down-regulating StAR via ALK3 in human granulosa cells. Mol Endocrinol 27, 2093–104.CrossRefGoogle ScholarPubMed
Chen, J, Torcia, S, Xie, F, Lin, CJ, Cakmak, H, Franciosi, F, Horner, K, Onodera, C, Song, JS, Cedars, MI, Ramalho-Santos, M and Conti, M (2013). Somatic cells regulate maternal mRNA translation and developmental competence of mouse oocytes. Nat Cell Biol 15, 1415–23.CrossRefGoogle ScholarPubMed
Choi, YH, Carnevale, EM, Seidel, GE Jr and Squire, EL (2001). Effects of gonadotropins on bovine oocytes matured in TCM-199. Theriogenology 56, 661–70.CrossRefGoogle ScholarPubMed
Dai, A, Sun, H, Fang, T, Zhang, Q, Wu, S, Jiang, Y, Ding, L, Yan, G and Hu, Y (2013). MicroRNA-133b stimulates ovarian estradiol synthesis by targeting Foxl2. FEBS Lett 587, 2474–82.CrossRefGoogle ScholarPubMed
Eppig, JJ (2001). Oocyte control of ovarian follicular development and function in mammals. Reproduction 122, 829–38.CrossRefGoogle ScholarPubMed
Eppig, JJ, Wigglesworth, K, Pendola, F and Hirao, Y (1997). Murine oocytes suppress expression of luteinizing hormone receptor messenger ribonucleic acid by granulosa cells. Biol Reprod 56, 976–84.CrossRefGoogle ScholarPubMed
Eppig, JJ, Pendola, FL, Wigglesworth, K and Pendola, JK (2005). Mouse oocytes regulate metabolic cooperativity between granulosa cells and oocytes: amino acid transport. Biol Reprod 73, 351–7.CrossRefGoogle ScholarPubMed
Fair, T, Carter, F, Park, S, Evans, AC and Lonergan, P (2007). Global gene expression analysis during bovine oocyte in vitro maturation. Theriogenology 68 (Suppl 1), S917.CrossRefGoogle ScholarPubMed
Gebremedhn, S, Salilew-Wondim, D, Ahmad, I, Sahadevan, S, Hossain, MM, Hoelker, M, Rings, F, Neuhoff, C, Tholen, E, Looft, C, Schellander, K and Tesfaye, D (2015). MicroRNA expression profile in bovine granulosa cells of preovulatory dominant and subordinate follicles during the late follicular phase of the estrous cycle. PLoS One 10, e0125912.CrossRefGoogle ScholarPubMed
Gilchrist, RB, Ritter, LJ and Armstrong, DT (2001). Mouse oocyte mitogenic activity is developmentally coordinated throughout folliculogenesis and meiotic maturation. Dev Biol 240, 289–98.CrossRefGoogle ScholarPubMed
Gilchrist, RB, Morrissey, MP, Ritter, LJ and Armstrong, DT (2003). Comparison of oocyte factors and transforming growth factor-beta in the regulation of DNA synthesis in bovine granulosa cells. Mol Cell Endocrinol 201(1–2), 8795.CrossRefGoogle ScholarPubMed
Gilchrist, RB, Ritter, LJ and Armstrong, DT (2004). Oocyte-somatic cell interactions during follicle development in mammals. Anim Reprod Sci 83, 431–46.CrossRefGoogle Scholar
Gilchrist, RB, Ritter, LJ, Myllymaa, S, Kaivo-Oja, N, Dragovic, RA, Hickey, TE, Ritvos, O and Mottershead, DG (2006). Molecular basis of oocyte-paracrine signalling that promotes granulosa cell proliferation. J Cell Sci 119(Pt 18), 3811–21.CrossRefGoogle ScholarPubMed
Grimes, RW and Ireland, JJ (1986). Relationship of macroscopic appearance of the surface of bovine ovarian follicles concentrations of steroids in follicular fluid, and maturation of oocytes in vitro . Biol Reprod 35, 725–32.CrossRefGoogle ScholarPubMed
Hosoya, T, Otsuka, F, Nakamura, E, Terasaka, T, Inagaki, K, Tsukamoto-Yamauchi, N, Hara, T, Toma, K, Komatsubara, M and Makino, H (2015). Regulatory role of BMP-9 in steroidogenesis by rat ovarian granulosa cells. J Steroid Biochem Mol Biol 147, 8591.CrossRefGoogle ScholarPubMed
Hussein, TS, Froiland, DA, Amato, F, Thompson, JG and Gilchrist, RB (2005). Oocytes prevent cumulus cell apoptosis by maintaining a morphogenic paracrine gradient of bone morphogenetic proteins. J Cell Sci 118(Pt 22), 5257–68.CrossRefGoogle ScholarPubMed
Jamnongjit, M, Gill, A and Hammes, SR (2005). Epidermal growth factor receptor signaling is required for normal ovarian steroidogenesis and oocyte maturation. Proc Natl Acad Sci USA 102, 16257–62.CrossRefGoogle ScholarPubMed
Ježová, M, Scsuková, S, Nagyová, E, Vranová, J, Procházka, R and Kolena, J (2001). Effect of intraovarian factors on porcine follicular cells: cumulus expansion, granulosa and cumulus cell progesterone production. Anim Reprod Sci 65(1–2), 115–26.CrossRefGoogle ScholarPubMed
Jiang, L, Huang, J, Li, L, Chen, Y, Chen, X, Zhao, X and Yang, D (2015). MicroRNA-93 promotes ovarian granulosa cells proliferation through targeting CDKN1A in polycystic ovarian syndrome. J Clin Endocrinol Metab 100, 20143827.CrossRefGoogle ScholarPubMed
Joyce, IM, Clark, AT, Pendola, FL and Eppig, JJ (2000). Comparison of recombinant growth differentiation factor-9 and oocyte regulation of KIT ligand messenger ribonucleic acid expression in mouse ovarian follicles. Biol Reprod 63, 1669–75.CrossRefGoogle ScholarPubMed
Kawashima, I, Okazaki, T, Noma, N, Nishibori, M, Yamashita, Y and Shimada, M (2008). Sequential exposure of porcine cumulus cells to FSH and/or LH is critical for appropriate expression of steroidogenic and ovulation-related genes that impact oocyte maturation in vivo and in vitro . Reproduction 136, 921.CrossRefGoogle ScholarPubMed
Labrecque, R and Sirard, M-A (2014). The study of mammalian oocyte competence by transcriptome analysis: progress and challenges. Mol Hum Reprod 20, 103–16.CrossRefGoogle Scholar
Li, R, Norman, RJ, Armstrong, DT and Gilchrist, RB (2000). Oocyte-secreted factor(s) determine functional differences between bovine mural granulosa cells and cumulus cells. Biol Reprod 63, 839–45.CrossRefGoogle ScholarPubMed
Livak, KJ and Schmittgen, TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2–DDCT method. Methods 25, 402–8.CrossRefGoogle Scholar
Luo, W, Zhao, X, Jin, H, Tao, L, Zhu, J, Wang, H, Hemmings, BA and Yang, Z (2015). AKT1 signaling coordinates BMP signaling and β-catenin activity to regulate second heart field progenitor development. Development 142, 732–42.CrossRefGoogle ScholarPubMed
Matzuk, MM, Burns, KH, Viveiros, MM and Eppig, JJ (2002). Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science 296(5576), 2178–80.CrossRefGoogle ScholarPubMed
Mingoti, GZ, Garcia, JM and Rosa-e-Silva, AAM (2002). Steroidogenesis in cumulus cells of bovine cumulus–oocyte-complexes matured in vitro with BSA and different concentrations of steroids. Anim Reprod Sci 69(3–4), 175–86.CrossRefGoogle ScholarPubMed
Montano, E, Olivera, M and Ruiz-Cortes, ZT (2009). Association between leptin, LH and its receptor and luteinization and progesterone accumulation (P4). in bovine granulosa cell in vitro . Reprod Domest Anim 44, 699704.CrossRefGoogle ScholarPubMed
Nagyová, E, Camaioni, A, Scsuková, S, Mlynarcikova, A, Procházka, R, Nemcova, L and Salustri, A (2011). Activation of cumulus cell SMAD2/3 and epidermal growth factor receptor pathways are involved in porcine oocyte–cumulus cell expansion and steroidogenesis. Mol Reprod Dev 78, 391402.CrossRefGoogle ScholarPubMed
Nagyová, E, Scsuková, S, Nemcova, L, Mlynarcikova, A, Yi, YJ, Sutovsky, M and Sutovsky, P (2012). Inhibition of proteasomal proteolysis affects expression of extracellular matrix components and steroidogenesis in porcine oocyte–cumulus complexes. Domest Anim Endocrinol 42, 5062.CrossRefGoogle ScholarPubMed
Nivet, AL, Vigneault, C, Blondin, P and Sirard, MA (2013). Changes in granulosa cells’ gene expression associated with increased oocyte competence in bovine. Reproduction 145, 555–65.CrossRefGoogle ScholarPubMed
Nuttinck, F, Guienne, BM-L, Clément, L, Reinaud, P, Charpigny, G and Grimard, B (2008). Expression of genes involved in prostaglandin E2 and progesterone production in bovine cumulus–oocyte complexes during in vitro maturation and fertilization. Reproduction 135, 593603.CrossRefGoogle ScholarPubMed
O’Shea, LC, Hensey, C and Fair, T (2013). Progesterone regulation of AVEN protects bovine oocytes from apoptosis during meiotic maturation. Biol Reprod 89, 146.Google ScholarPubMed
Otsuka, F and Shimasaki, S (2002). A negative feedback system between oocyte bone morphogenetic protein 15 and granulosa cell kit ligand: its role in regulating granulosa cell mitosis. Proc Natl Acad Sci USA 99, 8060–5.CrossRefGoogle ScholarPubMed
Pan, B, Toms, D, Shen, W and Li, J (2015). MicroRNA-378 regulates oocyte maturation via the suppression of aromatase in porcine cumulus cells. Am J Physiol Endocrinol Metab 308, 27.CrossRefGoogle ScholarPubMed
Panigone, S, Hsieh, M, Fu, M, Persani, L and Conti, M (2008). Luteinizing hormone signaling in preovulatory follicles involves early activation of the epidermal growth factor receptor pathway. Mol Endocrinol 22, 924–36.CrossRefGoogle ScholarPubMed
Picton, H, Briggs, D and Gosden, R (1998). The molecular basis of oocyte growth and development. Mol Cell Endocrinol 145(1–2), 2737.CrossRefGoogle ScholarPubMed
Regassa, A, Rings, F, Hoelker, M, Cinar, U, Tholen, E, Looft, C, Schellander, K and Tesfaye, D (2011). Transcriptome dynamics and molecular cross-talk between bovine oocyte and its companion cumulus cells. BMC Genomics 12, 14712164.CrossRefGoogle ScholarPubMed
Roh, SI, Batten, BE, Friedman, CI and Kim, MH (1988). The effects of progesterone antagonist RU 486 on mouse oocyte maturation, ovulation, fertilization, and cleavage. Am J Obstet Gynecol 159, 1584–9.CrossRefGoogle ScholarPubMed
Sanchez, F and Smitz, J (2012). Molecular control of oogenesis. Biochim Biophys Acta 12(912), 24.Google Scholar
Shao, R, Markstrom, E, Friberg, PA, Johansson, M and Billig, H (2003). Expression of progesterone receptor (PR) A and B isoforms in mouse granulosa cells: stage-dependent PR-mediated regulation of apoptosis and cell proliferation. Biol Reprod 68, 914–21.CrossRefGoogle Scholar
Shimada, M and Terada, T (2002). FSH and LH induce progesterone production and progesterone receptor synthesis in cumulus cells: a requirement for meiotic resumption in porcine oocytes. Mol Hum Reprod 8, 612–8.CrossRefGoogle ScholarPubMed
Shimada, M, Nishibori, M, Yamashita, Y, Ito, J, Mori, T and Richards, JS (2004a). Down-regulated expression of a disintegrin and metalloproteinase with thrombospondin-like repeats-1 by progesterone receptor antagonist is associated with impaired expansion of porcine cumulus–oocyte complexes. Endocrinology 145, 4603–14.CrossRefGoogle Scholar
Shimada, M, Yamashita, Y, Ito, J, Okazaki, T, Kawahata, K and Nishibori, M (2004b). Expression of two progesterone receptor isoforms in cumulus cells and their roles during meiotic resumption of porcine oocytes. J Mol Endocrinol 33, 209–25.CrossRefGoogle ScholarPubMed
Shimada, M, Yamashita, Y, Ito, J, Okazaki, T, Kawahata, K and Nishibori, M (2004c). Expression of two progesterone receptor isoforms in cumulus cells and their roles during meiotic resumption of porcine oocytes. J Mol Endocrinol 33, 209–25.CrossRefGoogle ScholarPubMed
Siqueira, LC, Barreta, MH, Gasperin, B, Bohrer, R, Santos, JT, Buratini, J Jr, Oliveira, JF and Goncalves, PB (2012). Angiotensin II, progesterone, and prostaglandins are sequential steps in the pathway to bovine oocyte nuclear maturation. Theriogenology 77, 1779–87.CrossRefGoogle ScholarPubMed
Sirotkin, AV (1992). Involvement of steroid hormones in bovine oocytes maturation in vitro . J Steroid Biochem Mol Biol 41(3–8), 855–8.CrossRefGoogle ScholarPubMed
Sugiura, K, Pendola, FL and Eppig, JJ (2005). Oocyte control of metabolic cooperativity between oocytes and companion granulosa cells: energy metabolism. Dev Biol 279, 2030.CrossRefGoogle ScholarPubMed
Takahashi, T, Morrow, JD, Wang, H and Dey, SK (2006). Cyclooxygenase-2-derived prostaglandin E2 directs oocyte maturation by differentially influencing multiple signaling pathways. J Biol Chem 281, 37117–29.CrossRefGoogle ScholarPubMed
Tanghe, S, Van Soom, A, Nauwynck, H, Coryn, M and de Kruif, A (2002). Minireview: Functions of the cumulus oophorus during oocyte maturation, ovulation, and fertilization. Mol Reprod Dev 61, 414–24.CrossRefGoogle ScholarPubMed
Tesfaye, D, Worku, D, Rings, F, Phatsara, C, Tholen, E, Schellander, K and Hoelker, M (2009). Identification and expression profiling of microRNAs during bovine oocyte maturation using heterologous approach. Mol Reprod Dev 76, 665–77.CrossRefGoogle ScholarPubMed
van Tol, HT, van Eijk, MJ, Mummery, CL, van den Hurk, R and Bevers, MM (1996). Influence of FSH and hCG on the resumption of meiosis of bovine oocytes surrounded by cumulus cells connected to membrana granulosa. Mol Reprod Dev 45, 218–24.3.0.CO;2-X>CrossRefGoogle ScholarPubMed
Vanderhyden, BC, Caron, PJ, Buccione, R and Eppig, JJ (1990). Developmental pattern of the secretion of cumulus expansion-enabling factor by mouse oocytes and the role of oocytes in promoting granulosa cell differentiation. Dev Biol 140, 307–17.CrossRefGoogle ScholarPubMed
Vozzi, C, Formenton, A, Chanson, A, Senn, A, Sahli, R, Shaw, P, Nicod, P, Germond, M and Haefliger, JA (2001). Involvement of connexin 43 in meiotic maturation of bovine oocytes. Reproduction 122, 619–28.CrossRefGoogle ScholarPubMed
Wang, C, Li, D, Zhang, S, Xing, Y, Gao, Y and Wu, J (2016). MicroRNA-125a-5p induces mouse granulosa cell apoptosis by targeting signal transducer and activator of transcription 3. Menopause 23, 100–7.CrossRefGoogle ScholarPubMed
Wang, HF, Isobe, N, Kumamoto, K, Yamashiro, H, Yamashita, Y and Terada, T (2006). Studies of the role of steroid hormone in the regulation of oocyte maturation in cattle. Reprod Biol Endocrinol 4, 4.CrossRefGoogle ScholarPubMed
Xu, YW, Wang, B, Ding, CH, Li, T, Gu, F and Zhou, C (2011). Differentially expressed micoRNAs in human oocytes. J Assist Reprod Genet 28, 559–66.CrossRefGoogle ScholarPubMed
Yamashita, Y, Shimada, M, Okazaki, T, Maeda, T and Terada, T (2003). Production of progesterone from de novo-synthesized cholesterol in cumulus cells and its physiological role during meiotic resumption of porcine oocytes. Biol Reprod 68, 1193–8.CrossRefGoogle ScholarPubMed
Yao, G, Liang, M, Liang, N, Yin, M, Lu, M, Lian, J, Wang, Y and Sun, F (2014). MicroRNA-224 is involved in the regulation of mouse cumulus expansion by targeting Ptx3. Mol Cell Endocrinol 382, 244–53.CrossRefGoogle ScholarPubMed
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