MicroRNA indicators of follicular steroidogenesis
F. X. Donadeu A C , S. D. Sontakke A B and J. Ioannidis AA The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
B Present address: Laboratory for Conservation of Endangered Species (LaCONES) CSIR-Centre for Cellular and Molecular Biology, Attapur Ring Road, Hyderabad, 500048, India.
C Corresponding author. Email: xavier.donadeu@roslin.ed.ac.uk
Reproduction, Fertility and Development 29(5) 906-912 https://doi.org/10.1071/RD15282
Submitted: 13 July 2015 Accepted: 18 December 2015 Published: 11 February 2016
Abstract
MicroRNAs (miRNAs) can provide useful biomarkers of tissue function. The aim of the present study was to determine, in bovine follicles (n = 66; diameter 4–22 mm), the relationship among several indices of steroidogenesis and levels of 15 miRNAs previously identified to be associated with follicle development. Oestradiol levels, the oestradiol : progesterone (E : P) ratio and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) expression were strongly correlated with each other (ρ > 0.8) and with LH/choriogonadotropin receptor (LHCGR) expression (ρ ≥ 0.6; P < 0.01). Levels of nine different miRNAs in the follicular wall were correlated (P < 0.01) with oestradiol, the E : P ratio and CYP19A1, with miR-873 showing the strongest correlation in each case (ρ > 0.7). Analyses of follicular fluid miRNAs identified miR-202 as correlated with oestradiol, the E : P ratio and CYP19A1 (ρ > 0.5; P < 0.01). When considering all follicle end-points together, we found that using a cut-off value of E : P = 1 overestimated the number of oestrogen-inactive follicles, whereas using CYP19A1 as a classifier provided a clearer separation of follicle samples based on oestrogen activity, in agreement with the E : P ratio, LHCGR expression and levels of miR-873 and miR-202. In conclusion, we identified miR-873 and miR-202 as miRNAs whose levels in follicular tissues can be used as indicators of steroidogenic capacity in bovine. We showed that these or other gene expression parameters, in addition or alternatively to the E : P ratio, should be used to accurately classify follicles based on steroidogenic capacity.
Additional keywords: bovine, CYP19A1, E : P ratio, follicle, miR-873, miR-202, miRNA, oestradiol.
References
Bannister, S. C., Smith, C. A., Roeszler, K. N., Doran, T. J., Sinclair, A. H., and Tizard, M. L. V. (2011). Manipulation of estrogen synthesis alters MIR202* expression in embryonic chicken gonads. Biol. Reprod. 85, 22–30.| Manipulation of estrogen synthesis alters MIR202* expression in embryonic chicken gonads.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXotFOlsrg%3D&md5=cdc4d544763e1f9ed0d0d12b8dbfc41aCAS | 21389341PubMed |
Bao, B., and Garverick, H. A. (1998). Expression of steroidogenic enzyme and gonadotropin receptor genes in bovine follicles during ovarian follicular waves: a review. J. Anim. Sci. 76, 1903–1921.
| 1:CAS:528:DyaK1cXkvV2hsLk%3D&md5=2db582294995c4a2fd6bdba3d79e5ca7CAS | 9690647PubMed |
Beg, M. A., and Ginther, O. J. (2006). Follicle selection in cattle and horses: role of intrafollicular factors. Reproduction 132, 365–377.
| Follicle selection in cattle and horses: role of intrafollicular factors.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtFCgt77F&md5=d2e62884bab96cc1ea26d88904e438ecCAS | 16940278PubMed |
Cochrane, D. R., Cittelly, D. M., and Richer, J. K. (2011). Steroid receptors and microRNAs: relationships revealed. Steroids 76, 1–10.
| Steroid receptors and microRNAs: relationships revealed.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsF2gtLjK&md5=abc913e59a6f335d073a15cab355522fCAS | 21093468PubMed |
Cui, J., Bi, M., Overstreet, A. M., Yang, Y., Li, H., Leng, Y., Qian, K., Huang, Q., Zhang, C., Lu, Z., Chen, J., Sun, T., Wu, R., Sun, Y., Song, H., Wei, X., Jing, P., Meredith, A., Yang, X., and Zhang, C. (2014). MiR-873 regulates ER[alpha] transcriptional activity and tamoxifen resistance via targeting CDK3 in breast cancer cells. Oncogene 34, 3895–3907.
| MiR-873 regulates ER[alpha] transcriptional activity and tamoxifen resistance via targeting CDK3 in breast cancer cells.Crossref | GoogleScholarGoogle Scholar | 25531331PubMed |
da Silveira, J. C., Veeramachaneni, D. N., Winger, Q. A., Carnevale, E. M., and Bouma, G. J. (2012). Cell-secreted vesicles in equine ovarian follicular fluid contain miRNAs and proteins: a possible new form of cell communication within the ovarian follicle. Biol. Reprod. 86, 71.
| Cell-secreted vesicles in equine ovarian follicular fluid contain miRNAs and proteins: a possible new form of cell communication within the ovarian follicle.Crossref | GoogleScholarGoogle Scholar | 22116803PubMed |
Donadeu, F. X., Schauer, S. N., and Sontakke, S. D. (2012). Involvement of miRNAs in ovarian follicular and luteal development. J. Endocrinol. 215, 323–334.
| Involvement of miRNAs in ovarian follicular and luteal development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xhsl2it7bO&md5=a0884c1ad25404bf2bc14cb2580390f8CAS | 23038794PubMed |
Ginther, O. J., Beg, M. A., Donadeu, F. X., and Bergfelt, D. R. (2003). Mechanism of follicle deviation in monovular farm species. Anim. Reprod. Sci. 78, 239–257.
| Mechanism of follicle deviation in monovular farm species.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXksF2gtro%3D&md5=aaa7452c0604b3adf853d0117fd51b3fCAS | 12818647PubMed |
Ireland, J. J., Mihm, M., Austin, E., Diskin, M. G., and Roche, J. F. (2000). Historical perspective of turnover of dominant follicles during the bovine estrous cycle: key concepts, studies, advancements, and terms. J. Dairy Sci. 83, 1648–1658.
| Historical perspective of turnover of dominant follicles during the bovine estrous cycle: key concepts, studies, advancements, and terms.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXltVGgtbg%3D&md5=9eb9b6c2a7eb69be1312cd09a693fde5CAS | 10908068PubMed |
Koufaris, C., Papagregoriou, G., Kousoulidou, L., Moutafi, M., Tauber, M., Jouret, B., Kieffer, I., Deltas, C., Tanteles, G. A., Anastasiadou, V., Patsalis, P. C., and Sismani, C. (2015). Haploinsufficiency of the miR-873/miR-876 microRNA cluster is associated with craniofacial abnormalities. Gene 561, 95–100.
| Haploinsufficiency of the miR-873/miR-876 microRNA cluster is associated with craniofacial abnormalities.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXis1SksLk%3D&md5=7ae379c4057234bb285a3690e8c3eb7bCAS | 25680557PubMed |
Li, M.-C., Yu, J.-H., Yu, S.-S., Chi, Y.-Y., and Xiang, Y.-B. (2015). MicroRNA-873 inhibits morphine-induced macrophage apoptosis by elevating A20 expression. Pain Medicine 16, 1993–1999.
| MicroRNA-873 inhibits morphine-induced macrophage apoptosis by elevating A20 expression.Crossref | GoogleScholarGoogle Scholar | 25989384PubMed |
Liu, X., He, F., Pang, R., Zhao, D., Qiu, W., Shan, K., Zhang, J., Lu, Y., Li, Y., and Wang, Y. (2014). Interleukin-17 (IL-17)-induced microRNA 873 (miR-873) contributes to the pathogenesis of experimental autoimmune encephalomyelitis by targeting A20 ubiquitin-editing enzyme. J. Biol. Chem. 289, 28 971–28 986.
| Interleukin-17 (IL-17)-induced microRNA 873 (miR-873) contributes to the pathogenesis of experimental autoimmune encephalomyelitis by targeting A20 ubiquitin-editing enzyme.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhslKrtr7J&md5=75ec97f85b20467ea3c974aad84eb27bCAS |
Schauer, S. N., Sontakke, S. D., Watson, E. D., Esteves, C. L., and Donadeu, F. X. (2013). Involvement of miRNAs in equine follicle development. Reproduction 146, 273–282.
| Involvement of miRNAs in equine follicle development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhsVaiu77E&md5=8b8b611e2bb2e20a7dbdb01ffed65ff0CAS | 23813447PubMed |
Sirotkin, A. V., Lauková, M., Ovcharenko, D., Brenaut, P., and Mlynček, M. (2010). Identification of microRNAs controlling human ovarian cell proliferation and apoptosis. J. Cell. Physiol. 223, 49–56.
| 1:CAS:528:DC%2BC3cXhtlSitrY%3D&md5=6f07fd8d70873858976ba4cf73e5adedCAS | 20039279PubMed |
Sohel, M. M. H., Hoelker, M., Noferesti, S. S., Salilew-Wondim, D., Tholen, E., Looft, C., Rings, F., Uddin, M. J., Spencer, T. E., Schellander, K., and Tesfaye, D. (2013). Exosomal and non-exosomal transport of extra-cellular microRNAs in follicular fluid: implications for bovine oocyte developmental competence. PLoS One 8, e78505.
| Exosomal and non-exosomal transport of extra-cellular microRNAs in follicular fluid: implications for bovine oocyte developmental competence.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhslGisLjJ&md5=48d1c73f7d3de8b6134d507fb2898365CAS |
Sontakke, S. D., Mohammed, B. T., McNeilly, A. S., and Donadeu, F. X. (2014). Characterization of microRNAs differentially expressed during bovine follicle development. Reproduction 148, 271–283.
| Characterization of microRNAs differentially expressed during bovine follicle development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhsVert7bP&md5=cd3307323a91325450880cabd7ac404fCAS | 24920665PubMed |
Wainwright, E. N., Jorgensen, J. S., Kim, Y., Truong, V., Bagheri-Fam, S., Davidson, T., Svingen, T., Fernandez-Valverde, S. L., McClelland, K. S., Taft, R. J., Harley, V. R., Koopman, P., and Wilhelm, D. (2013). SOX9 regulates microRNA miR-202-5p/3p expression during mouse testis differentiation. Biol. Reprod. 89, 34.
| SOX9 regulates microRNA miR-202-5p/3p expression during mouse testis differentiation.Crossref | GoogleScholarGoogle Scholar | 23843232PubMed |
Xu, S., Linher-Melville, K., Yang, B. B., Wu, D., and Li, J. (2011). Micro-RNA378 (miR-378) regulates ovarian estradiol production by targeting aromatase. Endocrinology 152, 3941–3951.
| Micro-RNA378 (miR-378) regulates ovarian estradiol production by targeting aromatase.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhsVanu77E&md5=a59b98758b16ed2619a872a1f7e1b245CAS | 21846797PubMed |
