Nutritional status affects the microRNA profile of the hypothalamus of female sheep
Heng Yang A , Shan Lin B , Xiaoping Lei A , Cong Yuan A , Yaosheng Yu A , Zongsheng Zhao A D and Jingbo Chen A C DA College of Animal Science and Technology, Shihezi University, North Fourth Road, Shihezi 832003, China.
B College of Life Sciences, Shihezi University, North Fourth Road, Shihezi 832003, China.
C Xinjiang Academy of Animal Sciences, Karamay Street No. 151, Urumqi 830000, China.
D Corresponding authors. Emails: zhaozongsh@shzu.edu.cn; chenjb126@126.com
Reproduction, Fertility and Development 30(7) 946-957 https://doi.org/10.1071/RD17179
Submitted: 19 August 2016 Accepted: 21 October 2017 Published: 25 January 2018
Abstract
Recent studies on the seasonal regulation of the oestrous cycle in sheep have focussed mainly on the responses to photoperiod. However, the brain systems that control reproductive activity also respond to nutritional inputs, although the molecular mechanisms involved are not completely understood. One possibility is that small, non-coding RNAs, such as micro-RNAs (miRNAs), have significant influence. In the present study, the amounts and characteristics of miRNAs in hypothalamus from oestrous and anestrous ewes, fed low- or high-nutrient diets, were compared using Illumina HiSeq sequencing technology. In total, 398 miRNAs, including 261 novel miRNAs, were identified in ewes with an enhanced nutritional status (HEN), whereas 384 miRNAs, including 247 novel miRNAs, were identified in the ewes with a lesser nutritional status (HAN). There were eight conserved and 140 novel miRNAs expressed differentially between the two libraries. Based on quantitative real-time polymerase chain reaction, six miRNAs were assessed to verify the accuracy of the library database. Moreover, the correlation between the miRNA target and several upstream and downstream genes in the oestrus-related pathways were also verified in hypothalamus nerve cells. According to the results, nutritional status plays an important role in oestrous regulation in sheep, and the hypothalamic processes and pathways induced by nutritional signals (folic acid and tyrosine) are different from those induced by photoperiodic regulation of oestrus. We have expanded the repertoire of sheep miRNAs that could contribute to the molecular mechanisms that regulate the initiation of oestrous cycles in anestrous ewes in response to the influence of nutritional status.
Additional keywords: miRNA, oestrus regulation, seasonal breeding.
References
Albring, A., Wendt, L., Harz, N., Englera, H., Wildeb, B., Witzkeb, O., and Schedlowski, M. (2014). Short-term treatment with the calcineurin inhibitor cyclosporine A decreases HPA axis activity and plasma noradrenaline levels in healthy male volunteers. Pharmacol. Biochem. Behav. 126, 73–76.| Short-term treatment with the calcineurin inhibitor cyclosporine A decreases HPA axis activity and plasma noradrenaline levels in healthy male volunteers.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhsFyns77O&md5=001b5594c6cbc705392c7d91fc570d11CAS |
Allen, D. M., and Lamming, G. E. (1961). Nutrition and reproduction in the ewe. J. Agric. Sci. 56, 69–79.
| Nutrition and reproduction in the ewe.Crossref | GoogleScholarGoogle Scholar |
Barrell, G. K., Thrun, L. A., Brown, M. E., Viguié, C., and Karsch, F. J. (2000). Importance of photoperiodic signal quality to entrainment of the circannual reproductive rhythm of the ewe 1. Biol. Reprod. 63, 769–774.
| Importance of photoperiodic signal quality to entrainment of the circannual reproductive rhythm of the ewe 1.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXmtFCiurg%3D&md5=acfa12280b1b80690ac8c2a25230e5b7CAS |
Bartel, D. P. (2004). MicroRNAs, genomics, biogenesis, mechanism, and function. Cell 116, 281–297.
| MicroRNAs, genomics, biogenesis, mechanism, and function.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhtVals7o%3D&md5=8b3adfe9324d9923df3ca30a123bba20CAS |
Benoit, C., Ould-Hamouda, H., Crepin, D., Gertler, A., and Amar, L. (2013). Early leptin blockade predisposes fat-fed rats to overweight and modifies hypothalamic microRNAs. J. Endocrinol. 218, 35–47.
| Early leptin blockade predisposes fat-fed rats to overweight and modifies hypothalamic microRNAs.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhtFWqtb3L&md5=2522cb4b7a5e6cd713c486da16e46163CAS |
Chen, A. Q., Wang, Z. G., Xu, Z. R., Yu, S. D., and Yang, Z. G. (2009). Analysis of gene expression in granulosa cells of ovine antral growing follicles using suppressive subtractive hybridization. Anim. Reprod. Sci. 115, 39–48.
| Analysis of gene expression in granulosa cells of ovine antral growing follicles using suppressive subtractive hybridization.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXptl2hsr0%3D&md5=093c50dc0578adad09a0e69386270f3cCAS |
Chen, L., Liu, K., Zhao, Z., Blair, H. T., and Zhang, P. (2012). Identification of sheep ovary genes potentially associated with off-season reproduction. J. Genet. Genomics 39, 181–190.
| Identification of sheep ovary genes potentially associated with off-season reproduction.Crossref | GoogleScholarGoogle Scholar |
Clarke, I. J. (2015). Hypothalamus as an endocrine organ. Compr. Physiol. 5, 217–253.
| Hypothalamus as an endocrine organ.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC2Mvms1Snsg%3D%3D&md5=e51215dcf53f284b60fd272ed429d462CAS |
Di, R., He, J. N., Song, S. H., Tian, D. M., Liu, Q. Y., Liang, X. J., Ma, Q., Sun, M., Wang, J. D., Zhao, W. M., Gao, J. L., Wang, J. X., Yang, Z. M., Ge, Y., and Chu, M. X. (2014). Characterization and comparative profiling of ovarian microRNAs during ovine anestrus and the breeding season. BMC Genomics 15, 899.
| Characterization and comparative profiling of ovarian microRNAs during ovine anestrus and the breeding season.Crossref | GoogleScholarGoogle Scholar |
Ebling, F. J. (2010). Photoperiodic regulation of puberty in seasonal species. Mol. Cell. Endocrinol. 324, 95–101.
| Photoperiodic regulation of puberty in seasonal species.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXotVWqsrg%3D&md5=08f3e74012eed52de8c6650da2f25b03CAS |
Forcada, F., and Abecia, J. A. (2006). The effect of nutrition on the seasonality of reproduction in ewes. Reprod. Nutr. Dev. 46, 355–365.
| The effect of nutrition on the seasonality of reproduction in ewes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtVOnsr3N&md5=611e9094997c5aea9e72d9a411377aefCAS |
Forcada, F., Abecia, J. A., and Sierra, I. (1992). Seasonal changes in oestrus activity and ovulation rate in Rasa Aragonesa ewes maintained at two different body condition levels. Small Rumin. Res. 8, 313–324.
| Seasonal changes in oestrus activity and ovulation rate in Rasa Aragonesa ewes maintained at two different body condition levels.Crossref | GoogleScholarGoogle Scholar |
Guan, Y., Liang, G., Hawken, P. A., Malecki, I. A., Cozens, G., Vercoe, P. E., Martin, G. B., and Guan, L. L. (2015). Roles of small RNAs in the effects of nutrition on apoptosis and spermatogenesis in the adult testis. Sci. Rep. 5, 10372.
| Roles of small RNAs in the effects of nutrition on apoptosis and spermatogenesis in the adult testis.Crossref | GoogleScholarGoogle Scholar |
Hunter, G. L. (1962). Observations on oestrus in Merinos. In ‘Proceedings of the South African Society of Animal Production 1, pp. 67–69.
Hurowitz, E. H., Melnyk, J. M., Chen, Y. J., Kouros-Mehr, H., Simon, M. I., and Shizuya, H. (2000). Genomic characterization of the human heterotrimeric G protein α, β, and γ subunit genes. DNA Res. 7, 111–120.
| Genomic characterization of the human heterotrimeric G protein α, β, and γ subunit genes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXjt1Glsbk%3D&md5=c2865596a43fec281f137e8e2f336a24CAS |
Hyun, S., Lee, J. H., Jin, H., Nam, J., and Namkoong, B. (2009). Conserved microRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K. Cell 139, 1096–1108.
| Conserved microRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhslartrw%3D&md5=c2502e06899f2ab8bf52fb2990167529CAS |
Johnston, R. J., Chang, S., Etchberger, J. F., Ortiz, C. O., and Hobert, O. (2005). MicroRNAs acting in a double-negative feedback loop to control a neuronal cell fate decision. Proc. Natl. Acad. Sci. USA 102, 12449–12454.
| MicroRNAs acting in a double-negative feedback loop to control a neuronal cell fate decision.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtVSjsr3L&md5=930af0c400501b2bc4682a1c9f28b31fCAS |
Kia, H. D., Chapdareh, W. M., Khani, A. H., Moghaddam, G., Rashidi, A., Sadri, H., and Alijani, S. (2012). Effects of flushing and hormonal treatment on reproductive performance of Iranian Markhoz goats. J. Anim. Physiol. Anim. Nutr. (Berl.) 96, 1157–1164.
| 1:CAS:528:DC%2BC3sXhsVWnu7o%3D&md5=4cb939e33caa4d950b46832e483226ccCAS |
Lachance, K., Barhdadi, A., Mongrain, I., Normand, V., Zakrzewski, M., Leblanc, M. H., Racine, N., Carrier, M., Ducharme, A., Turgeon, J., Dube, M. P., Phillips, M. S., White, M., and de Denus, S. (2012). PRKCB is associated with calcineurin inhibitor-induced renal dysfunction in heart transplant recipients. Pharmacogenet. Genomics 22, 336–343.
| 1:CAS:528:DC%2BC38XlsVarsro%3D&md5=7417b0036cf90e34b88ac9b82080d7feCAS |
Lazarin, G. B., Alves, N. G., Perez, J. R. O., Lima, R. R. D., Garcia, I. F. F., José Neto, A., Vale, D. N. C., and Saunders, G. D. A. (2012). Plasma urea nitrogen and progesterone concentrations and follicular dynamics in ewes fed proteins of different degradability. Rev. Bras. Zootec. 41, 1638–1647.
| Plasma urea nitrogen and progesterone concentrations and follicular dynamics in ewes fed proteins of different degradability.Crossref | GoogleScholarGoogle Scholar |
Martin, G. B., Rodger, J., and Blache, D. (2004). Nutritional and environmental effects on reproduction in small ruminants. Reprod. Fertil. Dev. 16, 491–501.
| Nutritional and environmental effects on reproduction in small ruminants.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD2cvht1WntA%3D%3D&md5=c8c90dd3902ea1a92a9880fdc87fe336CAS |
Meister, B., Herzer, S., and Silahtaroglu, A. (2013). MicroRNAs in the hypothalamus. Neuroendocrinology 98, 243–253.
| MicroRNAs in the hypothalamus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXksFygu7s%3D&md5=daafccf5bbadac1ae7402431f1115f81CAS |
Naguibneva, I., Ameyar-Zazoua, M., Polesskaya, A., Ait-Si-Ali, S., and Groisman, R. (2006). The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation. Nat. Cell Biol. 8, 278–284.
| The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhvVKhtLg%3D&md5=bb59c256573bc32a931176db1353fb4cCAS |
Nam, E. J., Yoon, H. J., Kim, S. W., Kim, H. G., and Kim, Y. T. (2008). MicroRNA expression profiles in serous ovarian carcinoma. Clin. Cancer Res. 14, 2690–2695.
| MicroRNA expression profiles in serous ovarian carcinoma.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXlsV2qtL8%3D&md5=437490408d644c9b28bdaf78bb62febdCAS |
National Institutes of Health (2011). ‘Guide for the Care and Use of Laboratory Animals (8th Ed.).’ (Public Health Service, National Institutes of Health: Bethesda.)
Quaresma, M., and Payan-Carreira, R. (2014). Influence of body condition score on triggering anestrus during non-breeding season on Asinina de Miranda donkeys. In ‘Reproduction in Domestic Animals. Vol. 49’. pp. 89–89. (Wiley-Blackwell: Hoboken, NJ, USA.)
Reinhart, B. J., Slack, F. J., Basson, M., Pasquinelli, A. E., and Bettinger, J. C. (2000). The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403, 901–906.
| The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXhs1Ors74%3D&md5=e884cca8109ae71ed3aaf6c49d74b22dCAS |
Rosa, H. J. D., and Bryant, M. J. (2003). Seasonality of reproduction in sheep. Small Rumin. Res. 48, 155–171.
| Seasonality of reproduction in sheep.Crossref | GoogleScholarGoogle Scholar |
Sangiao-Alvarellos, S., Manfredi-Lozano, M., Ruiz-Pino, F., Navarro, V. M., and Sanchez-Garrido, M. A. (2013). Changes in hypothalamic expression of the Lin28/let-7 system and related microRNAs during postnatal maturation and after experimental manipulations of puberty. Endocrinology 154, 942–955.
| Changes in hypothalamic expression of the Lin28/let-7 system and related microRNAs during postnatal maturation and after experimental manipulations of puberty.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXitVehtb0%3D&md5=0d09848443108b44c32cf431fb14f678CAS |
Schinckel, P. G. (1954). The effect of the presence of the ram on the ovarian activity of the ewe. Aust. J. Agric. Res. 5, 465–469.
| The effect of the presence of the ram on the ovarian activity of the ewe.Crossref | GoogleScholarGoogle Scholar |
Sisk, C. L., and Foster, D. L. (2004). The neural basis of puberty and adolescence. Nat. Neurosci. 7, 1040–1047.
| The neural basis of puberty and adolescence.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXnvVOnt78%3D&md5=0f5975f00ef5a1792ad0e7f824fde353CAS |
Smith, I. D. (1965). The influence of level of nutrition during winter and spring upon oestrous activity in the ewe. World Review of Animal Production 4, 95–102.
Smith, J. T., and Clarke, L. J. (2010). Seasonal breeding as a neuroendocrine model for puberty in sheep. Mol. Cell. Endocrinol. 324, 102–109.
| Seasonal breeding as a neuroendocrine model for puberty in sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXotVWru7w%3D&md5=030a90e833db9c8346a4a9064338e328CAS |
Somchit-Assavacheep, A. (2011). Influence of nutritional management on folliculogenesis in ewes. The Thai Journal of Veterinary Medicine 41, 25.
Wightman, B., Llho, H., and Ruvkun, G. (1993). Post-transcriptional regulation of the heterochronic gene lin-14 by W-4 mediates temporal pattern formation in C. elegans. Cell 75, 855–862.
| Post-transcriptional regulation of the heterochronic gene lin-14 by W-4 mediates temporal pattern formation in C. elegans.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2cXislyisA%3D%3D&md5=8496ba4dc14acc0f5751c85511e93cd4CAS |
Yang, Y., Ahn, Y. H., Chen, Y. L., Tan, X. C., Guo, L., Gibbons, D. L., Ungewiss, C., Peng, D. H., Liu, X., Lin, S. H., Thilaganathan, N., Wistuba, I. I., Rodriguez-Canales, J., McLendon, G., Creighton, C. J., and Kurie, J. M. (2014). ZEB1 sensitizes lung adenocarcinoma to metastasis suppression by PI3K antagonism. J. Clin. Invest. 124, 2696–2708.
| ZEB1 sensitizes lung adenocarcinoma to metastasis suppression by PI3K antagonism.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXpvFahs78%3D&md5=56d6478d48c3a7eca94b0d5d34409e72CAS |
Yang, H., Lin, S., Lei, X. P., Yuan, C., Tian, Z. W., Yu, Y. S., Zhao, Z. H., and Chen, J. B. (2016). Identification and profiling of microRNAs from ovary of estrous Kazakh sheep induced by nutritional status in the anestrous season. Anim. Reprod. Sci. 175, 18–26.
| Identification and profiling of microRNAs from ovary of estrous Kazakh sheep induced by nutritional status in the anestrous season.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28Xhslehu7%2FL&md5=c006487d3e132d6563c0a9dbcfcbe786CAS |
Zarazaga, L. A., Gatica, M. C., Celi, I., Guzmán, J. L., and Malpaux, B. (2011). Artificial long days and daily contact with bucks induce ovarian but not oestrous activity during the non-breeding season in Mediterranean goat females. Anim. Reprod. Sci. 125, 81–87.
| Artificial long days and daily contact with bucks induce ovarian but not oestrous activity during the non-breeding season in Mediterranean goat females.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC3Mrptlynsw%3D%3D&md5=4eebbd6cc832740c06231bf73930e3c7CAS |
Zhang, S., Blache, D., Blackberry, M. A., and Martin, G. B. (2004). Dynamics of the responses in secretion of luteinising hormone, leptin and insulin following an acute increase in nutrition in mature male sheep. Reprod. Fertil. Dev. 16, 823–829.
| Dynamics of the responses in secretion of luteinising hormone, leptin and insulin following an acute increase in nutrition in mature male sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXkt1WjsQ%3D%3D&md5=d5bb93a867088508e11282acc6266b8cCAS |