Construction of a circRNA- lincRNA-lncRNA-miRNA-mRNA ceRNA regulatory network identifies genes and pathways linked to goat fertility.

Farzad Ghafouri, Mostafa Sadeghi, Abolfazl Bahrami, Masoumeh Naserkheil, Vahid Dehghanian Reyhan, Arash Javanmard, Seyed Reza Miraei-Ashtiani, Soheila Ghahremani, Herman W Barkema, Rostam Abdollahi-Arpanahi, John P Kastelic
Author Information
  1. Farzad Ghafouri: Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj, Iran.
  2. Mostafa Sadeghi: Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj, Iran.
  3. Abolfazl Bahrami: Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj, Iran.
  4. Masoumeh Naserkheil: Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj, Iran.
  5. Vahid Dehghanian Reyhan: Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj, Iran.
  6. Arash Javanmard: Department of Animal Sciences, Faculty of Agriculture, University of Tabriz, Tabriz, Iran.
  7. Seyed Reza Miraei-Ashtiani: Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj, Iran.
  8. Soheila Ghahremani: Department of Animal Science, Faculty of Agriculture, University of Tarbiat Modares, Tehran, Iran.
  9. Herman W Barkema: Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
  10. Rostam Abdollahi-Arpanahi: Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj, Iran.
  11. John P Kastelic: Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.

Abstract

There is growing interest in the genetic improvement of fertility traits in female goats. With high-throughput genotyping, single-cell RNA sequencing (scRNA-seq) is a powerful tool for measuring gene expression profiles. The primary objective was to investigate comparative transcriptome profiling of granulosa cells (GCs) of high- and low-fertility goats, using scRNA-seq. Thirty samples from Ji'ning Gray goats ( = 15 for high fertility and = 15 for low fertility) were retrieved from publicly available scRNA-seq data. Functional enrichment analysis and a literature mining approach were applied to explore modules and hub genes related to fertility. Then, interactions between types of RNAs identified were predicted, and the ceRNA regulatory network was constructed by integrating these interactions with other gene regulatory networks (GRNs). Comparative transcriptomics-related analyses identified 150 differentially expressed genes (DEGs) between high- and low-fertility groups, based on the fold change (≥5 and ≤-5) and false discovery rate (FDR <0.05). Among these genes, 80 were upregulated and 70 were downregulated. In addition, 81 mRNAs, 58 circRNAs, 8 lincRNAs, 19 lncRNAs, and 55 miRNAs were identified by literature mining. Furthermore, we identified 18 hub genes (, , , , , , , , , , , , , , , , , and ) involved in goat fertility. Identified biological networks and modules were mainly associated with ovary signature pathways. In addition, KEGG enrichment analysis identified regulating pluripotency of stem cells, cytokine-cytokine receptor interactions, ovarian steroidogenesis, oocyte meiosis, progesterone-mediated oocyte maturation, parathyroid and growth hormone synthesis, cortisol synthesis and secretion, and signaling pathways for prolactin, TGF-beta, Hippo, MAPK, PI3K-Akt, and FoxO. Functional annotation of identified DEGs implicated important biological pathways. These findings provided insights into the genetic basis of fertility in female goats and are an impetus to elucidate molecular ceRNA regulatory networks and functions of DEGs underlying ovarian follicular development.

Keywords

References

  1. Theranostics. 2020 Feb 10;10(7):3308-3324 [PMID: 32194870]
  2. Front Cell Dev Biol. 2022 Feb 03;10:820558 [PMID: 35186931]
  3. Bioinformatics. 2010 Jul 15;26(14):1783-5 [PMID: 20562416]
  4. Genome Res. 2003 Nov;13(11):2498-504 [PMID: 14597658]
  5. Zygote. 2011 Aug;19(3):205-14 [PMID: 21205389]
  6. J Reprod Dev. 2012;58(1):44-50 [PMID: 22450284]
  7. Front Cell Dev Biol. 2020 Feb 18;8:79 [PMID: 32133359]
  8. RNA Biol. 2016;13(1):34-42 [PMID: 26669964]
  9. Bioinformatics. 2008 Jan 15;24(2):282-4 [PMID: 18006545]
  10. Nucleic Acids Res. 2019 Jan 8;47(D1):D155-D162 [PMID: 30423142]
  11. Genet Mol Biol. 2011 Jan;34(1):49-55 [PMID: 21637543]
  12. Bioinformatics. 2014 Apr 1;30(7):923-30 [PMID: 24227677]
  13. Bioinformatics. 2013 May 15;29(10):1350-1 [PMID: 23595664]
  14. Gene. 2016 May 10;582(1):69-76 [PMID: 26851539]
  15. Vet Med Sci. 2020 May;6(2):187-195 [PMID: 31782269]
  16. Reprod Domest Anim. 2021 May;56(5):801-811 [PMID: 33624340]
  17. Anim Reprod Sci. 2011 Apr;124(3-4):211-9 [PMID: 20888155]
  18. Nat Rev Mol Cell Biol. 2007 Aug;8(8):613-21 [PMID: 17622252]
  19. Mol Cell. 2007 Jul 6;27(1):91-105 [PMID: 17612493]
  20. Mol Biol Rep. 2012 Sep;39(9):9167-77 [PMID: 22733487]
  21. Nat Protoc. 2009;4(1):44-57 [PMID: 19131956]
  22. Front Genet. 2021 Jun 25;12:648158 [PMID: 34249080]
  23. BMC Med Genomics. 2021 Mar 2;14(1):67 [PMID: 33653335]
  24. PeerJ. 2019 May 23;7:e6938 [PMID: 31198626]
  25. Biol Reprod. 2000 Apr;62(4):913-9 [PMID: 10727260]
  26. Mol Med Rep. 2018 Jan;17(1):699-704 [PMID: 29115550]
  27. Bioinformatics. 2014 Aug 1;30(15):2114-20 [PMID: 24695404]
  28. Genome Biol. 2014;15(12):550 [PMID: 25516281]
  29. Life Sci. 2015 Sep 1;136:28-35 [PMID: 26144623]
  30. Funct Integr Genomics. 2017 May;17(2-3):135-143 [PMID: 27681237]
  31. Reprod Nutr Dev. 2005 May-Jun;45(3):377-82 [PMID: 15982462]
  32. Nucleic Acids Res. 2006 Jan 1;34(Database issue):D504-6 [PMID: 16381921]
  33. Nucleic Acids Res. 2013 Jan;41(Database issue):D816-23 [PMID: 23203989]
  34. Mol Cells. 2019 Mar 31;42(3):189-199 [PMID: 30764602]
  35. Nucleic Acids Res. 2003 Jan 1;31(1):248-50 [PMID: 12519993]
  36. Anim Biotechnol. 2016;27(3):199-207 [PMID: 27135147]
  37. Heredity (Edinb). 2019 Feb;122(2):172-186 [PMID: 29784930]
  38. Biology (Basel). 2021 May 25;10(6): [PMID: 34070240]
  39. Mol Cancer. 2020 Dec 14;19(1):172 [PMID: 33317550]
  40. Med Sci Monit. 2019 Feb 12;25:1140-1154 [PMID: 30745559]
  41. OMICS. 2012 Jan-Feb;16(1-2):37-49 [PMID: 22321014]
  42. Nucleic Acids Res. 2019 Jan 8;47(D1):D135-D139 [PMID: 30371849]
  43. PLoS One. 2015 Mar 19;10(3):e0120170 [PMID: 25790350]
  44. Sci Rep. 2016 Dec 01;6:38096 [PMID: 27905513]
  45. Curr Issues Mol Biol. 2022 Jan 11;44(1):309-328 [PMID: 35723402]
  46. Cell. 2011 Aug 5;146(3):353-8 [PMID: 21802130]
  47. J Steroid Biochem Mol Biol. 2013 Nov;138:325-33 [PMID: 23816690]
  48. Nucleic Acids Res. 2019 Jan 8;47(D1):D607-D613 [PMID: 30476243]
  49. Genes (Basel). 2022 Jul 22;13(8): [PMID: 35893032]
  50. J Biol Res (Thessalon). 2019 May 06;26:3 [PMID: 31080783]
  51. Gene. 2018 Dec 30;679:297-304 [PMID: 30176317]
  52. Sci Rep. 2021 Aug 3;11(1):15698 [PMID: 34344973]
  53. Front Genet. 2020 Feb 18;10:1403 [PMID: 32133026]
  54. Bioinformatics. 2005 Mar;21(6):832-4 [PMID: 15531608]
  55. Reprod Domest Anim. 2013 Oct;48(5):803-9 [PMID: 23581245]
  56. Reproduction. 2017 Jul;154(1):51-65 [PMID: 28450315]
  57. Trends Pharmacol Sci. 1999 Oct;20(10):408-12 [PMID: 10577253]
  58. Gene. 2018 Feb 15;643:1-6 [PMID: 29208414]
  59. FASEB J. 2014 Aug;28(8):3396-410 [PMID: 24739304]
  60. Drug Discov Today. 2004 Feb 1;9(3):127-35 [PMID: 14960390]
  61. Nat Methods. 2015 Apr;12(4):357-60 [PMID: 25751142]
  62. Int J Genomics. 2020 Aug 18;2020:5940205 [PMID: 32904540]
  63. Nucleic Acids Res. 2016 Jul 8;44(W1):W83-9 [PMID: 27098042]
  64. PLoS One. 2018 Mar 28;13(3):e0194456 [PMID: 29590145]
  65. Reproduction. 2011 Dec;142(6):845-54 [PMID: 21930684]
  66. Animals (Basel). 2019 Oct 31;9(11): [PMID: 31683597]
  67. Front Genet. 2021 Jul 07;12:646297 [PMID: 34306005]
  68. Mol Cell Biol. 2008 Dec;28(23):7001-11 [PMID: 18809571]
  69. Sci Rep. 2016 Nov 29;6:37983 [PMID: 27897262]
  70. Cell Mol Life Sci. 2016 May;73(10):2079-87 [PMID: 26943803]
  71. Gene. 2013 Dec 10;532(1):140-5 [PMID: 24013084]
  72. Sci Rep. 2020 Apr 8;10(1):6050 [PMID: 32269277]
  73. Nat Methods. 2014 Feb;11(2):163-6 [PMID: 24363023]
  74. R Soc Open Sci. 2017 Dec 20;4(12):171415 [PMID: 29308264]

Word Cloud

Similar Articles

Cited By