Animal Reproduction (AR)
Animal Reproduction (AR)

Identification of biomarkers for bull fertility using functional genomics

Muhammet Rasit Ugur; Denise D. Guerreiro; Arlindo A. Moura; Erdogan Memili

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Prediction of bull fertility is critical for the sustainability of both dairy and beef cattle production. Even though bulls produce ample amounts of sperm with normal parameters, some bulls may still suffer from subpar fertility. This causes major economic losses in the cattle industry because using artificial insemination, semen from one single bull can be used to inseminate hundreds of thousands of cows. Although there are several traditional methods to estimate bull fertility, such methods are not sufficient to explain and accurately predict the subfertility of individual bulls. Since fertility is a complex trait influenced by a number of factors including genetics, epigenetics, and environment, there is an urgent need for a comprehensive methodological approach to clarify uncertainty in male subfertility. The present review focuses on molecular and functional signatures of bull sperm associated with fertility. Potential roles of functional genomics (proteome, small noncoding RNAs, lipidome, metabolome) on determining male fertility and its potential as a fertility biomarker are discussed. This review provides a better understanding of the molecular signatures of viable and fertile sperm cells and their potential to be used as fertility biomarkers. This information will help uncover the underlying reasons for idiopathic subfertility.


bull sperm, bull fertility, fertility biomarkers, functional genomics


Abdollahi-Arpanahi R, Morota G, Peñagaricano F. Predicting bull fertility using genomic data and biological information. J Dairy Sci. 2017;100(12):9656-66. PMid:28987577.

Aitken RJ, Clarkson JS, Fishel S. Generation of reactive oxygen species, lipid peroxidation, and human sperm function. Biol Reprod. 1989;41(1):183-97. PMid:2553141.

Aitken RJ. Reactive oxygen species and human sperm function. In: Dale B, editor. Mechanism of fertilization: plants to humans. Berlin: Springer; 1990. p. 179-88.

Allfrey VG, Faulkner R, Mirsky AE. Acetylation and methylation of histones and their possible role in the regulation of rna synthesis. Proc Natl Acad Sci USA. 1964;51(5):786-94. PMid:14172992.

AlphaFold [homepage on the Internet]. 2022 [cited 2022 Feb 7]. Available from:

Alvarez JG, Storey BT. Spontaneous lipid peroxidation in rabbit epididymal spermatozoa: its effect on sperm motility. Biol Reprod. 1982;27(5):1102-8. PMid:6297627.

Alves MBR, Arruda RP, De Bem THC, Florez-Rodriguez SA, Sá MF Fo, Belleannée C, Meirelles FV, Silveira JC, Perecin F, Celeghini ECC. Sperm-borne miR-216b modulates cell proliferation during early embryo development via K-RAS. Sci Rep. 2019;9(1):1-14. PMid:31316130.

Amaral A, Castillo J, Estanyol JM, Luis Ballesca J, Ramalho-Santos J, Oliva R. Human sperm tail proteome suggests new endogenous metabolic pathways. Mol Cell Proteomics. 2013;12(2):330-42. PMid:23161514.

Andrews AJ, Luger K. Nucleosome structure(s) and stability: variations on a theme. Annu Rev Biophys. 2011;40(1):99-117. PMid:21332355.

Aoki VW, Liu L, Carrell DT. Identification and evaluation of a novel sperm protamine abnormality in a population of infertile males. Hum Reprod. 2005;20(5):1298-306. PMid:15705617.

Aoki VW, Liu L, Jones KP, Hatasaka HH, Gibson M, Peterson CM, Carrell DT. Sperm protamine 1/protamine 2 ratios are related to in vitro fertilization pregnancy rates and predictive of fertilization ability. Fertil Steril. 2006;86(5):1408-15. PMid:17011555.

Baker MA. Proteomics of post-translational modifications of mammalian spermatozoa. Cell Tissue Res. 2016;363(1):279-87. PMid:26239910.

Balhorn R. A model for the structure of chromatin in mammalian sperm. J Cell Biol. 1982;93(2):298-305. PMid:7096440.

Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21(3):381-95. PMid:21321607.

Bao J, Bedford MT. Epigenetic regulation of the histone-to-protamine transition during spermiogenesis. Reproduction. 2016;151(5):R55-70. PMid:26850883.

Batissaco L, Celeghini ECC, Pinaffi FLV, Oliveira BMM, Andrade AFC, Recalde ECS, Fernandes CB. Correlações entre a hemodinâmica testicular e as características espermáticas em carneiros. Braz J Vet Res Anim Sci. 2014;50(5):384-95.

Bellows DS, Ott SL, Bellows RA. Review: cost of reproductive diseases and conditions in cattle. Prof Anim Sci. 2002;18(1):26-32.

BioRender [homepage on the Internet]. 2022 [cited 2022 Feb 7]. Available from:

Bošković A, Torres-Padilla M-E. How mammals pack their sperm: a variant matter. Genes Dev. 2013;27(15):1635-9. PMid:23913918.

Braundmeier AG, Miller DJ. The search is on: finding accurate molecular markers of male fertility. J Dairy Sci. 2001;84(9):1915-25. PMid:11573769.

Brewer L, Corzett M, Lau EY, Balhorn R. Dynamics of protamine 1 binding to single DNA molecules. J Biol Chem. 2003;278(43):42403-8. PMid:12912999.

Butler ML, Bormann JM, Weaber RL, Grieger DM, Rolf MM. Selection for bull fertility: a review. Transl Anim Sci. 2019;4(1):423-41. PMid:32705001.

Byrne K, Leahy T, McCulloch R, Colgrave ML, Holland MK. Comprehensive mapping of the bull sperm surface proteome. Proteomics. 2012;12(23-24):3559-79. PMid:23081703.

Carvalho PD, Santos VG, Giordano JO, Wiltbank MC, Fricke PM. Development of fertility programs to achieve high 21-day pregnancy rates in high-producing dairy cows. Theriogenology. 2018;114:165-72. PMid:29627633.

Champroux A, Torres-Carreira J, Gharagozloo P, Drevet JR, Kocer A. Mammalian sperm nuclear organization: resiliencies and vulnerabilities. Basic Clin Androl. 2016;26(1):17. PMid:28031843.

Chenoweth PJ, Hopkins FM, Spitzer JC, Larsen RE. Guideline for using the bull breeding soundness evaluation form. theriogenology handbook. Clin Theriogenology. 2010;2(1):43-50.

Cho C, Jung-Ha H, Willis WD, Goulding EH, Stein P, Xu Z, Schultz RM, Hecht NB, Eddy EM. Protamine 2 deficiency leads to sperm DNA damage and embryo death in mice. Biol Reprod. 2003;69(1):211-7. PMid:12620939.

Codina M, Estanyol JM, Fidalgo MJ, Ballescà JL, Oliva R. Advances in sperm proteomics: best-practise methodology and clinical potential. Expert Rev Proteomics. 2015;12(3):255-77. PMid:25921224.

D’Amours O, Calvo É, Bourassa S, Vincent P, Blondin P, Sullivan R. Proteomic markers of low and high fertility bovine spermatozoa separated by Percoll gradient. Mol Reprod Dev. 2019;86(8):999-1012. PMid:31134708.

Dadoune JP, Siffroi JP, Alfonsi MF. Transcription in haploid male germ cells. Int Rev Cytol. 2004;237:1-56. PMid:15380665.

Dai P, Wang X, Gou LT, Li ZT, Wen Z, Chen ZG, Hua MM, Zhong A, Wang L, Su H, Wan H, Qian K, Liao L, Li J, Tian B, Li D, Fu XD, Shi HJ, Zhou Y, Liu MF. A translation-activating function of MIWI/piRNA during mouse spermiogenesis. Cell. 2019;179(7):1566-1581.e16. PMid:31835033.

Deepinder F, Chowdary HT, Agarwal A. Role of metabolomic analysis of biomarkers in the management of male infertility. Expert Rev Mol Diagn. 2007;7(4):351-8. PMid:17620044.

delBarco-Trillo J, Roldan ERS. Effects of metabolic rate and sperm competition on the fatty-acid composition of mammalian sperm. J Evol Biol. 2014;27(1):55-62. PMid:24251445.

delBarco-Trillo J, Tourmente M, Roldan ERS. Metabolic rate limits the effect of sperm competition on mammalian spermatogenesis. PLoS One. 2013;8(9):e76510. PMid:24069461.

Delbes G, Hales BF, Robaire B. Effects of the chemotherapy cocktail used to treat testicular cancer on sperm chromatin integrity. J Androl. 2007;28(2):241-9, discussion 250-1. PMid:17021337.

Dogan S, Vargovic P, Oliveira R, Belser LE, Kaya A, Moura A, Sutovsky P, Parrish J, Topper E, Memili E. Sperm protamine-status correlates to the fertility of breeding bulls. Biol Reprod. 2015;92(4):92. PMid:25673563.

Drabent B, Bode C, Miosge N, Herken R, Doenecke D. Expression of the mouse histone gene H1t begins at premeiotic stages of spermatogenesis. Cell Tissue Res. 1997;291(1):127-32. PMid:9394050.

Du Y, Wang X, Wang B, Chen W, He R, Zhang L, Xing X, Su J, Wang Y, Zhang Y. Deep sequencing analysis of microRNAs in bovine sperm. Mol Reprod Dev. 2014;81(11):1042-52. PMid:25279827.

Egea RR, Escrivá MM, Puchalt NG, Varghese AC. OMICS: current and future perspectives in reproductive medicine and technology. J Hum Reprod Sci. 2014;7(2):73-92. PMid:25191020.

Eirín-López JM, Frehlick LJ, Ausió J. Protamines, in the footsteps of linker histone evolution. J Biol Chem. 2006;281(1):1-4. PMid:16243843.

Erickson RP. Post-meiotic gene expression. Trends Genet. 1990;6(8):264-9. PMid:1978427.

Evans HC, Dinh TTN, Ugur MR, Hitit M, Sajeev D, Kaya A, Topper E, Nicodemus MC, Smith GD, Memili E. Lipidomic markers of sperm cryotolerance in cattle. Sci Rep. 2020;10(1):20192. PMid:33214639.

Fagerlind M, Stålhammar H, Olsson B, Klinga-Levan K. Expression of miRNAs in bull spermatozoa correlates with fertility rates. Reprod Domest Anim. 2015;50(4):587-94. PMid:25998690.

Fiehn O, Kopka J, Dörmann P, Altmann T, Trethewey RN, Willmitzer L. Metabolite profiling for plant functional genomics. Nat Biotechnol. 2000;18(11):1157-61. PMid:11062433.

Franken DR, Franken CJ, de la Guerre H, de Villiers A. Normal sperm morphology and chromatin packaging: comparison between aniline blue and chromomycin A3 staining. Andrologia. 1999;31(6):361-6. PMid:10643511.

Gacem S, Papas M, Catalan J, Miró J. Examination of jackass (Equus asinus) accessory sex glands by B‐mode ultrasound and of testicular artery blood flow by colour pulsed‐wave Doppler ultrasound: correlations with semen production. Reprod Domest Anim. 2020;55(2):181-8. PMid:31829461.

Gaviraghi A, Deriu F, Soggiu A, Galli A, Bonacina C, Bonizzi L, Roncada P. Proteomics to investigate fertility in bulls. Vet Res Commun. 2010;34(Suppl 1):33-6. PMid:20480233.

Giordano R, Magnano AR, Zaccagnini G, Pittoggi C, Moscufo N, Lorenzini R, Spadafora C. Reverse transcriptase activity in mature spermatoza of mouse. J Cell Biol. 2000;148(6):1107-13. PMid:10725323.

Gloria A, Carluccio A, Wegher L, Robbe D, Valorz C, Contri A. Pulse wave Doppler ultrasound of testicular arteries and their relationship with semen characteristics in healthy bulls. J Anim Sci Biotechnol. 2018;9(1):14. PMid:29441202.

Gomes F, Lemma B, Abeykoon D, Chen D, Wang Y, Fushman D, Fenselau C. Top-down analysis of novel synthetic branched proteins. J Mass Spectrom. 2019;54(1):19-25. PMid:30347468.

Govindaraju A, Uzun A, Robertson LS, Atli MO, Kaya A, Topper E, Crate EA, Padbury J, Perkins A, Memili E. Dynamics of microRNAs in bull spermatozoa. Reprod Biol Endocrinol. 2012;10(1):82. PMid:22978562.

Grunewald S, Paasch U, Glander HJ, Anderegg U. Mature human spermatozoa do not transcribe novel RNA. Andrologia. 2005;37(2-3):69-71. PMid:16026427.

Hammadeh ME, Hamad MF, Montenarh M, Fischer-Hammadeh C. Protamine contents and P1/P2 ratio in human spermatozoa from smokers and non-smokers. Hum Reprod. 2010;25(11):2708-20. PMid:20823111.

Hao S-L, Ni F-D, Yang W-X. The dynamics and regulation of chromatin remodeling during spermiogenesis. Gene. 2019;706:201-10. PMid:31085275.

Hazzouri M, Pivot-Pajot C, Faure AK, Usson Y, Pelletier R, Sèle B, Khochbin S, Rousseaux S. Regulated hyperacetylation of core histones during mouse spermatogenesis: involvement of histone-deacetylases. Eur J Cell Biol. 2000;79(12):950-60. PMid:11152286.

Hilz S, Modzelewski AJ, Cohen PE, Grimson A. The roles of microRNAs and siRNAs in mammalian spermatogenesis. Development. 2016;143(17):3061-73. PMid:27578177.

Holt WV, van Look KJW. Concepts in sperm heterogeneity, sperm selection and sperm competition as biological foundations for laboratory tests of semen quality. Reproduction. 2004;127(5):527-35. PMid:15129008.

Hopper RM, King EH. Bovine reproduction. Hoboken: John Wiley & Sons; 2014. Evaluation of breeding soundness; p. 68-78.

Hopper RM. Bovine reproduction. Hoboken: John Wiley & Sons; 2014. Breeding soundness examination in the bull: concepts and historical perspective; p. 58-63.

Hossain MS, Tareq KMA, Hammano KI, Tsujii H. Effect of fatty acids on boar sperm motility, viability and acrosome reaction. Reprod Med Biol. 2007;6(4):235-9. PMid:29699281.

Hud NV, Allen MJ, Downing KH, Lee J, Balhorn R. Identification of the elemental packing unit of DNA in mammalian sperm cells by atomic force microscopy. Biochem Biophys Res Commun. 1993;193(3):1347-54. PMid:8323555.

Hulbert AJ, Kelly MA, Abbott SK. Polyunsaturated fats, membrane lipids and animal longevity. J Comp Physiol B. 2014;184(2):149-66. PMid:24129945.

Islam MM, Umehara T, Tsujita N, Shimada M. Saturated fatty acids accelerate linear motility through mitochondrial ATP production in bull sperm. Reprod Med Biol. 2021;20(3):289-98. PMid:34262396.

Janiszewska E, Kratz EM. Could the glycosylation analysis of seminal plasma clusterin become a novel male infertility biomarker? Mol Reprod Dev. 2020;87(5):515-24. PMid:32222009.

Kastelic JP. Male involvement in fertility and factors affecting semen quality in bulls. Anim Front. 2013;3(4):20-5.

Kaya A, Dogan S, Vargovic P, Kutchy NA, Ross P, Topper E, Oko R, van der Hoorn F, Sutovsky P, Memili E. Sperm proteins ODF2 and PAWP as markers of fertility in breeding bulls. Cell Tissue Res. 2022;387(1):159-71. PMid:34762184.

Kazerooni T, Asadi N, Jadid L, Kazerooni M, Ghanadi A, Ghaffarpasand F, Kazerooni Y, Zolghadr J. Evaluation of sperm’s chromatin quality with acridine orange test, chromomycin A3 and aniline blue staining in couples with unexplained recurrent abortion. J Assist Reprod Genet. 2009;26(11-12):591-6. PMid:19894107.

Kenny DA, Byrne CJ. Review: the effect of nutrition on timing of pubertal onset and subsequent fertility in the bull. Animal. 2018;12(s1):s36-44. PMid:29554994.

Klose C, Surma MA, Simons K. Organellar lipidomics: background and perspectives. Curr Opin Cell Biol. 2013;25(4):406-13. PMid:23608594.

Kumar A, Kroetsch T, Blondin P, Anzar M. Fertility-associated metabolites in bull seminal plasma and blood serum: 1H nuclear magnetic resonance analysis. Mol Reprod Dev. 2015;82(2):123-31. PMid:25640164.

Kutchy NA, Menezes ESB, Chiappetta A, Tan W, Wills RW, Kaya A, Topper E, Moura AA, Perkins AD, Memili E. Acetylation and methylation of sperm histone 3 lysine 27 (H3K27ac and H3K27me3) are associated with bull fertility. Andrologia. 2018;50(3):1-11. PMid:29057498.

Kutchy NA, Velho A, Menezes ESB, Jacobsen M, Thibaudeau G, Wills RW, Moura A, Kaya A, Perkins A, Memili E. Testis specific histone 2B is associated with sperm chromatin dynamics and bull fertility: a pilot study. Reprod Biol Endocrinol. 2017;15(1):59. PMid:28764714.

Laxmivandana R, Patole C, Sharma TR, Sharma KK, Naskar S. Differential proteins associated with plasma membrane in X- and/or Y-chromosome bearing spermatozoa in indicus cattle. Reprod Domest Anim. 2021;56(6):928-35. PMid:33829570.

Lemos H, Dorado J, Hidalgo M, Gaivão I, Martins-Bessa A. Assessment of dog testis perfusion by colour and pulsed-doppler ultrasonography and correlation with sperm oxidative DNA damage. Top Companion Anim Med. 2020;41:100452. PMid:32823153.

Lenzi A, Picardo M, Gandini L, Dondero F. Lipids of the sperm plasma membrane: from polyunsaturated fatty acids considered as markers of sperm function to possible scavenger therapy. Hum Reprod Update. 1996;2(3):246-56. PMid:9079417.

Liang J, Zheng Y, Zeng W, Chen L, Yang S, Du P, Wang Y, Yu X, Zhang X. Proteomic profile of sperm in infertile males reveals changes in metabolic pathways. Protein J. 2021;1(6):1-11. PMid:34213690.

Longobardi V, Kosior MA, Pagano N, Fatone G, Staropoli A, Vassetti A, Vinale F, Campanile G, Gasparrini B. Changes in bull semen metabolome in relation to cryopreservation and fertility. Animals. 2020;10(6):929. PMid:32575657.

Maeshima K, Hihara S, Eltsov M. Chromatin structure: does the 30-nm fibre exist in vivo? Curr Opin Cell Biol. 2010;22(3):291-7. PMid:20346642.

Memili E, Dogan S, Rodriguez-Osorio N, Wang X, Oliveira RV, Mason MC, Govindaraju A, Grant KE, Belser LE, Crate E, Moura A, Kaya A. Makings of the best spermatozoa: molecular determinants of high fertility. In: Bashamboo A, editor. Male infertility. London: InTech; 2012.

Menezes EB, Velho ALC, Santos F, Dinh T, Kaya A, Topper E, Moura AA, Memili E. Uncovering sperm metabolome to discover biomarkers for bull fertility. BMC Genomics. 2019;20(1):714. PMid:31533629.

Mengual L, Ballescá JL, Ascaso C, Oliva R. Marked differences in protamine content and P1/P2 ratios in sperm cells from percoll fractions between patients and controls. J Androl. 2003;24(3):438-47. PMid:12721220.

Miller D, Briggs D, Snowden H, Hamlington J, Rollinson S, Lilford R, Krawetz SA. A complex population of RNAs exists in human ejaculate spermatozoa: implications for understanding molecular aspects of spermiogenesis. Gene. 1999;237(2):385-92. PMid:10521662.

Miller D, Ostermeier GC. Towards a better understanding of RNA carriage by ejaculate spermatozoa. Hum Reprod Update. 2006;12(6):757-67. PMid:16882702.

Moorey SE, Biase FH. Beef heifer fertility: importance of management practices and technological advancements. J Anim Sci Biotechnol. 2020;11(1):97. PMid:33014361.

Mostek A, Janta A, Ciereszko A. Proteomic comparison of non-sexed and sexed (X-bearing) cryopreserved bull semen. Anim Reprod Sci. 2020;221:106552. PMid:32861114.

Muro E, Atilla-Gokcumen GE, Eggert US. Lipids in cell biology: how can we understand them better? Mol Biol Cell. 2014;25(12):1819-23. PMid:24925915.

Nasr-Esfahani MH, Razavi S, Mozdarani H, Mardani M, Azvagi H. Relationship between protamine deficiency with fertilization rate and incidence of sperm premature chromosomal condensation post-ICSI. Andrologia. 2004;36(3):95-100. PMid:15206907.

Nigam PS, Singh A. Fermentation (industrial): production of oils and fatty acids. In: Batt CA, Tortorello ML, editors. Encyclopedia of food microbiology. 2nd ed. Amsterdam: Academic Press; 2014. p. 792-803.

O’Brien J, Hayder H, Zayed Y, Peng C. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol. 2018;9:402. PMid:30123182.

Oliva R, Bazett-Jones D, Mezquita C, Dixon GH. Factors affecting nucleosome disassembly by protamines in vitro. Histone hyperacetylation and chromatin structure, time dependence, and the size of the sperm nuclear proteins. J Biol Chem. 1987;262(35):17016-25. PMid:3680288.

Oliva R, Mezquita C. Marked differences in the ability of distinct protamines to disassemble nucleosomal core particles in vitro. Biochemistry. 1986;25(21):6508-11. PMid:3790536.

Oliveira RV, Dogan S, Belser LE, Kaya A, Topper E, Moura A, Thibaudeau G, Memili E. Molecular morphology and function of bull spermatozoa linked to histones and associated with fertility. Reproduction. 2013;146(3):263-72. PMid:23904564.

Ortiz-Rodriguez JM, Anel-Lopez L, Martin-Munõz P, Lvarez M, Gaitskell-Phillips G, Anel L, Rodriguez-Medina P, Penã FJ, Ortega-Ferrusola C. Pulse Doppler ultrasound as a tool for the diagnosis of chronic testicular dysfunction in stallions. PLoS One. 2017;12(5):e0175878. PMid:28558006.

Parisi AM, Thompson SK, Kaya A, Memili E. Molecular, cellular, and physiological determinants of bull fertility. Turk J Vet Anim Sci. 2014;38(6):637-42.

Peddinti D, Nanduri B, Kaya A, Feugang JM, Burgess SC, Memili E. Comprehensive proteomic analysis of bovine spermatozoa of varying fertility rates and identification of biomarkers associated with fertility. BMC Syst Biol. 2008;2(1):1-14. PMid:18294385.

Polo SE, Jackson SP. Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications. Genes Dev. 2011;25(5):409-33. PMid:21363960.

Powers R, Riekeberg E. New frontiers in metabolomics: from measurement to insight. F1000 Res. 2017;6:1148. PMid:28781759.

Ramesha KP, Mol P, Kannegundla U, Thota LN, Gopalakrishnan L, Rana E, Azharuddin N, Mangalaparthi KK, Kumar M, Dey G, Patil A, Saravanan K, Behera SK, Jeyakumar S, Kumaresan A, Kataktalware MA, Prasad TSK. Deep proteome profiling of semen of indian indigenous Malnad Gidda (Bos indicus) Cattle. J Proteome Res. 2020;19(8):3364-76. PMid:32508098.

Rathke C, Baarends WM, Awe S, Renkawitz-Pohl R. Chromatin dynamics during spermiogenesis. Biochim Biophys Acta. 2014;1839(3):155-68. PMid:24091090.

Rego JPA, Crisp JM, Moura AA, Nouwens AS, Li Y, Venus B, Corbet NJ, Corbet DH, Burns BM, Boe-Hansen GB, McGowan MR. Seminal plasma proteome of electroejaculated Bos indicus bulls. Anim Reprod Sci. 2014;148(1-2):1-17. PMid:24889044.

Rego JPA, Martins JM, Wolf CA, van Tilburg M, Moreno F, Monteiro-Moreira AC, Moreira RA, Santos DO, Moura AA. Proteomic analysis of seminal plasma and sperm cells and their associations with semen freezability in Guzerat bulls. J Anim Sci. 2016;94(12):5308-20. PMid:28046165.

Reichow SL, Hamma T, Ferré-D’Amaré AR, Varani G. The structure and function of small nucleolar ribonucleoproteins. Nucleic Acids Res. 2007;35(5):1452-64. PMid:17284456.

Reilly JN, McLaughlin EA, Stanger SJ, Anderson AL, Hutcheon K, Church K, Mihalas BP, Tyagi S, Holt JE, Eamens AL, Nixon B. Characterisation of mouse epididymosomes reveals a complex profile of microRNAs and a potential mechanism for modification of the sperm epigenome. Sci Rep. 2016;6(1):31794. PMid:27549865.

Ren X, Chen X, Wang Z, Wang D. Is transcription in sperm stationary or dynamic? J Reprod Dev. 2017;63(5):439-43. PMid:28845020.

Richmond TJ, Davey CA. The structure of DNA in the nucleosome core. Nature. 2003;423(6936):145-50. PMid:12736678.

Rivera-Egea R, Garrido N, Sota N, Meseguer M, Remohí J, Dominguez F. Sperm lipidic profiles differ significantly between ejaculates resulting in pregnancy or not following intracytoplasmic sperm injection. J Assist Reprod Genet. 2018;35(11):1973-85. PMid:30105539.

Santos AL, Preta G. Lipids in the cell: organisation regulates function. Cell Mol Life Sci. 2018;75(11):1909-27. PMid:29427074.

Selvaraju S, Parthipan S, Somashekar L, Binsila BK, Kolte AP, Arangasamy A, Ravindra JP, Krawetz SA. Current status of sperm functional genomics and its diagnostic potential of fertility in bovine (Bos taurus). Syst Biol Reprod Med. 2018a;64(6):484-501. PMid:29537884.

Selvaraju S, Parthipan S, Somashekar L, Binsila BK, Kolte AP, Arangasamy A, Ravindra JP, Krawetz SA. Current status of sperm functional genomics and its diagnostic potential of fertility in bovine (Bos taurus). Syst Biol Reprod Med. 2018b;64(6):484-501. PMid:29537884.

Simon L, Castillo J, Oliva R, Lewis SEM. Relationships between human sperm protamines, DNA damage and assisted reproduction outcomes. Reprod Biomed Online. 2011;23(6):724-34. PMid:22036908.

Singh BP, Sankhala RS, Asthana A, Ramakrishna T, Rao CM, Swamy MJ. Glycosylation differentially modulates membranolytic and chaperone-like activities of PDC-109, the major protein of bovine seminal plasma. Biochem Biophys Res Commun. 2019;511(1):28-34. PMid:30765224.

Soler-Ventura A, Gay M, Jodar M, Vilanova M, Castillo J, Arauz-Garofalo G, Villarreal L, Ballescà JL, Vilaseca M, Oliva R. Characterization of human sperm protamine proteoforms through a combination of top-down and bottom-up mass spectrometry approaches. J Proteome Res. 2020;19(1):221-37. PMid:31703166.

Spencer VA, Davie JR. Role of covalent modifications of histones in regulating gene expression. Gene. 1999;240(1):1-12. PMid:10564807.

Talbert PB, Henikoff S. Histone variants: ancient wrap artists of the epigenome. Nat Rev Mol Cell Biol. 2010;11(4):264-75. PMid:20197778.

Tang MCW, Jacobs SA, Mattiske DM, Soh YM, Graham AN, Tran A, Lim SL, Hudson DF, Kalitsis P, O’Bryan MK, Wong LH, Mann JR. Contribution of the two genes encoding histone variant H3.3 to viability and fertility in mice. PLoS Genet. 2015;11(2):e1004964. PMid:25675407.

Toby TK, Fornelli L, Kelleher NL. Progress in top-down proteomics and the analysis of proteoforms. Annu Rev Anal Chem. 2016;9(1):499-519. PMid:27306313.

Tourmente M, Gomendio M, Roldan ERS. Mass-specific metabolic rate and sperm competition determine sperm size in marsupial mammals. PLoS One. 2011;6(6):e21244. PMid:21731682.

Ugur MR, Dinh T, Hitit M, Kaya A, Topper E, Didion B, Memili E. Amino acids of seminal plasma associated with freezability of bull sperm. Front Cell Dev Biol. 2020;7:347. PMid:31993417.

Ugur MR, Kutchy NA, de Menezes EB, Ul-Husna A, Haynes BP, Uzun A, Kaya A, Topper E, Moura A, Memili E. Retained acetylated histone four in bull sperm associated with fertility. Front Vet Sci. 2019;6:223. PMid:31417913.

United Nations. Department of Economic and Social Affairs – DESA. Population division. New York: DESA; 2017.

United States Department of Agriculture – USDA. Beef 2007-08. Part IV: reference of beef cow-calf management practices in the United States, 2007-2008. Washington DC; 2010.

United States Department of Agriculture - USDA. Dairy 2014, “Health and Management Practices on U.S. Dairy Operations, 2014” USDA–APHIS–VS–CEAH–NAHMS. Fort Collins, CO #696.0218. Washington DC; 2018.

van Tilburg M, Sousa S, Lobo MDP, Monteiro-Azevedo ACOM, Azevedo RA, Araújo AA, Moura AA. Mapping the major proteome of reproductive fluids and sperm membranes of rams: from the cauda epididymis to ejaculation. Theriogenology. 2021;159:98-107. PMid:33126182.

Velasco A, Ruiz S. New approaches to assess fertility in domestic animals: relationship between arterial blood flow to the testicles and seminal quality. Animals. 2020;11(1):12. PMid:33374860.

Velho ALC, Menezes E, Dinh T, Kaya A, Topper E, Moura AA, Memili E. Metabolomic markers of fertility in bull seminal plasma. PLoS One. 2018;13(4):e0195279. PMid:29634739.

Viana AGA, Ribeiro IM, Carvalho RPR, Memili E, Moura AA, Machado-Neves M. Functional attributes of seminal proteins in bull fertility: a systematic review. Reproduction. 2021;161(4):459-75. PMid:33606662.

Vibranovski MD, Chalopin DS, Lopes HF, Long M, Karr TL. Direct evidence for postmeiotic transcription during drosophila melanogaster spermatogenesis. Genetics. 2010;186(1):431-3. PMid:20610406.

Walsh CT, Garneau-Tsodikova S, Gatto GJ Jr. Protein posttranslational modifications: the chemistry of proteome diversifications. Angew Chem Int Ed Engl. 2005;44(45):7342-72. PMid:16267872.

Wang M, Liu X, Chang G, Chen Y, An G, Yan L, Gao S, Xu Y, Cui Y, Dong J, Chen Y, Fan X, Hu Y, Song K, Zhu X, Gao Y, Yao Z, Bian S, Hou Y, Lu J, Wang R, Fan Y, Lian Y, Tang W, Wang Y, Liu J, Zhao L, Wang L, Liu Z, Yuan R, Shi Y, Hu B, Ren X, Tang F, Zhao XY, Qiao J. Single-cell RNA sequencing analysis reveals sequential cell fate transition during human spermatogenesis. Cell Stem Cell. 2018;23(4):599-614.e4. PMid:30174296.

Ward WS. Function of sperm chromatin structural elements in fertilization and development. Mol Hum Reprod. 2010;16(1):30-6. PMid:19748904.

Watson CN, Belli A, Di Pietro V. Small non-coding RNAs: new class of biomarkers and potential therapeutic targets in neurodegenerative disease. Front Genet. 2019;10:364. PMid:31080456.

Westfalewicz B, Słowińska M, Judycka S, Ciereszko A, Dietrich MA. Comparative proteomic analysis of young and adult bull (Bos taurus) cryopreserved semen. Animals. 2021;11(7):2013. PMid:34359141.

Wright MW, Bruford EA. Naming “junk”: human non-protein coding RNA (ncRNA) gene nomenclature. Hum Genomics. 2011;5(2):90-8. PMid:21296742.

Wymann MP, Schneiter R. Lipid signalling in disease. Nat Rev Mol Cell Biol. 2008;9(2):162-76. PMid:18216772.

Yuan S, Schuster A, Tang C, Yu T, Ortogero N, Bao J, Zheng H, Yan W. Sperm-borne miRNAs and endo-siRNAs are important for fertilization and preimplantation embryonic development. Development. 2016;143(4):635-47. PMid:26718009.

Zhang C, Gao L, Xu EY. LncRNA, a new component of expanding RNA-protein regulatory network important for animal sperm development. Semin Cell Dev Biol. 2016;59:110-7. PMid:27345292.

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