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      The future of assessing bull fertility: Can the ‘omics fields identify usable biomarkers?

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          Abstract

          Breeding soundness examinations for bulls rely heavily on the subjective, visual assessment of sperm motility and morphology. Although these criteria have the potential to identify infertile males, they cannot be used to guarantee fertility or provide information about varying degrees of bull fertility. Male factor fertility is complex, and the success of the male gamete is not necessarily realized until well after the spermatozoon enters the oocyte. This paper reviews our existing knowledge of the bull’s contribution from a standpoint of the sperm’s cargo and the impact that this can have on fertilization and the development of the embryo. There has been a plethora of recent research characterizing the many molecular attributes that can affect the functional competence of a spermatozoon. A better understanding of the molecular factors influencing fertilization and embryo development in cattle will lead to the identification of biomarkers for the selection of bulls of superior fertility, which will have major implications for livestock production. To see this improvement in reproductive performance, we believe incorporation of modern technology into breeding soundness examinations will be necessary—although many of the discussed technologies are not ready for large-scale field application. Each of the ‘omics fields discussed in this review have shown promise for the identification of biomarkers of fertility, with certain families of biomarkers appearing to be better suited to different evaluations throughout a bull’s lifetime. Further research is needed for the proposed biomarkers to be of diagnostic or predictive value.

          Abstract

          A review of proteins, transcripts, and metabolites identified in spermatozoa and seminal plasma, with a focus on molecular factors correlated with high or low fertility bulls to evaluate if they could be used as predictive biomarkers in the future.

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          Most cited references123

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          Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder.

          Increasing evidence indicates that metabolic disorders in offspring can result from the father's diet, but the mechanism remains unclear. In a paternal mouse model given a high-fat diet (HFD), we showed that a subset of sperm transfer RNA-derived small RNAs (tsRNAs), mainly from 5' transfer RNA halves and ranging in size from 30 to 34 nucleotides, exhibited changes in expression profiles and RNA modifications. Injection of sperm tsRNA fractions from HFD males into normal zygotes generated metabolic disorders in the F1 offspring and altered gene expression of metabolic pathways in early embryos and islets of F1 offspring, which was unrelated to DNA methylation at CpG-enriched regions. Hence, sperm tsRNAs represent a paternal epigenetic factor that may mediate intergenerational inheritance of diet-induced metabolic disorders.
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            Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress.

            Epigenetic signatures in germ cells, capable of both responding to the parental environment and shaping offspring neurodevelopment, are uniquely positioned to mediate transgenerational outcomes. However, molecular mechanisms by which these marks may communicate experience-dependent information across generations are currently unknown. In our model of chronic paternal stress, we previously identified nine microRNAs (miRs) that were increased in the sperm of stressed sires and associated with reduced hypothalamic-pituitary-adrenal (HPA) stress axis reactivity in offspring. In the current study, we rigorously examine the hypothesis that these sperm miRs function postfertilization to alter offspring stress responsivity and, using zygote microinjection of the nine specific miRs, demonstrated a remarkable recapitulation of the offspring stress dysregulation phenotype. Further, we associated long-term reprogramming of the hypothalamic transcriptome with HPA axis dysfunction, noting a marked decreased in the expression of extracellular matrix and collagen gene sets that may reflect an underlying change in blood-brain barrier permeability. We conclude by investigating the developmental impact of sperm miRs in early zygotes with single-cell amplification technology, identifying the targeted degradation of stored maternal mRNA transcripts including sirtuin 1 and ubiquitin protein ligase E3a, two genes with established function in chromatin remodeling, and this potent regulatory function of miRs postfertilization likely initiates a cascade of molecular events that eventually alters stress reactivity. Overall, these findings demonstrate a clear mechanistic role for sperm miRs in the transgenerational transmission of paternal lifetime experiences.
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              The eukaryotic genome as an RNA machine.

              The past few years have revealed that the genomes of all studied eukaryotes are almost entirely transcribed, generating an enormous number of non-protein-coding RNAs (ncRNAs). In parallel, it is increasingly evident that many of these RNAs have regulatory functions. Here, we highlight recent advances that illustrate the diversity of ncRNA control of genome dynamics, cell biology, and developmental programming.
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                Author and article information

                Contributors
                Journal
                Biol Reprod
                Biol Reprod
                biolreprod
                Biology of Reproduction
                Oxford University Press
                0006-3363
                1529-7268
                May 2022
                07 February 2022
                07 February 2022
                : 106
                : 5
                : 854-864
                Affiliations
                Priority Research Centre for Reproductive Science, University of Newcastle , Callaghan, New South Wales, Australia
                Priority Research Centre for Reproductive Science, University of Newcastle , Callaghan, New South Wales, Australia
                Nuffield Department of Women’s and Reproductive Health, University of Oxford , Oxford, UK
                School of Animal and Veterinary Sciences, Charles Sturt University , Wagga Wagga, New South Wales, Australia
                Graham Centre for Agricultural Innovation, Charles Sturt University , Wagga Wagga, New South Wales, Australia
                School of Animal and Veterinary Sciences, Charles Sturt University , Wagga Wagga, New South Wales, Australia
                Graham Centre for Agricultural Innovation, Charles Sturt University , Wagga Wagga, New South Wales, Australia
                Priority Research Centre for Reproductive Science, University of Newcastle , Callaghan, New South Wales, Australia
                Priority Research Centre for Reproductive Science, University of Newcastle , Callaghan, New South Wales, Australia
                Author notes
                Correspondence: Priority Research Centre for Reproductive Science, University of Newcastle, University Drive, Callaghan, NSW 2308, Australia. E-mail: erin.klein@ 123456uon.edu.au
                Article
                ioac031
                10.1093/biolre/ioac031
                9113469
                35136971
                de0d2298-3c40-41e1-bcef-f734d61f4132
                © The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 23 August 2021
                : 27 January 2022
                : 31 January 2022
                : 21 March 2022
                Page count
                Pages: 11
                Funding
                Funded by: Meat & Livestock Australia Project;
                Award ID: B.GBP.0030
                Categories
                Review
                AcademicSubjects/MED00773
                AcademicSubjects/SCI01070

                bull fertility,sperm,seminal plasma,fertility marker,biomarker

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