Male fertility status is associated with DNA methylation signatures in sperm and transcriptomic profiles of bovine preimplantation embryos

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Abstract

Background

Infertility in dairy cattle is a concern where reduced fertilization rates and high embryonic loss are contributing factors. Studies of the paternal contribution to reproductive performance are limited. However, recent discoveries have shown that, in addition to DNA, sperm delivers transcription factors and epigenetic components that are required for fertilization and proper embryonic development. Hence, characterization of the paternal contribution at the time of fertilization is warranted. We hypothesized that sire fertility is associated with differences in DNA methylation patterns in sperm and that the embryonic transcriptomic profiles are influenced by the fertility status of the bull. Embryos were generated in vitro by fertilization with either a high or low fertility Holstein bull. Blastocysts derived from each high and low fertility bulls were evaluated for morphology, development, and transcriptomic analysis using RNA-Sequencing. Additionally, DNA methylation signatures of sperm from high and low fertility sires were characterized by performing whole-genome DNA methylation binding domain sequencing.

Results

Embryo morphology and developmental capacity did not differ between embryos generated from either a high or low fertility bull. However, RNA-Sequencing revealed 98 genes to be differentially expressed at a false discovery rate < 1%. A total of 65 genes were upregulated in high fertility bull derived embryos, and 33 genes were upregulated in low fertility derived embryos. Expression of the genes CYCS, EEA1, SLC16A7, MEPCE, and TFB2M was validated in three new pairs of biological replicates of embryos. The role of the differentially expressed gene TFB2M in embryonic development was further assessed through expression knockdown at the zygotic stage, which resulted in decreased development to the blastocyst stage. Assessment of the epigenetic signature of spermatozoa between high and low fertility bulls revealed 76 differentially methylated regions.

Conclusions

Despite similar morphology and development to the blastocyst stage, preimplantation embryos derived from high and low fertility bulls displayed significant transcriptomic differences. The relationship between the paternal contribution and the embryonic transcriptome is unclear, although differences in methylated regions were identified which could influence the reprogramming of the early embryo. Further characterization of paternal factors delivered to the oocyte could lead to the identification of biomarkers for better selection of sires to improve reproductive efficiency.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-017-3673-y) contains supplementary material, which is available to authorized users.

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Most cited references 57

Record: found
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Article: not found

Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade.

P. Li, D Nijhawan, I Budihardjo … (1997)

We report here the purification of the third protein factor, Apaf-3, that participates in caspase-3 activation in vitro. Apaf-3 was identified as a member of the caspase family, caspase-9. Caspase-9 and Apaf-1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome c and dATP, an event that leads to caspase-9 activation. Activated caspase-9 in turn cleaves and activates caspase-3. Depletion of caspase-9 from S-100 extracts diminished caspase-3 activation. Mutation of the active site of caspase-9 attenuated the activation of caspase-3 and cellular apoptotic response in vivo, indicating that caspase-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP.

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Reproductive loss in high-producing dairy cattle: where will it end?

M Lucy (2001)

The dairy industry in the United States has changed dramatically in the last decade. Milk production per cow has increased steadily because of a combination of improved management, better nutrition, and intense genetic selection. Dairy farms are larger, and nearly 30% of the dairy cows in the United States are on farms with 500 or more cows. The shift toward more productive cows and larger herds is associated with a decrease in reproductive efficiency. Cows with the greatest milk production have the highest incidence of infertility, but epidemiological studies suggest that, in addition to milk production, other factors are probably decreasing reproductive efficiency in our dairy herds. The reproductive physiology of dairy cows has changed over the past 50 yr, and physiological adaptations to high milk production may explain part of the reproductive decline. Critical areas for new research include control of the estrous cycle, metabolic effects of lactation on reproduction, mechanisms linking disease to reproduction, and early embryonic mortality. Solving reproductive loss in dairy cows will not be easy because only a small number of research groups study reproduction in postpartum dairy cows. Therefore, the present research base will need to be expanded. For this to occur, research funding must be increased above its current level and a renewed emphasis must be placed on solving the emerging crisis of infertility in dairy cows.

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Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides, unassisted by transfection reagents

C Stein, J. Hansen, Johnathan Lai … (2010)

For the past 15–20 years, the intracellular delivery and silencing activity of oligodeoxynucleotides have been essentially completely dependent on the use of a delivery technology (e.g. lipofection). We have developed a method (called ‘gymnosis’) that does not require the use of any transfection reagent or any additives to serum whatsoever, but rather takes advantage of the normal growth properties of cells in tissue culture in order to promote productive oligonucleotide uptake. This robust method permits the sequence-specific silencing of multiple targets in a large number of cell types in tissue culture, both at the protein and mRNA level, at concentrations in the low micromolar range. Optimum results were obtained with locked nucleic acid (LNA) phosphorothioate gap-mers. By appropriate manipulation of oligonucleotide dosing, this silencing can be continuously maintained with little or no toxicity for >240 days. High levels of oligonucleotide in the cell nucleus are not a requirement for gene silencing, contrary to long accepted dogma. In addition, gymnotic delivery can efficiently deliver oligonucleotides to suspension cells that are known to be very difficult to transfect. Finally, the pattern of gene silencing of in vitro gymnotically delivered oligonucleotides correlates particularly well with in vivo silencing. The establishment of this link is of particular significance to those in the academic research and drug discovery and development communities.

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Author and article information

Contributors

Hasan Khatib: (608) 263-3484 , hkhatib@wisc.edu

Journal

Journal ID (nlm-ta): BMC Genomics

Journal ID (iso-abbrev): BMC Genomics

Title: BMC Genomics

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2164

Publication date (Electronic): 5 April 2017

Publication date PMC-release: 5 April 2017

Publication date Collection: 2017

Volume: 18

Electronic Location Identifier: 280

Affiliations

[1 ]GRID grid.14003.36, Department of Animal Sciences, , University of Wisconsin-Madison, ; Madison, WI 53706 USA

[2 ]GRID grid.164295.d, Department of Animal and Avian Sciences, , University of Maryland, ; College Park, MD 20742 USA

[3 ]GRID grid.14003.36, Department of Obstetrics and Gynecology, , University of Wisconsin-Madison, ; Madison, WI 53792 USA

[4 ]GRID grid.268154.c, Present address: Department of Obstetrics and Gynecology, , West Virginia University, ; Morgantown, WV 26508 USA

Article

Publisher ID: 3673

DOI: 10.1186/s12864-017-3673-y

PMC ID: 5382486

PubMed ID: 28381255

SO-VID: b86b3274-d6de-4825-a02f-2d96815cb865

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 27 October 2016

Date accepted : 31 March 2017

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100007015, University of Wisconsin-Madison;

Award ID: MSN176063

Award ID: MSN162253

Award Recipient : Sana M. Salih Hasan Khatib

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ScienceOpen disciplines: Genetics

Keywords: fertility,embryonic development,methylation,transcriptome,ivf

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ScienceOpen disciplines: Genetics

Keywords: fertility, embryonic development, methylation, transcriptome, ivf

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Male fertility status is associated with DNA methylation signatures in sperm and transcriptomic profiles of bovine preimplantation embryos

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Abstract

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Role of Microbes in Soil Fertility and Human Health

Most cited references 57

Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade.

Reproductive loss in high-producing dairy cattle: where will it end?

Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides, unassisted by transfection reagents

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Cited by 47

Most referenced authors 1,229