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Epigenetics of bull spermatozoa: a special case

When compared with the sperm of other mammals, bull spermatozoa genome is undermethylated (45.5% versus 57.1% to 76.1% for the other species).

By Sylvie André
Updated on 09/21/2018
Published on 09/19/2018


Spermatozoa have a remarkable epigenome in line with their degree of specialization, their unique nature and different requirements for successful fertilization. Accordingly, perturbations in the establishment of DNA methylation patterns during male germ cell differentiation have been associated with infertility in several species.

While bull semen is widely used in artificial insemination, the literature describing DNA methylation in bull spermatozoa is still scarce. The purpose of this study was therefore to characterize the bull sperm methylome relative to both bovine somatic cells and the sperm of other mammals through a multiscale analysis.


The quantification of DNA methylation at CCGG sites using luminometric methylation assay (LUMA) highlighted the undermethylation of bull sperm compared to the sperm of rams, stallions, mice, goats and men.

Total blood cells displayed a similarly high level of methylation in bulls and rams, suggesting that undermethylation of the bovine genome was specific to sperm. Annotation of CCGG sites in different species revealed no striking bias in the distribution of genome features targeted by LUMA that could explain undermethylation of bull sperm. To map DNA methylation at a genome-wide scale, bull sperm was compared with bovine liver, fibroblasts and monocytes using reduced representation bisulfite sequencing (RRBS) and immunoprecipitation of methylated DNA followed by microarray hybridization (MeDIP-chip). These two methods exhibited differences in terms of genome coverage, and consistently, two independent sets of sequences differentially methylated in sperm and somatic cells were identified for RRBS and MeDIP-chip. Remarkably, in the two sets most of the differentially methylated sequences were hypomethylated in sperm. In agreement with previous studies in other species, the sequences that were specifically hypomethylated in bull sperm targeted processes  relevant to the germline differentiation program (piRNA metabolism, meiosis, spermatogenesis) and sperm functions (cell adhesion, fertilization), as well as satellites and rDNA repeats.


These results highlight the undermethylation of bull spermatozoa when compared with both bovine somatic cells and the sperm of other mammals, and raise questions regarding the dynamics of DNA methylation in bovine male germline. Whether sperm undermethylation has potential interactions with structural variation in the cattle genome may deserve further attention.

Scientific contact(s):

Associated Division(s):
Animal Physiology and Livestock Systems
Associated Centre(s):


ANR-13-LAB3-0008-01, LabCom « SeQuaMol » and ANR-11-INBS-0003, « CRB-Anim »


Article from this study:

1. Perrier JP, Sellem E, Prezelin A, Gasselin M, Jouneau L, Piumi F, Al Adhami H, Weber M, Fritz S, Boichard D, Le Danvic C, Schibler L, Jammes H, Kiefer H: A multi-scale analysis of bull sperm methylome revealed both species peculiarities and conserved tissue-specific features. BMC Genomics 2018,19(1):404.

other articles cited:

2. Qu J, Hodges E, Molaro A, Gagneux P, Dean MD, Hannon GJ, Smith AD: Evolutionary expansion of DNA hypomethylation in the mammalian germline genome. Genome Research 2018,28(2):145-158.

3. Tang WW, Kobayashi T, Irie N, Dietmann S, Surani MA: Specification and epigenetic programming of the human germ line. Nature Reviews Genetics 2016,17(10):585-600.