Failures to maintain CpG-methylation of CoRSIVs in bovine sperm are associated with low sire conception.

In brief: Correlated regions of systemic interindividual epigenetic variation (CoRSIVs) are genomic regions with CpG-methylation patterns that differ between individuals, yet are consistent between tissues, within the same individual. Analyzing two groups of Holstein bull methylomes-nine with a high sire-conception rate (SCR) and nine with a low SCR-we found that a common type of CoRSIVs was significantly associated with reduced SCR and is thus suggested as a biomarker for SCR because it was highly methylated in sperm, but failed to retain hypermethylation in the gametes of males with low SCR. Abstract: Correlated regions of systemic interindividual epigenetic variation (CoRSIVs) are genomic regions with CpG-methylation patterns that differ between individuals, yet are consistent between tissues, within the same individual; therefore, their methylation can be profiled in bodily fluids that are easily obtained, such as blood and semen. Bearing in mind the simple epigenetic profiling of CoRSIVs, we tested whether this type of differentially methylated region (DMR) is associated with bovine fertility. Sequence Read Archive (SRA) meth BLAST was used to estimate CoRSIVs methylation status in 18 healthy, representative, and age-matched Holstein bulls, among which nine had high (H) sire-conception rate (SCR), and the other nine had low (L) SCR (group averages of SCR: 3.3 ± 0.6 and -3.8 ± 1.8, respectively). This method was also applied to morula and trophoblast SRA methylomes. Analysis with meth BLAST was effective for most (80%) CoRSIVs and showed that CoRSIVs are reprogrammed during blastocyst formation, although this method was incapable of specifically determining the methylation level in CoRSIVs with retrotransposons. In sperm, the effect of global methylation was evident in a common (25%) type of CoRSIVs that is highly (94.5% ± 4.3%) methylated in sperm. Specifically, a failure to retain hypermethylation in the sperm plus strand was significantly (p < 0.00025) indicative of low SCR. Comparing global DNA methylation using the latter type of CoRSIVs between sperm and blood can be used as a better biomarker for fertility than using other differentially methylated regions with more complex epigenetics.