Epigenetic clock and methylation study of oocytes from a bovine model of reproductive aging

Abstract

Cattle are an attractive animal model of fertility in women due to their high degree of similarity relative to follicle selection, embryo cleavage, blastocyst formation, and gestation length. To facilitate future studies of the epigenetic underpinnings of aging effects in the female reproductive axis, several DNA methylation-based biomarkers of aging (epigenetic clocks) for bovine oocytes are presented. One such clock was germane to only oocytes, while a dual-tissue clock was highly predictive of age in both oocytes and blood. Dual species clocks that apply to both humans and cattle were also developed and evaluated. These epigenetic clocks can be used to accurately estimate the chronological age of the oocyte donor. Both epigenetic clock studies and epigenome wide association studies revealed that blood and oocytes differ substantially with respect aging and the underlying epigenetic signatures that potentially influence the aging process. The rate of epigenetic aging was found to be slower in oocytes compared to blood, however, oocytes appeared to begin at an older epigenetic age. The epigenetic clocks for oocytes are expected to address questions in the field of reproductive aging, including the central question: how to slow aging of oocytes.

A mammalian methylation array for profiling methylation levels at conserved sequences

“…sequencing-based data, we used mammalian methylation array data from blood samples of horses 32 and cattle 33 to calculate mean methylation levels for each CpG in the respective species. Next, these mean values in blood were correlated to corresponding mean values from reduced representation bisulfite sequencing (RRBS) from horses 34 and whole-genome bisulfite sequencing data from cattle 35,36 .…”

“…Mean methylation level in blood according to the mammalian array (x axis) versus corresponding mean values according to a reduced representation bisulfite sequencing and b wholegenome bisulfite sequencing in blood from horse and cattle, respectively. The mammalian methylation array data come from horse blood 32 and cattle blood 33 . a The y axis reports the mean methylation levels in RRBS data from n = 18 whole blood samples from horses 34 .…”

“…The cattle data generated on the mammalian array were not generated for this study. These data are presented in another article 33 and can be requested from SH. The mammalian methylation array (HorvathMammalMethylChip40) is registered at the NCBI Gene Expression Omnibus (GEO) as platform GPL28271.…”

Epigenetic clock and methylation studies in gray short-tailed opossums

“…We previously developed dual species clocks for different placental species [32][33][34][35][36][37][38][39][40]. A critical step toward building dual species clocks was the development and use of a mammalian DNA methylation array that profiles CpGs with flanking DNA sequences that are highly conserved across numerous mammalian species.…”

“…DNA methylation-based age estimators have been developed for many mammalian species but not yet for opossums [32][33][34][35][36][37][38][39][40]. Here, we present highly accurate epigenetic clocks that apply to both humans and opossum.…”