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 biological age of oocytes. Both epigenetic clock studies and epigenome‐wide association studies revealed that blood and oocytes differ substantially with respect to 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.

Highlights

  • The mammalian female reproductive axis is the first to fail in aging; the molecular mechanisms underpinning this failure are largely unknown, in oocytes (Chamani & Keefe, 2019; Garg & Sinclair, 2015; Homer, 2020)

  • DNA methylation data were generated from DNA samples (n = 357) from oocyte donors (n = 80) and blood donors (n = 277) of cattle (Bos taurus)

  • Several highly accurate epigenetic clocks were developed for cattle blood, cattle oocytes, and both tissues combined (Figure 1a-­ c)

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Summary

Introduction

The mammalian female reproductive axis is the first to fail in aging; the molecular mechanisms underpinning this failure are largely unknown, in oocytes (Chamani & Keefe, 2019; Garg & Sinclair, 2015; Homer, 2020). Fertility in women begins to decline significantly by their mid-­30 s and pregnancies in women of advanced age lead to higher rates of miscarriage and/or aneuploid offspring (Baired et al, 2005) Despite these risks, women and couples often postpone pregnancy to a more convenient time which has led to a decline in birthrate among most industrialized societies (Homer, 2020; Navot et al, 1991). Women and couples often postpone pregnancy to a more convenient time which has led to a decline in birthrate among most industrialized societies (Homer, 2020; Navot et al, 1991) This decline in fertility can be explained by the age-­related decline in oocyte quality which manifests itself by chromosomal abnormalities, spindle defects, mitochondrial dysfunction, and epigenetic modifications (Baired et al, 2005; Kikuchi et al, 2000; Liu et al, 2002; López-­Otín et al, 2013; Pellestor et al, 2003; Xu et al, 1997).

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