The effects of superovulation and reproductive aging on the epigenome of the oocyte and embryo

Abstract

A societal preference of delaying maternal age at first childbirth has increased reliance on assisted reproductive technologies/therapies (ART) to conceive a child. Oocytes that have undergone physiologic aging (≥35 years for humans) are now commonly used for ART, yet evidence is building that suboptimal reproductive environments associated with aging negatively affect oocyte competence and embryo development-although the mechanisms underlying these relationship are not yet well understood. Epigenetic programming of the oocyte occurs during its growth within a follicle, so the ovarian stimulation protocols that administer exogenous hormones, as part of the first step for all ART procedures, may prevent the gamete from establishing an appropriate epigenetic state. Therefore, understanding how oocyte. Therefore, understanding how hormone stimulation and oocyte physiologic age independently and synergistically physiologic age independently and synergistically affect the epigenetic programming of these gametes, and how this may affect their developmental competence, are crucial to improved ART outcomes. Here, we review studies that measured the developmental outcomes affected by superovulation and aging, focusing on how the epigenome (i.e., global and imprinted DNA methylation, histone modifications, and epigenetic modifiers) of gametes and embryos acquired from females undergoing physiologic aging and exogenous ovarian stimulation is affected.

Antioxidant hesperetin improves the quality of porcine oocytes during aging in vitro

“…Developmental rate determines the efficiency with which embryos are produced in vitro. Aging negatively affects oocyte competency and embryo development (Marshall & Rivera, ), and reduces the cleavage rate (W. J. Yang et al, ). The percentage of oocytes that became cleavage was similar in the control and H‐100 groups, and was lower in the aging group than in the control group.…”

“…Developmental rate determines the efficiency with which embryos are produced in vitro. Aging negatively affects oocyte competency and embryo development (Marshall & Rivera, 2018), and reduces the cleavage rate (W. J. Yang et al, 2015).…”

Increased transcriptome variation and localised DNA methylation changes in oocytes from aged mice revealed by parallel single‐cell analysis

“…Amongst the key molecular changes found to occur in oocytes from aged females are mitochondrial dysfunction, telomere shortening, cohesin dysfunction resulting in spindle instability and reduced stringency in spindle assembly checkpoints (Reviewed in Cimadomo et al, 2018;Vollenhoven & Hunt, 2018). In recent years, it has been proposed that transcriptional and epigenetic changes, especially DNA methylation, may contribute to compromised oocyte quality with advanced maternal age (Cimadomo et al, 2018;Ge et al, 2015;Marshall & Rivera, 2018). The changing environment to which an oocyte is exposed in the ageing ovary, such as altered hormone levels, and changes in energy and one-carbon metabolism, could affect gene expression and epigenetic processes that could contribute to the lower developmental capacity of oocytes with age (Ge et al, 2015).…”

Identification and characterization of human ovary-derived circular RNAs and their potential roles in ovarian aging

“…Poor oocyte quality, including meiotic abnormalities, mitochondrial defects, and ooplasm quality, are clearly linked to adverse reproductive outcomes [ 4 ]. Given the role of the epigenome in controlling gene expression and chromatin structure, it is likely a contributor to the decline in fecundity in aging females [ 5 ]. Non-coding RNAs (ncRNAs), such as miRNAs, piRNAs, and lncRNAs, are important regulators of gene expression, particularly at the post transcriptional level, and are important members of the epigenetic regulation network [ 6 ].…”