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DNA methylation differences underlying female reproductive aging

ABSTRACT: Reproductive aging occurs earlier than systemic aging as a woman’s ovarian reserve is depleted as she approaches menopause. There is considerable variability around when a woman reaches menopause, yet few contributing factors have been identified. Assessment of reproductive age involves measuring a woman’s ovarian reserve and oocyte function, which has clearly-defined parameters in in vitro fertilization. As ovarian reserve declines, Anti-Mullerian hormone levels fall and women produce fewer oocytes after ovarian stimulation. Oocyte function also declines, as fewer mature oocytes are produced and have the capacity to be fertilized. The mechanisms of these age-related declines are unclear, but may involve changes in DNA methylation, which are known to occur with age and may reflect the biological processes underlying reproductive aging. We hypothesize that DNA methylation patterns will be associated with ovarian reserve and oocyte function, and that women with poor ovarian reserve and oocyte function will experience epigenetic age acceleration and will accumulate more stochastic epigenetic mutations. To test this hypothesis, we will first perform an epigenome-wide association to examine DNA methylation patterns associated with each measure of ovarian reserve and oocyte function. Then, we will calculate epigenetic age and age acceleration, which are indicators of biological aging, and stochastic epigenetic mutations, which increase with age and may disrupt key biological pathways in an individual.

ORGANISM(S): Homo sapiens

PROVIDER: GSE293125 | GEO | 2026/03/27

REPOSITORIES: GEO

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Project description:Infertility affects approximately 10% of women in the United States and is increasingly becoming more common. Recent studies suggest that, in addition to its reproductive consequences, infertility is associated with the development of chronic disease and all-cause mortality. Two examples of this phenomenon that are supported by the literature are risks of cardiovascular disease (CVD) and metabolic syndrome (MetS), both of which are more common in women and have elevated risks after menopause. CVD is the leading cause of death in women, and MetS has a prevalence of approximately 30% and increases risk for mortality. It is likely that there are shared pathways between infertility and CVD and MetS, such as increased inflammation, which may modulate risk for both conditions. Thus evaluating women with infertility for future CVD and MetS provides a unique opportunity for preventative measures and personalized treatments within the context of infertility evaluations. One way to identify women at increased risk for CVD and MetS is through examining differences in DNA methylation. DNA methylation is one mechanism through which gene expression responds to changes in the environment, hormone status, or other physiologic processes. These changes may occur prior to the onset of symptomatic disease and can identify women at increased risk for adverse outcomes. This study will evaluate three DNA methylation-based predictors of long-term health, CVD, and MetS in women with infertility and women without infertility who are undergoing in vitro fertilization. We will also evaluate associations with low ovarian reserve, which is predictive of time to menopause and may also associate with increased risk. First, we will assess an indicator of cellular age acceleration that is predictive of health-span and all-cause mortality. Then, we will leverage combinations of CpG sites to predict a CVD methylation risk score and a separate MetS methylation risk score. We hypothesize that infertility and low ovarian reserve will be associated with increased age acceleration, which would serve as a general marker of future disease and mortality. We hypothesize that the CVD methylation risk score will be associated with infertility and low ovarian reserve due to putative links between infertility and later development of CVD. Finally, we hypothesize that infertility and low ovarian reserve will be associated with increased MetS methylation risk scores as obesity and other MetS risk factors play a role in infertility.

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	GSE293125_RAW.tar	Raw
	GSE293125_REI_K01_EPICv2_110524_betas_without_suffix_passQC.csv.gz	Csv
	filelist.txt	Txt

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DNA methylation differences underlying female reproductive aging

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