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Cell-Specific Paired Interrogation of the Mouse Ovarian Epigenome and Transcriptome
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Associations between epigenetic age acceleration and infertility.

Yunsung Lee1, Jon Bohlin1, Christian M Page1,2

  • 1Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.

Human Reproduction (Oxford, England)
|June 30, 2022
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Summary

Assisted reproductive technology (ART) use is linked to epigenetic age acceleration in mothers, particularly those with tubal, ovulation, or unexplained infertility. This finding suggests a potential biological link between infertility treatments and aging processes.

Keywords:
in vitro fertilizationNorwegian Motherassisted reproductive technologyather and Child Cohort Studyepigenetic aginginfertilityintracytoplasmic sperm injection

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Area of Science:

  • Epigenetics and aging
  • Reproductive medicine
  • Human cohort studies

Background:

  • Infertility affects a significant portion of the population, prompting the use of assisted reproductive technologies (ART).
  • Epigenetic age acceleration, a measure of biological aging, has been explored as a potential biomarker for health and disease.
  • Previous research has not comprehensively examined the association between ART and epigenetic age acceleration in parents.

Purpose of the Study:

  • To investigate whether the use of ART is associated with epigenetic age acceleration in mothers and fathers.
  • To compare epigenetic age acceleration between ART-conceived and naturally conceived individuals.
  • To explore potential links between specific infertility factors and epigenetic aging.

Main Methods:

  • Utilized data from the Norwegian Mother, Father and Child Cohort Study (MoBa), including 1000 naturally conceived couples and 894 ART-conceived couples (IVF/ICSI).
  • Measured DNA methylation levels using the Illumina MethylationEPIC array to calculate five different epigenetic age accelerations, including Dunedin Pace of Aging methylation (DunedinPoAm).
  • Employed linear mixed models to analyze differences in epigenetic age acceleration between ART and non-ART parents, adjusting for confounders.

Main Results:

  • A significant difference in DunedinPoAm was observed between IVF mothers and non-ART mothers (0.021 years, P=2.89E-06).
  • Elevated DunedinPoAm was found in mothers with tubal factor (0.030 years), ovulation factor (0.023 years), and unexplained infertility (0.023 years) compared to non-ART mothers.
  • No significant differences in epigenetic age accelerations were detected between non-ART and ICSI fathers. DunedinPoAm showed stronger associations with smoking, education, and parity.

Conclusions:

  • ART use, particularly IVF, is associated with epigenetic age acceleration in mothers.
  • Specific infertility factors in mothers are linked to increased epigenetic aging.
  • The findings suggest a potential biological mechanism connecting ART and accelerated aging, possibly related to ovarian reserve, but results should be interpreted with caution due to study limitations.