Male obesity impacts DNA methylation reprogramming in sperm.

Abstract:

BACKGROUND:Male obesity has profound effects on morbidity and mortality, but relatively little is known about the impact of obesity on gametes and the potential for adverse effects of male obesity to be passed to the next generation. DNA methylation contributes to gene regulation and is erased and re-established during gametogenesis. Throughout post-pubertal spermatogenesis, there are continual needs to both maintain established methylation and complete DNA methylation programming, even during epididymal maturation. This dynamic epigenetic landscape may confer increased vulnerability to environmental influences, including the obesogenic environment, that could disrupt reprogramming fidelity. Here we conducted an exploratory analysis that showed that overweight/obesity (n = 20) is associated with differences in mature spermatozoa DNA methylation profiles relative to controls with normal BMI (n = 47). RESULTS:We identified 3264 CpG sites in human sperm that are significantly associated with BMI (p < 0.05) using Infinium HumanMethylation450 BeadChips. These CpG sites were significantly overrepresented among genes involved in transcriptional regulation and misregulation in cancer, nervous system development, and stem cell pluripotency. Analysis of individual sperm using bisulfite sequencing of cloned alleles revealed that the methylation differences are present in a subset of sperm rather than being randomly distributed across all sperm. CONCLUSIONS:Male obesity is associated with altered sperm DNA methylation profiles that appear to affect reprogramming fidelity in a subset of sperm, suggestive of an influence on the spermatogonia. Further work is required to determine the potential heritability of these DNA methylation alterations. If heritable, these changes have the potential to impede normal development.

journal_name

Clin Epigenetics

journal_title

Clinical epigenetics

authors

Keyhan S,Burke E,Schrott R,Huang Z,Grenier C,Price T,Raburn D,Corcoran DL,Soubry A,Hoyo C,Murphy SK

doi

10.1186/s13148-020-00997-0

subject

Has Abstract

pub_date

2021-01-25 00:00:00

pages

17

issue

1

eissn

1868-7075

issn

1868-7083

pii

10.1186/s13148-020-00997-0

journal_volume

13

pub_type

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