(EA03-09-25) Parental Housing Temperature Modulates Sperm DNA Methylation and Shapes Offspring Metabolic and Adipose Tissue Outcomes

Scientific conference where the work was recently presented: Obesity and Adipose Tissue Keystone

Date on which the work was previously presented at the scientific conference listed: February 2025

Objectives: This study examines how pre-conception and gestational housing temperatures influence diet-induced metabolic stress in offspring.

Methods: Male and female mice were housed at either 8°C (cold exposed, CE) or 30°C (Thermoneutral, TN) 1wk prior to conception and 3wk during gestation. Sperm samples from male mice were collected, and DNA was isolated to determine the epigenetic landscape using Reduced Representation Bisulfite Sequencing (RRBS) assay. Offspring born to CE and TN parents were exposed to control (CEC, TNC) and high-fat diet (CEHF, TNHF) respectively for 12wk, and various metabolic parameters were measured. Following euthanasia, adipose tissue depots were collected and analyzed.

Results: Epigenetic analysis using RRBS revealed persistent changes in paternal sperm DNA methylation caused by housing temperature. Male offspring born to TN parents and fed a high-fat diet (TNHF) exhibited greater body weight gains than their CEHF counterparts, while female offspring showed the opposite trend, with higher weight gain in CEHF than TNHF. At weaning, no significant differences in body composition were observed among the four groups, regardless of sex. At 15 weeks of age, TNHF males displayed significantly greater diet-induced fat accumulation compared to CEHF males. In contrast, diet-induced fat gain in females did not differ significantly between offspring born to CE and TN parents. Histological analysis of adipose tissue depots revealed larger adipocytes in HFD-fed offspring born to TN parents than those born to CE parents. Moreover, UCP1 expression in brown adipose tissue (BAT) varied with both parental temperatures and offspring sex in response to diet. In females, parental temperature also influenced the diet-induced expression of DIO2 in BAT and CCL4 in inguinal white adipose tissue (iWAT).

Conclusions: Parental housing temperature in rodents has a long-lasting effect on offspring traits, particularly in shaping body weight, fat distribution, and adipose tissue structure. The complex interaction between genetic and environmental factors, reflected in epigenetic modifications, highlights the multifaceted nature of metabolic programming.

Funding Sources: Funded by the Center for Childhood Obesity Prevention funded by the National Institutes of Health (P20GM109096).