Cold exposure during early pregnancy altered breast milk bile acids and microbial metabolism, providing male rat offspring with lasting protection against impaired glucose control and liver fat accumulation, according to a Jul. 12 report.
Researchers publishing in the journal npj Biofilms and Microbiomes evaluated whether maternal cold exposure during early pregnancy influenced long-term metabolic outcomes in offspring. The study used immunophenotyping, transcriptomic, metabolomic, and cross-fostering approaches. Results showed that male offspring of cold-exposed mothers had significantly improved glucose tolerance, insulin sensitivity, and hepatic lipid profiles when challenged with a Western diet. These benefits persisted into late adulthood for males maintained on standard chow.
Mechanistic evaluations indicated that these effects were transmitted at least partly through postnatal factors associated with lactation. Lithocholic acid (LCA)-enriched breast milk was identified as a potential mediator. In vivo model findings were complemented by observational human analyses where winter conception—used as a proxy for early-pregnancy cold exposure—was associated with lower risk of metabolic dysfunction-associated steatotic liver disease (MASLD).
The researchers experimentally exposed pregnant rats to either room temperature or cold conditions during the first 10 days of gestation. Offspring were then raised at room temperature until weaning before dietary interventions began. Cross-fostering experiments exchanged newborn pups between cold-exposed and room-temperature mothers within 24 hours of birth to isolate prenatal versus postnatal impacts.
Long-term metabolic changes were assessed using molecular assays including LC-MS/MS for metabolomic profiling of maternal breast milk and offspring plasma; flow cytometry for immune cell evaluation; and transcriptomic profiling via RNA sequencing and qRT-PCR for liver tissue alterations. Human data from UK Biobank participants and the China Health and Retirement Longitudinal Study supported the animal findings associating winter conception with reduced MASLD risk in colder climates.
The authors noted that while results support a maternal cold-milk bile acid-microbiota-T helper 17 axis influencing long-term metabolic health in male rat offspring, further studies are needed to establish whether this mechanism operates similarly in humans or could inform future interventions.
