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In Utero Heat Stress Alters the Offspring Epigenome.

ABSTRACT: Exposure to intrauterine heat stress during late gestation affects offspring performance into adulthood. However, underlying mechanistic links between thermal insult in fetal life and postnatal outcomes are not completely understood. We examined morphology, DNA methylation, and gene expression of liver and mammary gland for bull calves and heifers that were gestated under maternal conditions of heat stress or cooling (i.e. in utero heat stressed vs. in utero cooled calves). Mammary tissue was harvested from dairy heifers during their first lactation and liver from bull calves at birth. The liver of in utero heat stressed bull calves contained more cells and the mammary glands of in utero heat stressed heifers were comprised of smaller alveoli. We identified more than 1,500 CpG sites differently methylated between maternal treatment groups. These CpGs were associated with approximately 400 genes, which play a role in processes, such as development, innate immune defense, cell signaling, and transcription and translation. We also identified over 100 differentially expressed genes in the mammary gland with similar functions. Interestingly, fifty differentially methylated genes were shared by both bull calf liver and heifer mammary gland. Intrauterine heat stress alters the methylation profile of liver and mammary DNA and programs their morphology in postnatal life, which may contribute to the poorer performance of in utero heat stressed calves.

SUBMITTER: Skibiel AL

PROVIDER: S-EPMC6168509 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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In Utero Heat Stress Alters the Offspring Epigenome.

Skibiel A L AL Peñagaricano F F Amorín R R Ahmed B M BM Dahl G E GE Laporta J J

Scientific reports 20181002 1

Exposure to intrauterine heat stress during late gestation affects offspring performance into adulthood. However, underlying mechanistic links between thermal insult in fetal life and postnatal outcomes are not completely understood. We examined morphology, DNA methylation, and gene expression of liver and mammary gland for bull calves and heifers that were gestated under maternal conditions of heat stress or cooling (i.e. in utero heat stressed vs. in utero cooled calves). Mammary tissue was ha ...[more]

PMID: 30279561

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Project description:The effects of in utero heat stress (IUHS) range from decreased growth performance to altered behavior, but the long-term impact of IUHS on postnatal innate immune function in pigs is unknown. Therefore, the study objective was to determine the effects of early gestation IUHS on the immune, metabolic, and stress response of pigs subjected to an 8 hr lipopolysaccharide (LPS) challenge during postnatal life. Twenty-four pregnant gilts were exposed to thermoneutral (TN; n = 12; 17.5 ± 2.1 °C) or heat stress (HS; n = 12; cyclic 26 to 36 °C) conditions from days 6 to 59 of gestation, and then TN conditions (20.9 ± 2.3 °C) from day 60 of gestation to farrowing. At 12 wk of age, 16 IUHS and 16 in utero thermoneutral (IUTN) pigs were selected, balanced by sex and given an intravenous injection of LPS (2 µg/kg BW mixed with sterile saline [SAL] and injected at 2 µL/kg BW) or SAL (2 µL/kg BW). Body temperature was monitored every 30 min, and blood was obtained at 0, 1, 2, 3, 4, 6, and 8 hr following the LPS challenge. Blood samples were analyzed for glucose, insulin, non-esterified fatty acids (NEFA), cortisol, and cytokine concentrations. In addition, white blood cell counts were determined at 0 and 4 hr. Hour 0 data were used as covariates. Body temperature was increased (P < 0.01) in LPS (40.88 ± 0.08 °C) vs. SAL (39.83 ± 0.08 °C) pigs. Eosinophils tended to be decreased overall (P = 0.09; 43.9%) in IUHS vs. IUTN pigs. Glucose concentrations were reduced overall (P = 0.05; 5.9%) in IUHS vs. IUTN pigs. The NEFA concentrations tended to be greater (P = 0.07; 143.4%) in IUHS-LPS pigs compared with all other treatments, and IUTN-LPS pigs tended to have greater (127.4%) circulating NEFA concentrations compared with IUTN-SAL and IUHS-SAL pigs. Cortisol was increased (P = 0.04) in IUHS-LPS compared with IUTN-LPS pigs at 3 hr (21.5%) and 4 hr (64.3%). At 1 hr, tumor necrosis factor α was increased (P = 0.01; 115.1%) in IUHS-LPS compared with IUTN-LPS pigs. Overall, interleukin-1β (IL-1β) and interleukin-6 (IL-6) were greater (P < 0.04; 281.3% and 297.8%, respectively) in IUHS-LPS pigs compared with all other treatments, and IUTN-LPS pigs had increased IL-1β and IL-6 concentrations compared with IUTN-SAL and IUHS-SAL pigs. In summary, IUHS altered the postnatal cytokine, metabolic, and physiological stress response of pigs during postnatal life, which may have negative implications toward the innate immune response of IUHS pigs to pathogens.

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In Utero Heat Stress Alters the Offspring Epigenome.

Publications

In Utero Heat Stress Alters the Offspring Epigenome.

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