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Both maternal and offspring Elovl2 genotypes determine systemic DHA levels in perinatal mice.

ABSTRACT: The molecular details relevant to dietary supplementation of the omega-3 fatty acid DHA in mothers as well as in their offspring are not clear. The PUFA elongase, elongation of very long-chain fatty acid (ELOVL)2, is a critical enzyme in the formation of DHA in mammals. In order to address the question regarding the origin of DHA during perinatal life, we have used DHA-deficient Elovl2-ablated mice as a model system to analyze the maternal impact on the DHA level in their offspring of various genotypes. Elovl2^-/- mothers maintained on control diet had significantly lower systemic levels of DHA compared with the Elovl2^+/- and Elovl2^+/+ mothers. Dietary DHA administration during the pregnancy and lactation periods led to increased DHA accretion in maternal tissues and serum of all genotypes. The proportion of DHA in the liver and serum of the Elovl2^-/- offspring was significantly lower than in the Elovl2^+/+ offspring. Remarkably, the DHA level in the Elovl2^+/- offspring nursed by DHA-free-fed Elovl2^-/- mothers was almost as high as in +/+ pups delivered by +/+ mothers, suggesting that endogenous synthesis in the offspring can compensate for maternal DHA deficiency. Maternal DHA supplementation had a strong impact on offspring hepatic gene expression, especially of the fatty acid transporter, Mfsd2a, suggesting a dynamic interplay between DHA synthesis and DHA uptake in the control of systemic levels in the offspring.

SUBMITTER: Pauter AM

PROVIDER: S-EPMC5234714 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Both maternal and offspring Elovl2 genotypes determine systemic DHA levels in perinatal mice.

Pauter Anna M AM Trattner Sofia S Gonzalez-Bengtsson Amanda A Talamonti Emanuela E Asadi Abolfazl A Dethlefsen Olga O Jacobsson Anders A

Journal of lipid research 20161118 1

The molecular details relevant to dietary supplementation of the omega-3 fatty acid DHA in mothers as well as in their offspring are not clear. The PUFA elongase, elongation of very long-chain fatty acid (ELOVL)2, is a critical enzyme in the formation of DHA in mammals. In order to address the question regarding the origin of DHA during perinatal life, we have used DHA-deficient Elovl2-ablated mice as a model system to analyze the maternal impact on the DHA level in their offspring of various ge ...[more]

PMID: 27864326

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Project description:BackgroundBisphenol A (BPA), one of the highest-volume chemicals produced worldwide, has been identified as an endocrine disruptor. Many peer-reviewing studies have reported adverse effects of low dose BPA exposure, particularly during perinatal period (gestation and/or lactation). We previously demonstrated that perinatal oral exposure to BPA (via gavage of mothers during gestation and lactation) has long-term consequences on immune response and intestinal barrier functions. Due to its adverse effects on several developmental and physiological processes, BPA was removed from consumer products and replaced by chemical substitutes such as BPS or BPF, that are structurally similar and not well studied compare to BPA. Here, we aimed to compare perinatal oral exposure to these bisphenols (BPs) at two doses (5 and 50 μg/kg of body weight (BW)/day (d)) on immune response at intestinal and systemic levels in female offspring mice at adulthood (Post Natal Day PND70).MethodsPregnant female mice were orally exposed to BPA, BPS or BPF at 5 or 50 μg/kg BW/d from 15th day of gravidity to weaning of pups at Post-Natal Day (PND) 21. Humoral and cellular immune responses of adult offspring (PND70) were analysed at intestinal and systemic levels.ResultsIn female offspring, perinatal oral BP exposure led to adverse effects on intestinal and systemic immune response that were dependant of the BP nature (A, S or F) and dose of exposure. Stronger impacts were observed with BPS at the dose of 5 μg/kg BW/d on inflammatory markers in feces associated with an increase of anti-E. coli IgG in plasma. BPA and BPF exposure induced prominent changes at low dose in offspring mice, in term of intestinal and systemic immune responses, provoking an intestinal and systemic Th1/Th17 inflammation.ConclusionThese findings provide, for the first time, results of long-time consequences of BPA, S and F perinatal exposure by oral route on immune response in offspring mice. This work warns that it is mandatory to consider immune markers and dose exposure in risk assessment associated to new BPA's alternatives.

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Both maternal and offspring Elovl2 genotypes determine systemic DHA levels in perinatal mice.

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Both maternal and offspring Elovl2 genotypes determine systemic DHA levels in perinatal mice.

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