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      Liver transcriptome profiling and functional analysis of intrauterine growth restriction (IUGR) piglets reveals a genetic correction and sexual-dimorphic gene expression during postnatal development

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          Abstract

          Background

          Intrauterine growth restriction (IUGR) remains a major problem associated with swine production. Thus, understanding the physiological changes of postnatal IUGR piglets would aid in improving growth performance. Moreover, liver metabolism plays an important role in the growth and survival of neonatal piglets.

          Results

          By profiling the transcriptome of liver samples on postnatal Days 1, 7, and 28, our study focused on characterizing the growth, function, and metabolism in the liver of IUGR neonatal piglets. Our study demonstrates that the livers of IUGR piglets were associated with a series of complications, including inflammatory stress and immune dysregulation; cytoskeleton and membrane structure disorganization; dysregulated transcription events; and abnormal glucocorticoid metabolism. In addition, the abnormal liver function index in the serum [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total protein (TP)], coupled with hepatic pathological and ultrastructural morphological changes are indicative of liver damage and dysfunction in IUGR piglets. Moreover, these results reveal the sex-biased developmental dynamics between male and female IUGR piglets, and that male IUGR piglets may be more sensitive to disrupted metabolic homeostasis.

          Conclusions

          These observations provide a detailed reference for understanding the mechanisms and characterizations of IUGR liver functions, and suggest that the potential strategies for improving the survival and growth performance of IUGR offspring should consider the balance between postnatal catch-up growth and adverse metabolic consequences. In particular, sex-specific intervention strategies should be considered for both female and male IUGR piglets.

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          Most cited references47

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          Cell mechanics and the cytoskeleton.

          The ability of a eukaryotic cell to resist deformation, to transport intracellular cargo and to change shape during movement depends on the cytoskeleton, an interconnected network of filamentous polymers and regulatory proteins. Recent work has demonstrated that both internal and external physical forces can act through the cytoskeleton to affect local mechanical properties and cellular behaviour. Attention is now focused on how cytoskeletal networks generate, transmit and respond to mechanical signals over both short and long timescales. An important insight emerging from this work is that long-lived cytoskeletal structures may act as epigenetic determinants of cell shape, function and fate.
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            Immune Responses in the Liver.

            The liver is a key, frontline immune tissue. Ideally positioned to detect pathogens entering the body via the gut, the liver appears designed to detect, capture, and clear bacteria, viruses, and macromolecules. Containing the largest collection of phagocytic cells in the body, this organ is an important barrier between us and the outside world. Importantly, as portal blood also transports a large number of foreign but harmless molecules (e.g., food antigens), the liver's default immune status is anti-inflammatory or immunotolerant; however, under appropriate conditions, the liver is able to mount a rapid and robust immune response. This balance between immunity and tolerance is essential to liver function. Excessive inflammation in the absence of infection leads to sterile liver injury, tissue damage, and remodeling; insufficient immunity allows for chronic infection and cancer. Dynamic interactions between the numerous populations of immune cells in the liver are key to maintaining this balance and overall tissue health.
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              Sex differences in developmental programming models.

              The theory of developmental programming suggests that diseases such as the metabolic syndrome may be 'programmed' by exposure to adverse stimuli during early development. The developmental programming literature encompasses the study of a wide range of suboptimal intrauterine environments in a variety of species and correlates these with diverse phenotypic outcomes in the offspring. At a molecular level, a large number of variables have been measured and suggested as the basis of the programmed phenotype. The range of both dependent and independent variables studied often makes the developmental programming literature complex to interpret and the drawing of definitive conclusions difficult. A common, though under-explored, theme of many developmental programming models is a sex difference in offspring outcomes. This holds true across a range of interventions, including dietary, hypoxic, and surgical models. The molecular and phenotypic outcomes of adverse in utero conditions are often more prominent in male than female offspring, although there is little consideration given to the basis for this observation in most studies. We review the evidence that maternal energy investment in male and female conceptuses may not be equal and may be environment dependent. It is suggested that male and female development could be viewed as separate processes from the time of conception, with differences in both timing and outcomes.
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                Author and article information

                Contributors
                iaswlx@263.net
                Journal
                BMC Genomics
                BMC Genomics
                BMC Genomics
                BioMed Central (London )
                1471-2164
                8 October 2020
                8 October 2020
                2020
                : 21
                : 701
                Affiliations
                GRID grid.410727.7, ISNI 0000 0001 0526 1937, Institute of Animal Science, , Chinese Academy of Agricultural Sciences, ; Beijing, 100193 P. R. China
                Author information
                http://orcid.org/0000-0002-1852-7308
                Article
                7094
                10.1186/s12864-020-07094-9
                7545842
                33032518
                5d5db613-8a52-4a88-a55d-e78fa4759188
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 5 February 2020
                : 23 September 2020
                Funding
                Funded by: National Key R&D Program of China
                Award ID: 2017YFD0501901
                Award Recipient :
                Funded by: Beijing Natural Science Foundation
                Award ID: 6164041
                Award Recipient :
                Funded by: Agricultural Science and Technology Innovation Program
                Award ID: ASTIP-IAS02
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 31872337
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Genetics
                intrauterine growth restriction (iugr),piglets,liver,transcriptome,sexual dimorphism
                Genetics
                intrauterine growth restriction (iugr), piglets, liver, transcriptome, sexual dimorphism

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