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ZFP57 is a regulator of postnatal growth and life-long health

ABSTRACT: Early-life factors, including nutrition, shape long-term health outcomes. Despite the essential role of lactation in maternal nutritional support, the influence of epigenetic factors on lactation and postnatal growth remains poorly understood. Zinc-finger protein 57 (ZFP57), is an epigenetic regulator of genomic imprinting, a process that directs gene expression based on parental origin, playing a vital role in mammalian prenatal growth. Here, we identify a novel function of ZFP57 in the mammary glandI, where it serves as a key modulator of postnatal resource control, independently of imprinted genes. ZFP57 regulates multiple aspects of mammary gland functions, including ductal branching and cellular homeostasis. Its absence leads to significant differential gene expression, related to alveologenesis, lactogenesis and milk synthesis, associated with delayed lactation and altered milk composition. This results in life-long impacts on offspring including the development of metabolic syndrome. Cross-fostering reveals intricate dynamics between mother and offspring during lactation. Pups raised by a dam of a different genotype than their birth mother exhibit exacerbated metabolic features in adulthood, providing additional novel insight into the programming of offspring long-term health by maternal context. This study deepens our understanding of the interplay between epigenetic factors, lactation, and postnatal resource control.

ORGANISM(S): Mus musculus

PROVIDER: GSE248780 | GEO | 2024/07/31

REPOSITORIES: GEO

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Project description:Production of milk is a key characteristic of mammals, but the features of lactation vary greatly between monotreme, marsupial and eutherian mammals. Marsupials have a short gestation followed by a long lactation period, and the milk constituents vary greatly across lactation to meet the changing needs of the developing young. Marsupials are born immunologically naïve and rely on their mother’s milk for immunological protection. The koala is an iconic Australian species and many are increasingly threatened by disease. Here we use a mammary transcriptome, two milk proteomes and the koala genome to comprehensively characterise the protein components of the milk of the koala, with a key focus on the immune constituents during early and late lactation. We have characterised the most abundant peptides present in milk, examined key differences between early and late lactation, and determined differences between the koala and other marsupial species. The most abundant proteins were well characterised mammalian and marsupial-specific milk proteins including β-lactoglobulin, lactotransferrin, caseins and early lactation protein. We have generated a list of 851 immune compounds identified in the mammary transcriptome and examined a range of immune proteins that were highly abundant in the milk proteomes. These include immunoglobulins, complement components and immune receptors. A host of antimicrobial peptides were identified including cathelicidins, lysozyme, WAP four-disulfide core domain protein 2, Mucin-1 and Peptidoglycan recognition protein. We discovered that the previously described marsupial milk protein Very Early Lactation Protein is an ortholog of the eutherian gene Glycam1 (PP3) and likely has an antimicrobial role in milk. We also identified highly abundant koala endogenous retrovirus sequences in the mammary and milk transcriptome and proteomes, identifying a potential route for retroviral transmission from mother to young. Identifying and characterising the immune components of milk is key to understanding how marsupial young are protected throughout lactation and the novel immune compounds identified may have applications in clinical research.

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ZFP57 is a regulator of postnatal growth and life-long health

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