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Abstract Exposure to pathogens throughout a lifetime influences immunity and organ function. Here, we explore how the systemic host-response to bacterial urinary tract infection (UTI) induces tissue-specific alterations to the mammary gland. Utilizing a combination of histological tissue analysis, single cell transcriptomics, and flow cytometry, we identify that mammary tissue from UTI-bearing mice displays collagen deposition, enlarged ductal structures, ductal hyperplasia with atypical epithelial transcriptomes and altered immune composition. Bacterial cells are absent in the mammary tissue and blood of UTI-bearing mice, therefore, alterations to the distal mammary tissue are mediated by the systemic host response to local infection. Furthermore, broad spectrum antibiotic treatment resolves the infection and restores mammary cellular and tissue homeostasis. Systemically, unresolved UTI correlates with increased plasma levels of the metalloproteinase inhibitor, TIMP1, which controls extracellular matrix remodeling and neutrophil function. Treatment of nulliparous and post-lactation UTI-bearing female mice with a TIMP1 neutralizing antibody, restores mammary tissue normal homeostasis, thus providing evidence for a link between the systemic host response during UTI and mammary gland alterations. 

Abstract The evolutionary direction of gonochorism and hermaphroditism is an intriguing mystery to be solved. The special transient hermaphroditic stage makes the little yellow croaker (Larimichthys polyactis) an appealing model for studying hermaphrodite formation. However, the origin and evolutionary relationship between ofL. polyactisandLarimichthys crocea, the most famous commercial fish species in East Asia, remain unclear. Here, we report the sequence of theL. polyactisgenome, which we found is ~706 Mb long (contig N50 = 1.21 Mb and scaffold N50 = 4.52 Mb) and contains 25,233 protein‐coding genes. Phylogenomic analysis suggested thatL. polyactisdiverged from the common ancestor,L. crocea, approximately 25.4 million years ago. Our high‐quality genome assembly enabled comparative genomic analysis, which revealed several within‐chromosome rearrangements and translocations, without major chromosome fission or fusion events between the two species. Thedmrt1gene was identified as the male‐specific gene inL. polyactis. Transcriptome analysis showed that the expression ofdmrt1and its upstream regulatory gene (rnf183) were both sexually dimorphic.Rnf183, unlike its two paraloguesrnf223andrnf225, is only present inLarimichthysandLatesbut not in other teleost species, suggesting that it originated from lineage‐specific duplication or was lost in other teleosts.Phylogenetic analysis shows that the hermaphrodite stage in maleL. polyactismay be explained by the sequence evolution ofdmrt1. Decoding theL. polyactisgenome not only provides insight into the genetic underpinnings of hermaphrodite evolution, but also provides valuable information for enhancing fish aquaculture.