Lactocrine insufficiency at birth impacts uterine gene expression and development in postnatal day 14 pigs

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ID: 325901
2026
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Abstract
Abstract Maternal effects on offspring development do not end at birth. Bioactive factors are transmitted from mothers to nursing offspring through colostrum, by a process known as lactocrine signaling. In pigs, naturally occurring lactocrine insufficiency, indicated by reduced serum immunoglobulin immunocrit (iCrit) ratios within 24-h of postnatal life, impaired uterine development and reduced adult fecundity. This effect was evaluated at postnatal day (PND) 14 with histology and transcriptomics on six pairs of littermates with high- vs. low-iCrit measured at PND 1. RNA-seq analysis identified 148 differentially expressed genes (DEGs) between groups (P<0.05) and eight DEGs were validated by qRT-PCR (P<0.05), including FOXA2, a gene with well-established expression in the uterine glandular epithelium (GE) across multiple mammalian species. Immunohistochemistry confirmed FOXA2 localization in the PND 14 pig uterus, and lactocrine deficiency reduced endometrial glandularity, supported by fewer GE cells/mm2 in low versus high iCrit gilts (P<0.05). Downregulated genes in uteri from low-iCrit gilts were associated with growth, differentiation, and secretion, whereas upregulated genes were enriched for immune processes, including complement activation and cytokine signaling. These findings suggest that inadequate colostrum-derived antibodies trigger uterine immune activation at PND 14, potentially impairing development and reducing adult uterine capacity. Highly expressed genes in PND 14 pig uterus were enriched for structural, developmental, and growth functions and included a subset of tissue-specific genes shared between pigs and humans. Integration of pig and human GTEx datasets identified conserved and species-specific uterine-biased genes, including DEG between high- and low-iCrit gilts, highlighting potential uterine biomarkers of early uterine development.
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Authors Xiaolei Ma, Hiruni R Wijesena, Ying Zhang, Jeremy R. Miles, William T. Oliver, Wenqi Cao, Nina Paranjpe, Frank F. Bartol, Clay A Lents, Carol A. Bagnell, Xu Wang
Journal biology of reproduction
Year 2026
DOI
10.1093/biolre/ioag181
URL
https://doi.org/10.1093/biolre/ioag181
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