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

Authors: MA, XIAOLEI - Auburn University; Wijesena, Hiruni; ZHANG, YING - Auburn University; Miles, Jeremy; Oliver, William; CAO, WENQI - Auburn University; PARANJPE, NINA - Rutgers University; BARTOL, FRANK - Auburn University; Lents, Clay; BAGNELL, CAROL - Rutgers University; WANG, XU - Auburn University

Submitted to: Biology of Reproduction
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/20/2026
Publication Date: 8/22/2026
Citation: Ma, X., Wijesena, H.R., Zhang, Y., Miles, J.R., Oliver, W.T., Cao, W., Paranjpe, N., Bartol, F.F., Lents, C.A., Bagnell, C.A., Wang, X. 2026. Lactocrine insufficiency at birth impacts uterine gene expression and development in postnatal day 14 pigs. Biology of Reproduction. Article ioag181. https://doi.org/10.1093/biolre/ioag181.
DOI: https://doi.org/10.1093/biolre/ioag181

Interpretive Summary: Mothers pass vital factors through milk colostrum to offspring during nursing, a process called lactorcrine programming. This critically influences offspring development beyond birth. In pigs, insufficient lactocrine programming can be measured shortly after birth with a test called the iCrit. When pigs have a low iCrit at birth, they produce fewer offspring when they become adult mothers. To understand why this happens, USDA scientists at Clay Center, Nebraska, in collaboration with Rutgers University and Auburn University studied early development of the uterus in pigs with high iCrit and compared it to pigs with low iCrit. Major differences were observed in gene expression as early as 14 days of age between pigs with different iCrit tests. These changes in gene expression in low iCrit pigs were associated with decreased development of tissue layers in the uterus that are important for supporting pregnancy. This research links reductions in pregnancy of adult pigs to critical nursing events during the first day of their life. Farmers will use this information to manage nursing programs to enhance piglet health and improve breeding success of mothers.

Technical 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 from birth, 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 0. RNA-seq analysis identified 148 differentially expressed genes (DEG) between groups (P<0.05) and eight DEG was 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 DEG in low-iCrit gilts are associated with growth, differentiation, and secretion, whereas upregulated genes are 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 uterus-biased genes, including DEG between high- and low-iCrit gilts, highlighting potential uterine biomarkers of early uterine development.