title: Age and Nursing Affect the Neonatal Porcine Uterine Transcriptome.
abstract: The lactocrine hypothesis for maternal programming of neonatal development was proposed to describe a mechanism through which milk-borne bioactive factors, delivered from mother to nursing offspring, could affect development of tissues, including the uterus. Porcine uterine development, initiated before birth, is completed postnatally. However, age- and lactocrine-sensitive elements of the neonatal porcine uterine developmental program are undefined. Here, effects of age and nursing on the uterine transcriptome for 48 h from birth (Postnatal Day [PND] = 0) were identified using RNA sequencing (RNAseq). Uterine tissues were obtained from neonatal gilts (n = 4 per group) within 1 h of birth and before feeding (PND 0), or 48 h after nursing ad libitum (PND 2N) or feeding a commercial milk replacer (PND 2R). RNAseq analysis revealed differentially expressed genes (DEGs) associated with both age (PND 2N vs. PND 0; 3283 DEGs) and nursing on PND 2 (PND 2N vs PND 2R; 896 DEGs). Expression of selected uterine genes was validated using quantitative real-time PCR. Bioinformatic analyses revealed multiple biological processes enriched in response to both age and nursing, including cell adhesion, morphogenesis, and cell-cell signaling. Age-sensitive pathways also included estrogen receptor-alpha and hedgehog signaling cascades. Lactocrine-sensitive processes in nursed gilts included those involved in response to wounding, the plasminogen activator network and coagulation. Overall, RNAseq analysis revealed comprehensive age- and nursing-related transcriptomic differences in the neonatal porcine uterus and identified novel pathways and biological processes regulating uterine development.
authors.affiliation: United States Department of Agriculture, Agriculture Research Service, Clay Center, Nebraska Department of Animal Sciences, Endocrinology and Animal Biosciences Program, Rutgers University, New Brunswick, New Jersey.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Rahman
authors.affiliation: Department of Animal Sciences, Endocrinology and Animal Biosciences Program, Rutgers University, New Brunswick, New Jersey.
authors.forename: Meredith E
authors.initials: ME
authors.lastname: Camp
authors.affiliation: Genomic Services Laboratory, HudsonAlpha Institute for Biotechnology, Huntsville, Alabama.
authors.forename: Nripesh
authors.initials: N
authors.lastname: Prasad
authors.affiliation: United States Department of Agriculture, Agriculture Research Service, Clay Center, Nebraska.
authors.forename: Anthony K
authors.initials: AK
authors.lastname: McNeel
authors.affiliation: Genomic Services Laboratory, HudsonAlpha Institute for Biotechnology, Huntsville, Alabama.
authors.forename: Shawn E
authors.initials: SE
authors.lastname: Levy
authors.affiliation: Department of Anatomy, Physiology, and Pharmacology, Cellular and Molecular Biosciences Program, Auburn University, Auburn, Alabama.
authors.forename: Frank F
authors.initials: FF
authors.lastname: Bartol
authors.affiliation: Department of Animal Sciences, Endocrinology and Animal Biosciences Program, Rutgers University, New Brunswick, New Jersey bagnell@aesop.rutgers.edu.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Bagnell
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007774:Lactation / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013552:Swine; D059467:Transcriptome; D014599:Uterus / Q000378:metabolism*
keywords: developmental biology; gene expression; genomics; lactocrine; neonatal; nursing; porcine/pig; transcriptome; uterus