Nursing During the First Two Days of Life Is Essential for the Expression of Proteins Important for Growth and Remodeling of the Neonatal Porcine Cervix

Abstract

The neonatal porcine cervix is sensitive to hormones, including relaxin (RLX), from birth. Whether nursing is required to establish the cervical developmental program or to determine cervical developmental trajectory is unknown. The objective of study 1 was to determine effects of age and nursing on expression of molecular markers and mediators of porcine cervical growth and remodeling from birth to postnatal day (PND) 2 and to document effects of RLX treatment during this period on expression of targeted gene products in nursed vs. replacer-fed gilts. Study 2 was conducted to determine effects of age at first nursing and duration of nursing from birth on expression of targeted transcripts or proteins at PND 14. Nursing supported cervical estrogen receptor-α, vascular endothelial growth factor, matrix metalloproteinase (MMP)9, and antiapoptotic B-cell lymphoma-2 protein expression on PND 2. These proteins were undetectable in replacer-fed gilts. Returning replacer-fed gilts to nursing after PND 2 did not restore cervical expression of these proteins by PND 14. RLX increased (P < 0.05) cervical estrogen receptor-α, vascular endothelial growth factor, and B-cell lymphoma-2 protein in nursed gilts, MMP2 protein in nursed and replacer-fed gilts, and decreased (P < 0.05) pro-MMP9 protein in nursed gilts, and RXFP1 mRNA levels in nursed and replacer-fed gilts at PND 2. Replacer feeding for 2 wk from birth increased (P < 0.05) RXFP1 mRNA levels on PND 14. Results support the lactocrine hypothesis for maternal programming of neonatal tissues. Nursing from birth is required to establish the neonatal cervical developmental program and to maintain cervical developmental trajectory to PND 14.

Nursing for 48 Hours from Birth Supports Porcine Uterine Gland Development and Endometrial Cell Compartment-Specific Gene Expression1

“…Here, results show that imposition of the lactocrine-null state for 2 days from birth, by substituting milk replacer feeding for nursing, changed the uterine developmental program by PND 2 such that the developmental trajectory of the endometrium was altered at histomorphological, cellular, and molecular levels on PND 14. These studies support and extend findings for the cervix [41] by showing that returning colostrum-deprived gilts to nursing after PND 2 fails to rescue uterine endometrial phenotype. Results provide evidence that lactocrine signaling during the first 48 h of neonatal life triggers cell compartmentspecific gene expression events and affects related cell behaviors that drive endometrial morphogenesis.…”

“…Earlier studies indicated that nursing is required for establishment of neonatal porcine uterine [40] and cervical [41] developmental programs between birth and PND 2. Present results confirm and extend those findings.…”

“…Prior to this report, assessment of the effects of nursing on patterns of FRT development involved analysis of gene expression in uterine [40] and cervical [41] tissue extracts. Here, histological, IHC, and LMD technologies were employed to determine effects of nursing on patterns of uterine wall development at histological, cellular, and molecular levels.…”

“…Recent studies of porcine uterine [40] and cervical [41] tissues show that lactocrine signaling is required to support establishment of tissue-specific neonatal developmental programs, defined as the sequence of events that ultimately specify cell fate and determine cell and tissue identity and function [41]. In these studies, nursing was shown to support normal expression patterns of key markers and mediators of uterine and cervical development including ESR1, VEGFA, and the RLX receptor, RXFP1.…”

“…In these studies, nursing was shown to support normal expression patterns of key markers and mediators of uterine and cervical development including ESR1, VEGFA, and the RLX receptor, RXFP1. Moreover, data for whole cervical tissue [41] show that disruption of lactocrine signaling for 2 days from birth (Postnatal Day [PND] 0) by milk-replacer feeding induces changes in cervical protein and gene expression patterns at PND 2 that persist to PND 14, even when replacer-fed gilts are returned to nursing at the end of PND 2. Effects include significant down-regulation of ESR1 protein expression.…”