Milk-borne lactocrine-acting factors affect gene expression patterns in the developing neonatal porcine uterus

Abstract

Lactocrine communication of milk-borne bioactive factors (MbFs) from mother to offspring through nursing can affect neonatal development with lasting consequences. Relaxin (RLX), a lactocrine-active peptide found in porcine colostrum, stimulates estrogen receptor-a (ESR1) expression required for uterine development shortly after birth (postnatal dayZPND 0). Whether other MbFs or cooperative lactocrine mechanisms affect the neonatal uterine developmental program is unknown. To determine the effects of age, nursing, and exogenous RLX on gene expression associated with uterine development, gilts (nZ4-5/group) were assigned to nurse ad libitum or to receive milk replacer, with or without exogenous RLX (20 mg/kg BW i.m./6 h for 48 h), from birth to PND 2 when uteri were collected. Body weight and uterine weight increased (P!0.05) similarly from birth to PND 2 in all gilts. However, colostrum consumption was required for normal uterine ESR1, vascular endothelial growth factor (VEGFA), matrix metalloproteinase 9 (MMP9), and RLX receptor (RXFP1) protein and/or transcript expression on PND 2. Uterine ESR1, VEGFA, and MMP9 protein levels were below (P!0.01) the assay sensitivity in replacer-fed gilts. Supplemental RLX increased (P!0.05) uterine ESR1 protein and mRNA in nursed gilts, as well as VEGFA protein in nursed and VEGFA mRNA in both nursed and replacer-fed gilts. RLX treatment did not affect uterine MMP9 mRNA levels. When compared with replacer-fed gilts on PND 2, uterine RXFP1 mRNA was reduced (P!0.05) in nursed gilts and in RLX-supplemented replacer-fed gilts. These results constitute the first evidence that establishment of the neonatal porcine uterine developmental program requires maternal lactocrine support.

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

“…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.…”

“…Given that nursing is required to support the normal course of ESR1 and related gene expression events in the neonatal porcine uterus [40], it is reasonable to suggest that lactocrine signaling should be considered as an element of the organizational palette of factors required to optimize uterine development and tissue developmental trajectory. The extent to which colostrum consumption affects uterine histogenesis and endometrial development has not been described.…”

“…Moreover, lactocrine-sensitive, tissue compartment-specific developmental events [38] associated with programming of endometrial function remain to be defined. Therefore, to extend previous observations on whole uterine tissue [40], this study was conducted to determine effects of nursing for 2 days from birth on 1) endometrial histogenesis, including patterns of cell proliferation and ESR1 expression in situ; and 2) temporospatial patterns of RXFP1, ESR1, and VEGFA expression, using laser microdissection (LMD), at PND 2 and PND 14 in the neonatal pig.…”

Inhibition of epidermal growth factor receptor restores decidualization markers in stromal fibroblasts from women with endometriosis

“…treatment effects were identified by performing a set of preplanned contrasts to include comparisons of specific groups for each target transcript or protein (24). In all cases, significance was set at a p value of <0.05.…”

Isolation and identification of a high molecular weight protein in sow milk

“…However, studies on sow milk proteins are relatively few. In recent years the importance of sow milk proteins has received increasing attention (Hansen et al, 2012;Krogh et al, 2012) and a number of new milk proteins have been reported (Chen et al, 2011). A polymorphic high molecular weight protein (HMWP) in sow milk was reported by Zou et al (1992), Zhang et al (2004) and Zhang et al (2006).…”