Epigenetic Programming of Porcine Endometrial Function and the Lactocrine Hypothesis

Abstract

Epigenetic programs controlling development of the female reproductive tract (FRT) are influenced by the effects of naturally occurring bioactive agents on patterns of gene expression in FRT tissues during organizationally critical periods of foetal and perinatal life. Aberrations in such important cellular and molecular events, as may occur with exposure to natural or manmade steroid or peptide receptor-modulating agents, disrupt the developmental program and can change the developmental trajectory of FRT tissues, including the endometrium, with lasting consequences. In the pig, as in other mammals, maternal programming of FRT development begins pre-natally and is completed post-natally, when maternal effects on development can be communicated via signals transmitted in milk. Studies involving relaxin (RLX), a prototypic milk-borne morphoregulatory factor (MbF), serve as the basis for ongoing efforts to identify maternal programming events that affect uterine and cervical tissues in the neonatal pig. Data support the lactocrine hypothesis for delivery of MbFs to neonates as a specific consequence of nursing. Components of a maternally driven lactocrine mechanism for RLX-mediated signalling in neonatal FRT tissues, including evidence that milk-borne RLX is delivered into the neonatal circulation where it can act on RLX receptor (RXFP1)-positive neonatal tissues to affect their development, are in place in the pig. The fact that all newborn mammals drink milk extends the timeframe of maternal influence on neonatal development across many species. Thus, lactocrine transmission of milk-borne developmental signals is an element of the maternal epigenetic programming equation that deserves further study.

Nutritional plane and selenium supply during gestation affect yield and nutrient composition of colostrum and milk in primiparous ewes1

“…Additionally, recent research has yielded the lactocrine hypothesis, stating that specific factors in colostrum and milk, such as relaxin, program development of the uterus in pigs (Bartol et al, 2008). Thus growth factors, hormones, and other compounds in colostrum and milk not measured in the present study may be altered due to gestational nutrition and may continue to affect development of important tissues such as the female reproductive tract in offspring, which may contribute to later differences in reproductive performance (Martin et al, 2007).…”

Effects of age, nursing, and oral IGF1 supplementation on neonatal porcine cervical development

“…Nursing supports development of the neonatal porcine reproductive tract by delivering milkborne bioactive factors (MbFs) from mother to offspring as proposed in the lactocrine hypothesis (Yan et al 2006, Bartol et al 2008. In the neonatal pig, lactocrine signaling is important for uterine ) and testicular (Rahman et al 2014) development.…”

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

“…Relaxin (RLX), a prototypical milk-borne bioactive factor (MbF; Bartol et al 2008, Frankshun et al 2009), increases porcine uterine growth (Sherwood 2004, Yan et al 2006a) and stimulates uterine matrix metalloproteinase 2 (MMP2) and MMP9 production and activity important for connective tissue remodeling (Lenhart et al 2001). Administered from birth, exogenous RLX increased uterine weight and both ESR1 and vascular endothelial growth factor (VEGFA) expression in neonatal gilts (Yan et al 2008).…”