LACTATION BIOLOGY SYMPOSIUM: Lactocrine signaling and developmental programming1,2

Abstract

Lactocrine signaling is defined as transmission of bioactive factors from mother to offspring as a consequence of nursing. Lactocrine transmission of signaling molecules may be an evolutionarily conserved process through which bioactive factors necessary for support of neonatal development are delivered postnatally. Dependence on maternal resources for development in eutherian mammals extends into neonatal life for at least that period of time when nutrition is obtained solely from first milk (i.e., colostrum). Data for the pig (Sus scrofa domesticus) provide evidence of lactocrine mediated effects on development of the female reproductive tract and other somatic tissues. Porcine uterine gland development, an estrogen receptor-alpha (ESR1)-dependent process, begins within 2 d of birth [postnatal day (PND) 0]. A lactocrine-driven, ESR1-mediated process was proposed as a regulatory mechanism governing onset of uterine gland development and endometrial maturation in the neonatal pig. Gilts maintained in a lactocrine-null state for 2 d from birth by milk-replacer feeding displayed altered patterns of endometrial gene expression and retarded uterine gland development by PND 14. In lactocrine-null gilts, inhibition of endometrial and cervical ESR1 and vascular endothelial growth factor (VEGFA) expression observed on PND 2 persisted to PND 14, even after gilts were returned to nursing on PND 2. Collectively, data support a role for lactocrine signaling in regulation of critical neonatal developmental events. Maternal lactocrine programming of postnatal development may help to insure healthy developmental outcomes. A systems biology approach will be required to define and understand mechanistic dynamics of lactocrine signaling events that may ultimately connect genotype to phenotype and establish the parameters of reproductive potential.

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

“…Undetectable at birth [44], porcine endometrial ESR1 expression was recently documented in both stroma and nascent GE for uterine tissues obtained at 24 h postnatally [7] and is routinely identified by PND 2 [7,40]. These observations were confirmed in the present study.…”

“…Present data indicating increased stromal RXFP1 expression for lactocrine-null gilts on PND 14 are consistent with those observations. Temporospatial patterns of ESR1 expression and ESR1 immunostaining illustrated here and elsewhere [7,44] for neonatal porcine endometrium suggest the evolution of paracrine conditions necessary to support stromal-epithelial interactions regulating endometrial adenogenesis and proliferation of nascent GE [59][60][61]. Results showing that endometrial ESR1 expression is most pronounced in stroma of nursed gilts within 2 days of birth and increases in the epithelial compartment with differentiation of nascent, proliferating, ESR1 þ GE agree with the idea that stromally derived ESR1-mediated signals support epithelial proliferation [60].…”

“…Observations indicating that effects of nursing on neonatal endometrial development can be tissue compartment specific point to the importance of stromalepithelial interactions as determinants of uterine developmental trajectory. Efforts to understand how lactocrine signaling affects establishment of the uterine developmental epigenotype [7] will provide important insights into maternal programming of reproductive performance and health.…”

“…If the lactocrine hypothesis is correct, disruption of lactocrine signaling would be predicted to have long-term consequences for uterine function and fecundity. In a recent report [7], the relationship between PND 0 immunoglobulin immunocrit, a measure of colostrum intake by neonatal piglets [63], and litter size was defined using data for 381 gilts over four parities (approximately 1525 litters). As predicted by the lactocrine hypothesis, results showed that low immunocrit, indicative of minimal colostrum consumption on PND 0, was associated significantly with reduced litter size in adulthood.…”

“…Thus, nursing facilitates the fetal to neonatal transition and provides a mechanism for maternal and related environmental factors to affect neonatal growth and developmental programming [1][2][3][4][5][6][7][8]. The conserved nature of lactation [2,3] suggests that transmission of nutrients and milk-borne bioactive factors (MbFs) from mother to offspring as a consequence of nursing has provided important adaptive advantages to mammals through lactocrine regulation [7,9,10] of critical developmental events during neonatal life. Although lactation strategies vary widely among mammals, milk consumption has broad implications for development that extend beyond basic nutritional support [2,11,12].…”