Postnatal reproductive development and the lactocrine hypothesis

Abstract Text: Maternal contributions to development begin at conception.  Prenatal conditions that evolve in utero through the course of gestation define the environment in which embryogenesis and fetoplacental development occur.  Genotype notwithstanding, maternal effects on development from the time of conception can program cell fate and dictate offspring phenotype as defined by various aspects of performance and health, including fertility and fecundity.  Maternal effects on development do not end at birth, but extend into postnatal life through signals communicated from mother to offspring in first milk (colostrum).  Transmission of bioactive factors from mother to offspring as a specific consequence of nursing defines a lactocrine mechanism.  The female reproductive tract (FRT) is not fully formed at birth. Data for both ungulate species and mice indicate that disruption of the developmental program during critical organizational periods of neonatal life can have lasting effects on the form and function of FRT tissues, including the uterus. Radial patterning of the uterine wall, reflected by differentiation and proliferation of nascent endometrial glands, is a postnatal event in most mammals. Both uterine growth and histogenesis proceed in an ovary-independent manner shortly after birth, suggesting that extra-ovarian inputs are important in this process. Data for the pig indicate that lactocrine signals constitute one source of such uterotrophic support.  Disruption of lactocrine signaling by feeding gilts porcine milk replacer instead of colostrum for two days from birth (postnatal day = PND 0) retarded uterine gland genesis by PND 14.  Differences in endometrial and whole uterine gene expression patterns between colostrum- and replacer-fed gilts were evident by PND 2, when RNA sequencing revealed over 800 differentially expressed, lactocrine-sensitive genes.  Organizationally relevant, lactocrine-sensitive processes, pathways and networks identified through transcriptomic studies included cell adhesion, cell-cell signaling, cytokine-receptor interactions, integrin cell surface interactions, ESR1 and Hedgehog signaling, and the plasminogen activating network. Lactocrine-sensitive expression of nine microRNAs with 115 potential mRNA targets was also identified.  Results provide evidence of lactocrine-mediated, epigenetic effects on multiple elements of the uterine developmental program.  A single oral dose of colostrum given at birth affects endometrial cell behaviors associated with uterine wall development by 12h postnatal.   Evidence that minimal colostrum consumption at birth is associated with reduced lifetime fecundity in adult sows indicates that lactocrine programming can affect reproductive efficiency.  Data support a role for lactocrine signaling in regulation of postnatal reproductive tract development and function.

Keywords: development, lactocrine programming, reproductive tract, uterus