Milk-Borne Relaxin and the Lactocrine Hypothesis for Maternal Programming of Neonatal Tissues

The fact that all newborn mammals drink milk extends the time frame of maternal influence on development into neonatal life. While the nutritional and immunological benefits of milk are clear, the role of milk as a conduit for bioactive factors with the potential to affect neonatal development is less well defined. Porcine and canine milk contain immunoreactive relaxin (RLX) that is transmitted into the circulation of nursing offspring. In the pig, a window of opportunity for transmission of milk‐borne RLX is open at birth and remains so for about the first 3 days of neonatal life. Recent studies have shown that pro RLX is the major form of RLX in milk and that milk‐borne porcine pro RLX is biologically active. Moreover, RLX receptor (RXFP1) expression is detectable in the porcine female reproductive tract and other somatic tissues at birth. The lactocrine hypothesis for maternal programming of neonatal development was proposed as a mechanism whereby RLX, a prototypical milk‐borne growth factor in the pig, is delivered to nursing offspring, where it can affect development of RXFP1‐positive target tissues. Data indicating that treatment of newborn gilts with RLX increased estrogen receptor‐α expression in the uterus and cervix by postnatal day 2 support a role for RLX in lactocrine programming of the female reproductive tract. Effects of RLX on Wnt/β‐catenin expression in neonatal porcine cardiac tissue support a role for RLX in developmental programming of nonreproductive target tissues as well. Ongoing studies will test the lactocrine hypothesis for maternal programming of development by RLX and related milk‐borne factors.