Nutritional and immunological benefits of colostrum (herein referred to as milk) for neonatal growth and survival are well known. However, the role of milk as a conduit for bioactive factors that can affect neonatal development is not well understood. Immunoreactive relaxin (RLX) was detected in porcine milk and in the systemic circulation of newborn pigs only if they were allowed to nurse. In addition, the neonatal cervix is sensitive to trophic effects of RLX by postnatal day (PND) 2. Thus, the lactocrine hypothesis was proposed as a mechanism whereby milk-borne growth factors are delivered to nursing offspring where they can affect target tissues. Whether milk and/or RLX are necessary for neonatal porcine cervical development is unknown. Here, objectives were to determine effects of: 1) age and consumption of milk on expression of molecular markers of cervical growth, remodeling and apoptosis at birth (PND 0; before nursing) and on PND 2; and 2) exogenous RLX on cervical expression of targeted markers in gilts allowed to nurse versus those fed hormone-free milk replacer. Targeted proteins included estrogen receptor-alpha (ESR1) and vascular endothelial growth factor (VEGFA), both mediators of porcine cervical growth, matrix metalloproteinase 2 (MMP2), involved in tissue remodeling, and the anti- and pro-apoptotic markers BCL2 and caspase 3. Gilts (n = 4-7/group) were assigned randomly to one of four treatment groups at birth, in which they were: 1) allowed to nurse ad libitum; 2) fed milk replacer; 3) nursed and given either RLX (20 µg/kg BW, im) or vehicle every 6 h for 48 h; or 4) fed replacer and treated with exogenous RLX/vehicle for the first 48 h of life. Cervices were collected on PND 2, approximately 3 h after the last treatment. Additionally, cervices were collected from a fifth group at birth, before gilts were allowed to nurse. Protein expression was evaluated by immunoblotting and quantified by densitometry. Expression of cervical ESR1, VEGFA and BCL2 proteins, undetectable at PND 0, was induced in gilts allowed to nurse for two days, but remained undetectable in replacer-fed gilts. In contrast, MMP2 expression, also undetectable at PND 0, was induced in both nursing and replacer-fed gilts. RLX increased ESR1, VEGFA and BCL2 expression in nursing (p < 0.05) but not in replacer-fed gilts. MMP2 expression was increased by RLX treatment in both nursing and replacer groups (p < 0.01). Caspase 3 expression was undetectable at both PND 0 and 2, regardless of treatment. Data support the lactocrine hypothesis for maternal programming of neonatal development, showing that milk-borne factors are important for induction of growth and anti-apoptotic proteins in the cervix at PND 2. Data support the idea that lactocrine-acting factors may be cooperative in facilitating the actions of RLX. In the absence of milk, altered expression patterns for morphoregulatory proteins, as observed here, could affect neonatal cervical development with long-term consequences for reproductive performance and health. Data complement earlier results indicating that the neonatal porcine cervix is sensitive to RLX as reflected by increased expression of specific growth, remodeling and anti-apoptotic proteins. Thus, lactocrine-driven programming must be considered a potentially critical component of the maternal continuum of factors affecting female reproductive tract development. (Support: USDA-NRI 2003-35203-1357 and 2007-35203-18098; NSF-EPS 0814103) (poster)