The early days of life represent an important period for neonatal uterine development in the pig. The porcine uterus develops in utero and continues postnatally. Events during neonatal life that establish uterine histoarchitecture contribute to the developmental program of the uterus and set the trajectory for adult uterine phenotype. Uterine programming is sensitive to hormonal perturbations. Exposure to bioactive factors during neonatal life influences uterine maturation with long-term consequences for reproductive performance. The goal of this research was to study factors in the neonatal environment that alter uterine developmental gene expression. These include mediators of growth [estrogen receptor alpha (ESR1), vascular endothelial growth factor (VEGFA) and relaxin receptor (RXFP1)], patterning (WNT7A and HOXA10) and remodeling [matrix metalloproteinase (MMP)9 and 2]. Results indicated that exposure to estradiol valerate (EV) from birth (postnatal day [PND] 0) to PND 14 increased uterine ESR1 and VEGFA protein, along with HOXA10, RXFP1 and MMP9 transcripts and decreased WNT7A transcripts, in PND 14 neonates. Endometrial gene expression changes also occured in adulthood on day 12 of pregnancy as a consequence of neonatal EV exposure. This included decreases in WNT7A and MMP9 transcripts, ESR1 and VEGFA protein and reduced MMP9 activity. Next, exposing gilts perinatally to the estrogenic mycotoxin zearalenone (ZEA), decreased uterine ESR1, WNT7A and RXFP1 mRNA levels on PND 21 compared to unexposed gilts. Extending the concept that postnatal uterine development in gilts can be influenced by maternally-derived signals, studies showed that nursing from birth supported uterine ESR1, VEGFA and MMP9 protein expression at PND 2 and PND 14 in comparison to milk replacer-fed gilts. Treatment with relaxin, an uterotrophic milk-borne hormone, did not restore the uterine phenotype of replacer-fed animals to that of nursing gilts at PND 2, although it did predictably affect RXFP1 transcript levels. Results support the idea that nursing during a critical two-day period from birth supports the neonatal porcine uterine developmental program. Identification of mediators that regulate neonatal uterine programming, the time frame for this regulation and understanding how those mediators are influenced by environmental/lactocrine factors provide critical insights into the mechanisms that govern neonatal tissue development.