162. Lactocrine Programming of Neonatal Testis Development: Evidence from Swine.

Abstract

The boar has a disproportionately high impact on swine reproductive efficiency and genetic progress; therefore, developing fertile sires is critical for efficient pork production. Extensive testis development occurs during neonatal life, a highly plastic period that overlaps temporally with nursing. Previous studies from multiple groups have demonstrated that nursing supports postnatal testis development and function in boars. For example, colostrum intake enhanced Sertoli cell proliferation by 34% within 48 h of life versus those fed milk-replacer. In addition, high neonatal colostrum intake [as indicated by the immunoglobulin immunocrit assay (iCrit)] was strongly correlated with total sperm per ejaculate in adulthood (r = 0.8539), such that high-iCrit boars produced ∼17 billion more sperm per ejaculate (15% increase) than low-iCrit boars. Moreover, boars raised in small litters with greater colostrum/milk access produced 27% more sperm in adulthood than those raised in large litters. These results align with the “Lactocrine Hypothesis,” which states that bioactive factors in maternal milk program postnatal development in offspring. Extensive evidence demonstrates that relaxin in sow milk drives lactocrine programming of uterine gland development in gilts, but comparable mechanistic data are lacking for boars. Recent studies from our group have sought to address this gap in knowledge. Collaborative studies with investigators at USDA-ARS, Auburn University, and Rutgers University recently demonstrated that iCrit status (high versus low) altered the neonatal testicular proteome in boars, including proteins related to Leydig and germ cell function. Notably, high-iCrit boars had more germ cells within the testis than weight-matched littermate low-iCrit boars. In a separate study, we investigated how neonatal consumption of mature sow milk (versus colostrum) influenced early testis development. Neonatal intake of mature sow milk over 8 days altered the testicular proteome, increased hormone production, and increased testicular weight compared with milk-replacer–fed littermate piglets. Because Sertoli cell number determines testis size, these results suggest that sow milk consumption enhanced Sertoli cell proliferation in early life. These effects may be directly mediated by extracellular vesicles (EVs) in sow milk. In another study, consumption of milk replacer with and without sow milk EVs acutely altered the neonatal testicular proteome and reproductive hormone production. Using transgenic swine that produce milk EVs endogenously labeled with the green fluorescent protein ZsGreen1, we determined that milk EVs survive digestion, cross the intestinal mucosa, enter neonatal circulation, and traffic to the testes in vivo. Collectively, these findings support the lactocrine hypothesis and provide new mechanistic insight into how maternal milk and colostrum program reproductive development in boars. Furthermore, these findings have implications for other livestock species with limited maternal milk consumption (e.g., dairy cattle).