227 Lactocrine programming enhances testicular growth and alters the testicular proteome in the neonatal boar.

Abstract Boar fertility is critical for swine reproductive efficiency. Sperm production capacity is driven by Sertoli cell numbers within the testis. Sertoli cell proliferation is malleable in early life but ceases post-puberty. Extensive Sertoli cell proliferation occurs in neonates, a period termed mini-puberty that overlaps temporally with nursing. Previous data demonstrates that colostrum consumption promotes neonatal Sertoli cell proliferation and subsequent sperm production in the boar, a phenomenon termed lactocrine programming. For example, boars who consumed more colostrum as neonates produced 17 billion more sperm per ejaculate (15% increase) compared to boars with lower colostrum intake. However, the biological mechanisms underlying this effect are unclear. The objective of this study was to determine how consumption of sow milk affects testicular development and reproductive endocrinology in neonatal pigs. After birth, white crossbred neonatal boars nursed colostrum ad libitum for 2 days prior to treatment. Boars were randomly assigned to consume either sow milk (n = 4) or milk replacer (n = 4; NutraStart Liqui-Wean) three times daily (90 ml/feeding) for eight days. At 10 days of age, boars were weighed and euthanized prior to testis and blood collection. Testes were weighed and snap frozen for subsequent proteomics. Serum concentrations of thyroxine (T4), gonadal steroids (Leydig cell products), and anti-müllerian hormone (AMH; Sertoli cell product) were quantified. Milk-fed boars had 35% heavier testes (P = 0.031) compared with replacer-fed pigs, despite no difference in body weight (P > 0.05). Serum concentrations of T4 were 30% greater in milk-fed boars compared with replacer-fed animals (P = 0.0339). Circulating concentrations of AMH and gonadal steroids (e.g., testosterone, 17β-estradiol) did not differ between treatments (P > 0.05). Regarding testicular proteomics, a total of 1,517 proteins were detected. Of these, 49 proteins were upregulated and 721 proteins were downregulated within the testes of milk-fed boars compared to replacer-fed (P < 0.05). Downregulated proteins within testes of milk-fed boars included those important for germ cell differentiation (e.g., DDX4), steroidogenesis (e.g., HSD3B), and apoptosis (e.g., PDCD4). In addition, AMH was also downregulated within testes of milk-fed boars, indicating an effect on Sertoli cells. Upregulated testicular proteins included mediators of cellular metabolism (e.g., IDH1), steroidogenesis (e.g., StAR), cell proliferation (e.g., CHD5), and antioxidant defenses (e.g., GSTO1). Notably, INSL3 – a biomarker of Leydig cell functionality – was also upregulated within milk-fed versus replacer-fed testes. Interestingly, transthyretin (thyroid hormone transporter) was also elevated, consistent with increased circulating T4 concentrations in milk-fed boars. To conclude, these data elucidate the biological mechanisms underlying lactocrine programming of the porcine testis. Neonatal intake of sow milk increased testicular weight, indicative of a proliferative effect on Sertoli cells. Therefore, manipulation of neonatal diet may be a novel intervention to develop boars with greater reproductive potential.