CONTEXT: The impact of early life events on testicular function in adulthood is not well understood.

OBJECTIVE: To study the early influences of fetal growth, exposures to cigarette smoke in utero and cord blood estrogens, and the influences of growth and adiposity in childhood through adolescence; on testicular function in adulthood.

DESIGN: Male members of the Western Australian Pregnancy Cohort (Raine) were contacted at 20-22 years of age. Of 913 contacted, 423 (56%) agreed to participate; 404 underwent a testicular ultrasound, 365 provided a semen sample, and reproductive hormones were measured (384). Fetal growth measurements (n = 137), umbilical cord estrogen concentrations (n = 128), cord testosterone (T) (n = 125), and child-adulthood growth charts (n = 395) were available.

RESULTS: Median sperm output for the 18.6% of men exposed in utero to smoking was lower than nonexposed (82.4 × 10(6) vs 123.1 × 10(6); P = .029). Sperm output in adulthood was inversely correlated with cord serum estradiol (P = .019) and estrone (P = .018). The sperm output of men whose cord blood estradiol and estrone were less than 50th percentile vs more than 50th percentile was 191.1 × 10(6) vs 100.5 × 10(6) (P = .002) and 190.0 × 10(6) vs 106.0 × 10(6) (P = .012), respectively. Men with favorable fetal growth patterns in utero were less likely to have total motile sperm counts within the lowest quartile (P = .011), and men born prematurely had reduced serum T levels in adulthood (13.4 vs 16.6nmol/L, P = .024). Consistent height above the 50th percentile for age through childhood was associated with larger adult mean testicular volume (P < .001). Optimal body mass index trajectory through childhood and adolescence was associated with larger testicular volume (P = .009) and higher serum inhibin B (P = .010) and T (P = .003) in adulthood.

CONCLUSIONS: Exposures to maternal smoking and higher cord blood estrogens at delivery were associated with a reduced sperm output in adulthood. Optimal adult testicular function depends on being born at or above average weight, and maintaining optimal growth and adiposity into adulthood.