Elevated body mass index in and infections in early adolescence may impair Leydig cell development and reduce androgenic potential in adulthood.
"The steroidogenic Leydig cells of the testes are unusual in that once they are established in young adulthood this population of cells remains relatively stable without further cell division for the remainder of the male lifespan, and with only minimal cell attrition," noted Richard Ivell (School of Biosciences, University of Nottingham, UK) and colleagues.
Early-life determinants of Leydig cell functional capacity in young men were examined using circulating insulin-like peptide 3 (INSL3) as a biomarker. INSL3 is a constitutively secreted hormone from mature Leydig cells that remains stable, but varies significantly between individuals and serves as a proxy for androgen-producing potential. Utilizing the Avon Longitudinal Study of Parents and Children, the team assessed associations between maternal, neonatal, childhood, and adolescent factors and INSL3 levels at 17 and 24 years of age.
The cohort included 1,781 male participants with available blood samples at both time points. INSL3 was measured using a time-resolved fluorescent immunoassay. Anthropometric, lifestyle, and infectious disease data were gathered through direct assessments and structured questionnaires, and statistical analyses included bivariate correlations, t-tests, and multiple regression models.
Maternal parameters—including smoking status, birth weight, gestational age, and being small for gestational age—were not associated with INSL3 concentrations at age 24.
Conversely, childhood body mass index (BMI) showed consistent inverse associations. At 13 years of age, being overweight (BMI > 85th percentile) was associated with significantly lower INSL3 levels at 24 years, indicating a 20% reduction. These negative associations were also observed at 9 and 17 years.
Early childhood infection, particularly chickenpox before 30 months of age, was linked to significantly reduced INSL3 concentrations. At 24 years, those with early chickenpox exhibited INSL3 levels at a 13% decrease. Other infections such as whooping cough and mumps demonstrated similar trends but were limited by small sample sizes.
"These results strongly support the use of appropriate vaccination in young children now additionally to alleviate a possible risk of later reduced androgen production," said Ivell and colleagues.
Further studies are needed to validate the associations and explore underlying mechanisms.
The researchers reported no commercial or financial conflicts of interest related to this study.
Source: Andrology