Testicular Vulnerability to Early-life Stress and High-fat Diet

The sustained decline in fertility rates and the rising prevalence of male infertility have increased interest in understanding how environmental and biological factors act across development to shape reproductive function.Among these factors, early-life stress induced by maternal separation and high-fat diets represent two highly relevant conditions capable of persistently altering endocrine, metabolic, and testicular physiology.Evidence in humans indicates that adverse childhood experiences are associated with disruptions in the hypothalamic-pituitary-gonadal (HPG) axis, reduced semen quality, and altered pubertal timing.Complementarily, overweight and high intake of saturated fats are linked to oxidative stress, sperm DNA damage, and impaired spermatogenesis.Experimental models of maternal separation and high-fat diet exposure in rodents have helped elucidate underlying cellular and tissue mechanisms, including reduced numbers of sustentacular cells, disorganization of the germinal epithelium, disruption of the blood-testis barrier, decreased testosterone levels, and the establishment of a pro-inflammatory testicular microenvironment.Although both factors have been extensively studied independently, their interaction remains an emerging field.Early adversity increases metabolic vulnerability and preference for fat-rich foods, suggesting that their combined exposure may produce cumulative deterioration of testicular morphofunction.This manuscript critically reviews the available evidence and highlights the need for integrated experimental designs that simultaneously examine the impact of postnatal stress and nutrition on testicular maturation and fertility, providing a more comprehensive perspective for understanding male reproductive programming within the Developmental Origins of Health and Disease framework.