Fetal Origin of Testicular Dysplasia

Testicular dysplasia is a condition characterized by testicular volume reduction, dysfunction of testosterone synthesis, and decreased sperm quality. Both clinical and basic studies have demonstrated that testicular dysplasia has a fetal origin. Exposure to adverse environments during pregnancy, such as exogenous substances and poor maternal health, can result in abnormal morphological and functional development of the fetal testicle. This, in turn, can lead to changes in the developmental programming of the hypothalamic-pituitary-testicular axis after birth. The underlying mechanisms include abnormal secretion of local factors, such as insulin-like growth factor 1, changes in intrauterine neuroendocrine metabolic programming, oxidative stress, mitochondrial damage, and abnormal epigenetic modifications, such as DNA methylation, histone modification, and regulation of noncoding RNA. Furthermore, epigenetic modifications of key genes can evade germ cell reprogramming and be passed on to subsequent generations, resulting in multigenerational inheritance effects of testicular dysplasia. This chapter provides a comprehensive review of the evidence supporting the fetal origin of testicular dysplasia and its intrauterine programming mechanisms. The findings have significant implications for guiding eugenics and improving the quality of the population.