Fetal Origin Programming of the Male Reproductive System

Abstract

The Developmental Origin of Health and Disease (DOHaD) theory, in which the prenatal environment is involved in the development of diseases after birth, has been widely accepted. This theory is widely accepted, and the involvement of the prenatal environment in the development of adult diseases (lifestyle diseases) is almost certain. As an extension of the DOHaD theory, the Testicular Dysgenesis Syndrome (TDS) hypothesis, which focuses specifically on diseases of the male reproductive system, proposes that environmental changes during the embryonic period are involved in the development of a number of diseases of the male reproductive system, such as hypospadias, cryptorchidism, low sperm count, and infertility. A few experimental studies were performed; however, the results have been limited and have not addressed the pathogenic mechanism of TDS. We have conducted research using a mouse model of maternal nutritional deprivation. In this study, under/hyponutrition during fetal life impairs testosterone production in the fetal testis and causes a decrease in sperm count after growth. Further studies elucidated that this may be due to oxidative stress-induced germ cell apoptosis caused by fetal testosterone depletion. The molecular biological background to the DOHaD theory is epigenetic modification, but very few studies have focused on epigenetic modification in TDS, which shares the same background as the DOHaD phenomenon. We will further discuss the contribution of epigenomic modifications in the development of TDS.