Adolescent psychological stress impairs spermatogenesis by disrupting meiotic progression in male mice

Psychological stress is a risk factor for male infertility, and adolescence is a critical period of vulnerability to stress. However, the effects of psychological stress on spermatogenesis in adolescent males remain unclear. To investigate this, we used a restraint stress model in adolescent Kunming mice, where animals were restrained for 2 and 4 h per day from postnatal day 28 to 56. Restraint stress resulted in a decreased sperm concentration and serum testosterone levels, together with increased sperm abnormalities, synaptonemal complex protein3 (SYCP3)-positive germ cells in the epididymis, and serum corticosterone levels in adult mice. Additionally, restraint stress altered seminiferous tubule histoarchitecture and the distribution of spermatogenic stages. Restraint-stressed mice exhibited increased proportions of zygotene- and pachytene-stage spermatocytes and a reduced proportion of diplotene-stage spermatocytes. Further analysis showed altered γH2AX and ataxia-telangiectasia and rad3-related (ATR) localization patterns together with increased frequencies of chromosomal synapsis abnormalities and abnormal chiasma formation, which were accompanied by increased spermatocyte apoptosis. The mRNA expression levels of key meiotic genes, including SPO11 initiator of meiotic double stranded breaks (SPO11), DNA meiotic recombinase 1 (DMC1), synaptonemal complex protein1 (SYCP1) and SYCP3, were reduced in stressed mice. In addition, restraint stress increased germ cell apoptosis and reduced litter size in adulthood. In conclusion, adolescent exposure to psychological stressors such as restraint stress is associated with impaired spermatogenesis and reduced reproductive capacity in adult male mice.