Chronic stress is a crucial public issue that occurs when a person
is repetitively stimulated by various stressors. Previous
researches have reported that chronic stress induces
spermatogenesis dysfunction in the reproductive system, but its
molecular mechanisms remain unclear. The nectin protein family,
including nectin-1 to nectin-4, is Ca2+-independent
immunoglobulin-like cell adhesion molecules, that are widely
expressed in the hippocampus, testicular tissue, epithelial cells
and other sites. Nectin-3 contributes to the sperm development
at the late stage, and the abnormal expression of nectin-3
impairs spermatogenesis. Some recent studies have
demonstrated that stress induces a decrease in nectin-3
expression in the hippocampus via corticotropin-releasing
hormone (CRH) to corticotropin-releasing hormone receptor 1
(CRHR1) pathway. Here, we tested whether chronic stress also
caused a reduction in nectin-3 expression in the testis. We
established a chronic social defeat stress paradigm, which
provides naturalistic and complex chronic stress in male C57BL/6
mice. After 25 days of chronic social defeat stress, the mice
showed weight loss, thymic atrophy and some other typical
symptoms of chronic stress (e.g. anxiety-like behavior and social
avoidance behavior). We found gonad atrophy, testicular
histological structure changes and semen quality reductions in
the stressed mice. The stressed male mice significantly spent
more time to impregnate the female mice than the control male
mice. Moreover, nectin-3 protein levels in stressed mice were
significantly decreased in the testes compared with those in
control mice. In addition, we found that the CRHR1 expression
level was increased in the testes of stressed mice. Therefore, we
demonstrated a decreased level of nectin-3 expression and
an increase in CRHR1 expression in the testis after exposure to
chronic stress, which may provide a potential therapeutic target
for the spermatogenesis dysfunction induced by chronic stress.