AIMS: Artificial light exposure at night and irregular light schedules are increasingly prevalent environmental stressors in modern society and have been implicated in male reproductive disorders. This study aimed to determine how distinct patterns of circadian rhythm disruption differentially affect male reproductive function and to elucidate the underlying mechanisms.
MATERIALS AND METHODS: Three groups of male rats were subjected to standard 12-h light/12-h dark cycles (LD), fixed inverted light-dark cycles (DL), and a dynamic alternating light-dark-dark-light cycle (LDDL) designed to induce circadian rhythm instability. Reproductive outcomes including body weight, testicular index, serum testosterone levels, and sperm parameters were assessed. Testicular oxidative status was evaluated by measuring NOX4/5, HO-1, SOD, and MDA levels, while apoptosis was examined using Bax/Bcl-2 ratio, cleaved caspase-3 expression, and TUNEL staining.
KEY FINDINGS: Male rats exposed to the LDDL cycle exhibited significant reproductive dysfunction, manifested as markedly reduced testicular index, decreased serum testosterone concentration, and impaired sperm motility. Mechanistically, LDDL conditions enhanced testicular oxidative stress, manifested by NOX4/5 upregulation and HO-1/SOD suppression. This redox imbalance was accompanied by germ cell apoptosis activation, evidenced by elevated Bax/Bcl-2 ratios, increased cleaved caspase-3 expression, and a higher proportion of TUNEL-positive cells. Notably, reproductive damage was more pronounced under dynamic circadian rhythm disruption than under fixed light-dark reversal conditions.
SIGNIFICANCE: By linking dynamically light-induced circadian disruption to testicular oxidative stress and apoptotic signaling pathways, it elucidates potential mechanisms by which modern lighting environments impair male fertility and provides strategies for circadian rhythm intervention and environmental mitigation.
