Chronic circadian desynchrony disrupts stage-specific spermiogenesis and male fertility

Abstract Circadian disruption is increasingly associated with male reproductive dysfunction, yet the developmental stages underlying this relationship remain poorly defined. We investigated whether chronic circadian desynchrony disrupts the stage-specific molecular and bioenergetic organization of spermiogenesis and compromises male fertility. Adult Wistar rats were maintained under a standard light-dark cycle or exposed for two months to repeated cycles of constant light, constant darkness, and light-dark conditions. Round spermatids, elongated spermatids, and epididymal spermatozoa were analyzed for clock and mitochondria-related gene expression and mitochondrial bioenergetics. Under control conditions, spermiogenesis exhibited coordinated stage- and time-dependent transcriptional and bioenergetic organization, with developing spermatids relying predominantly on oxidative phosphorylation. Circadian desynchrony reduced circulating testosterone and the abundance of elongated spermatids and disturbed stage-specific clock and mitochondrial gene expression, with the most pronounced transcriptional alterations in elongated spermatids. Bioenergetic responses were also stage dependent: ATP production increased in round spermatids but decreased in elongated spermatids and spermatozoa, accompanied by altered mitochondrial homeostasis. Circadian desynchrony also impaired progesterone-induced acrosome reaction and reduced reproductive success. These findings identify spermiogenesis as a circadian-sensitive developmental process and highlight elongated spermatids as a particularly vulnerable stage linking disrupted temporal organization and mitochondrial dysfunction to impaired male fertility.