Reproductive and Developmental Toxicity of Microcystin-LR in Mammals

Cyanobacterial harmful algal blooms have increased globally, likely in part due to climate change and anthropogenic eutrophication, elevating exposure of humans and other terrestrial and aquatic animals to cyanotoxins through drinking water, food chains, and recreational activities. Microcystin-LR (MC-LR), the most prevalent microcystin congener, is well known for its hepatotoxicity, yet accumulating evidence indicates that it also exerts reproductive and developmental toxicity in mammals. This review summarizes recent experimental and epidemiological studies indicating that MC-LR disrupts reproductive function through direct cellular injury to germ and somatic cells, dysregulation of gonadal steroidogenesis, and impairment of the hypothalamic-pituitary-gonadal (HPG) axis. In males, MC-LR disrupts spermatogenesis and sperm quality, while in females it impairs oocyte competence, uterine receptivity, and placental function, leading to adverse pregnancy outcomes. Importantly, exposure during critical developmental windows can influence developmental trajectories and contribute to long-term, multi-organ dysfunction in offspring via endocrine imbalance and epigenetic reprogramming. Mechanistically, MC-LR toxicity involves convergent oxidative stress, mitochondrial dysfunction, inflammatory signaling, DNA damage, and chromatin remodeling. Collectively, these findings indicate that reproductive and developmental toxicity should be considered in assessments of the health risks associated with MC-LR and support the incorporation of reproductive endpoints into human health and ecological risk assessment frameworks.