Alzheimer's disease-related amyloid-β_1-42 peptide induces the loss of human sperm function

Characteristically identified as the main component of senile plaques present in patients suffering from Alzheimer's disease, Aβ has been detected in human testis and reproductive fluids, but its effect on spermatozoa has not been addressed. The present study evaluated whether the most toxic and aggregant amyloid precursor protein (APP)-proteolytic product, amyloid-β_1-42 (Aβ_1-42), was capable of affecting sperm functionality. Normozoospermic samples were either exposed to different Aβ_1-42 doses or to the untreated and scrambled controls for a maximum of 48 h at 37 °C and 5%CO₂, and motility, viability and mitochondrial status were evaluated. Additionally, tyrosine phosphorylation was analyzed by immunocytochemistry and acrosomal integrity through PSA-FITC. A shorter treatment period was used to monitor prompt Ca²⁺ responses. Aβ_1-42 peptide decreased motility before inducing mitochondrial impairment (p < 0.05; n = 6). Both outcomes became more pronounced with time, reaching their maximal decrease at 48 h, where even 1 μM produced undesirable effects (p < 0.05; n = 6). Aβ_1-42 peptide also decreased cell survival (p < 0.05; n = 6). Furthermore, although no effects on tyrosine phosphorylation were observed (p > 0.05; n = 6), reduced acrosomal integrity was detected (p < 0.05; n = 7), which was not correlated with viability loss (p > 0.05). In parallel, all Aβ_1-42 concentrations elicited a [Ca²⁺]_i rise but a significant difference was only observed at 20 μM (p < 0.05; n = 7) and a tendency was obtained with 10 μM (p = 0.053; n = 7). In conclusion, Aβ_1-42 peptide oligomers impair sperm function in vitro, although further studies are required to determine the clinical relevance of these findings.