Embryonic exposure to aluminium chloride blocks the onset of spermatogenesis through disturbing the dynamics of testicular tight junctions via upregulating Slc25a5 in offspring
Studies reveal neurotoxicity, hepatotoxicity, and developmental and reproductive toxicity in mice exposed to aluminium (Al). However, relatively few researches are conducted to clarify the mechanism of the impact of embryonic exposure to aluminium chloride (AlCl3) on the development of the reproductive system in male offspring. Here, pregnant mice were fed AlCl3 by gavage from day 12.5 of gestation. The results showed that embryonic AlCl3 exposure disrupted testicular development and spermatogenesis by damaging the testicular structure, reducing sperm counts, and altering the expression of the tight junction (TJ) proteins between Sertoli cells (SCs). Further in vitro studies showed that AlCl3 treatment stabilized the TJ proteins Occludin and ZO-1 expression by inhibiting the ERK signaling pathway to upregulate the Slc25a5 protein, which prompted ATP production to disrupt cytoskeletal protein homeostasis. Therefore, our study provided a new mechanism for AlCl3 exposure to interfere with testicular development and spermatogenesis and implied that Slc25a5 could be a target of AlCl3 affecting cell metabolism. Overall design: TM4 cells were incubated with AlCl3 for 30 days.The mRNAs were then validated by qPCR at the animal level, finally screening out the differentially expressed target gene Slc25a5.