Lipophilic phthalic acid esters impair human sperm acrosomal reaction through the likely inhibition of phospholipase A

Phthalic acid esters (PAEs) are recognized endocrine disruptors. Detection of PAEs in semen from idiopathic infertile males suggests possible direct mechanisms of sperm toxicity. In this study we aimed to correlate sperm function with semen levels of PAEs. Semen samples were obtained from 100 male patients attending the Unit of Andrology and Reproductive Medicine, University Hospital of Padova, (Italy), 22 of which having a recognized history of idiopathic infertility. Compared to fertile subjects, infertile patients showed reduced levels of acrosome reaction (AR), evaluated by CD46 staining upon progesterone (P4) triggering (p < 0.001). Subjects showing positive detection of PAEs in semen, evaluated by liquid chromatography-mass spectrometry (LC-MS), were significantly more represented in those reporting an history of infertility (13 out of 22), compared to fertile subjects (25 out of 78, P = 0.0266). In vitro sperm exposure to PAEs showed that lipophilic PAE representative Di-n-octyl phthalate (DNOP) had higher cell accumulation and inhibition of P4-induced AR than less lipophilic PAE representative Dibutyl phthalate (DBP). Computer-based binding analysis and fluorimetric inhibition assay, showed that both DNOP and DBP had similar Phospholipase-A2 (PLA

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.