Exposure to phthalate esters induces an autophagic response in male germ cells

Abstract

Phthalate esters are plasticizers that impart flexibility to polvinylchloride plastics. As they are not covalently bound, they can leach from a wide range of products, including food containers, medical devices, clothing, and toys, leading to widespread environmental exposure. Phthalate toxicity has been linked to male infertility by disrupting testosterone production and testis development. Phthalates also impair proliferation and viability of spermatogonial stem cells (SSC), the role of which is to support lifelong spermatogenesis. To elucidate cellular mechanisms in spermatogonia affected by long-term phthalate exposure, we grafted primate testis tissue into mice. Grafts treated with di-n-butyl phthalate showed an increase in autophagy compared to controls. Short term in vitro exposure of porcine germ cells to mono(2-ethylhexyl) phthalate, also resulted in an increase in autophagy. Viability was lower in cells exposed to phthalates, but treatment with rapamycin to induce autophagy significantly increased viability. The data suggests autophagy is triggered in spermatogonia as a response to a toxic insult, which may constitute a survival mechanism in spermatogonia.