Tri-ortho-cresyl phosphate (TOCP) has been widely used as plasticizers, and reported causing reproductive toxicity in mammals. However, little is known about the toxic effect on the placenta. In this study, dams were orally administered different doses of TOCP to explore the effect of TOCP on placental development. Results showed that TOCP exposure significantly reduced numbers of implanted embryo, caused atrophy and collapse of ectoplacental cone, and decreased total areas of placenta and numbers of PCNA-positive cells. Expression levels of placental development genes were prominently downregulated in the TOCP-treated groups. Moreover, TOCP administration induced placental apoptosis and autophagy by upregulating P53, Bax, Beclin-1, ratio of LC3 II/LC3 I and Atg5 and downregulating Bcl-2 protein.In addition, TOCP exposure markedly inhibited activities of catalase and superoxide dismutase and increased the production of H 2 O 2 and malondialdehyde. Collectively, these findings suggest that apoptosis, autophagy and oxidative stress may be involved in the TOCP-induced reproductive toxicity. K E Y W O R D S apoptosis, autophagy, oxidative stress, placenta, toxicity, tri-ortho-cresyl phosphate 1 | INTRODUCTION Tri-ortho-cresyl phosphate (TOCP) is the important one of three isomer of tricresyl phosphate (including o-, m-, and p-cresyl). 1 As a plasticizer and organophosphates (OPs) compound, it is widely used in plastics, paint, flame retardant, gasoline additives, solvents, lubricants, and so on. 2,3 In 1930, lots of cases of paralysis were reported in the United States of America due to eating the extract of Jamaica ("jake") contaminated with TOCP, which can produce a delayed neurodegenerative syndrome called OP-induced delayed neuropathy (OPIDN) in human beings and sensitive species. 4,5 Since then, similar symptoms have also occurred in other parts of the world. 6,7 OPIDN is characterized by distal axonal lesions, ataxia, and neuronal degeneration in the spinal cord andthe peripheral nervous systems. 6,8,9 Apart from neurotoxicity, it has been found that TOCP exposure can induce the reproductive toxicology. 1,10 Studies 11,12 have demonstrated that TOCP treatment for 5 or 63 days decreased the motility and density of cauda epididymal sperm and inhibited testicular enzymes activity in a dose-dependent manner and changed sperm morphology in male rats. Chen et al 1,13 found that TOCP suppressed the viability and proliferation of rat spermatogonial stem cells by inducing cell autophagy or inhibiting the neuropathy target esterase.Incubations with TOCP for 48 hours significantly decreased the viability and testosterone secretion of mouse Leydig TM3 cells via the