ICT2025 - lUTOX 17th International Congress of Toxicology

Date	Time	Local Time	Room	Forum	Session	Role	Topic
2025-10-17	09:45-10:00	2025-10-17,09:45-10:00	Room A - Guojin Hall	Symposium Program （Session）	Young Scientist Lecture 01：Advances in Feed Safety and Toxicology: From Detection and Toxicological Evaluation to Risk Management and Control	Speaker	Effects of phthalate exposure on the male reproductive system and antagonism of lycopene Objectives: Male infertility is an attracting growing concern owing to decline in sperm quality of men worldwide. Phthalates, in particular to di (2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP), affect male reproductive development and function, which mainly accounts for reduction in male fertility^[1]. Lycopene (LYC) is a natural antioxidant agent that has been recognized as a possible therapeutic option for treating male infertility^[2]. How DEHP causes spermatogenesis disturbance and whether LYC can prevent DEHP-induced male reproductive toxicity have remained unclear. Methods: In this study, the mice and testicular cell line (GC-1, TM3, TM4) were treated with LYC, DEHP and/or MEHP. Results: Using in vivo and vitro approaches, we demonstrated that DEHP induced growing developmental disorders, spermatogenic dysfunction, testosterone synthesis disorder, and blood-testis barrier (BTB) destruction. Mechanistically, DEHP induced Sertoli cell ferroptosis by activating transferrin receptor (TFRC)-mediated imbalance in iron homeostasis and lipid peroxidation. Of note, DEHP did not induce Leydig cell ferroptosis but synergizes Erastin-induced ferroptosis by inhibiting solute carri1er family 7 member 11 (SLC7A11) expression. Furthermore, LYC could reduce the accumulation of DEHP metabolites in mouse testicular tissue, thereby reducing the toxic effect of DEHP. LYC also prevented DEHP-induced male reproductive toxicity by regulating Connexin-43 (Cx43) and testosterone/androgen receptor pathway signaling pathway. Conclusions: Our study establishes a correlation between ferroptosis and phthalates cytotoxicity, providing a novel view point for mitigating the issue of male reproductive disease and “The Global Plastic Toxicity Debt”. This research also provides new evidence for the molecular mechanism of LYC antagonizing phthalate-induced male reproductive toxicity.

Objectives: Male infertility is an attracting growing concern owing to decline in sperm quality of men worldwide. Phthalates, in particular to di (2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP), affect male reproductive development and function, which mainly accounts for reduction in male fertility^[1]. Lycopene (LYC) is a natural antioxidant agent that has been recognized as a possible therapeutic option for treating male infertility^[2]. How DEHP causes spermatogenesis disturbance and whether LYC can prevent DEHP-induced male reproductive toxicity have remained unclear.

Methods: In this study, the mice and testicular cell line (GC-1, TM3, TM4) were treated with LYC, DEHP and/or MEHP.

Results: Using in vivo and vitro approaches, we demonstrated that DEHP induced growing developmental disorders, spermatogenic dysfunction, testosterone synthesis disorder, and blood-testis barrier (BTB) destruction. Mechanistically, DEHP induced Sertoli cell ferroptosis by activating transferrin receptor (TFRC)-mediated imbalance in iron homeostasis and lipid peroxidation. Of note, DEHP did not induce Leydig cell ferroptosis but synergizes Erastin-induced ferroptosis by inhibiting solute carri1er family 7 member 11 (SLC7A11) expression. Furthermore, LYC could reduce the accumulation of DEHP metabolites in mouse testicular tissue, thereby reducing the toxic effect of DEHP. LYC also prevented DEHP-induced male reproductive toxicity by regulating Connexin-43 (Cx43) and testosterone/androgen receptor pathway signaling pathway.

Conclusions: Our study establishes a correlation between ferroptosis and phthalates cytotoxicity, providing a novel view point for mitigating the issue of male reproductive disease and “The Global Plastic Toxicity Debt”. This research also provides new evidence for the molecular mechanism of LYC antagonizing phthalate-induced male reproductive toxicity.