Tri-ortho-cresyl phosphate (TOCP) has been used commercially as a plasticizer and a flame retardant, which has been reported to cause multiple toxicities in humans and other animals. However, the effect of TOCP on female reproductive system is still unclear. The aim of this investigation was to evaluate the reproductive toxicity of TOCP in female avian and investigate its molecular mechanism. In the current study, 50 adult hens were given a single oral dose of TOCP (750 mg/kg). Egg laid by the hens were harvested and counted. Egg quality is assessed by determining the shell strength and thickness. Samples of ovary, shell gland, and serum were collected on day 0, 2, 7, and 21 after the administration. The morphological and pathological changes in tissues were examined. Cell death, follicular development, and steroidogenesis were determined to assess the toxicity of TOCP on laying hens. The results showed that egg production, egg weight, and eggshell strength significantly decreased after TOCP exposure. The calcium levels in serum and eggshell decreased and the expression levels of the eggshell formation-related genes calbindin-D28k (CaBP-D28k) and carbonic anhydrase 2 (CA2) were downregulated. The inhibitory effects of TOCP on follicular development and steroidogenesis were observed with changes in the levels of the related proteins such as forkhead box O1 (FoxO1) and mothers against decapentaplegic homolog 2/3 (Smad2/3). Cell death was identified, which might lead to follicular development disorder. Taken together, TOCP reduced the quantity and quality of the eggs laid by the hens through disrupting follicular development, steroidogenesis, and shell gland function.

三邻磷酸甲酚酯 (TOCP) 已在商业上用作增塑剂和阻燃剂，据报道，它会对人类和其他动物造成多种毒性。然而，TOCP对女性生殖系统的影响尚不清楚。本研究旨在评价TOCP对雌性禽类的生殖毒性及其分子机制。在目前的研究中，给 50 只成年母鸡单次口服 TOCP（750 毫克/公斤）。母鸡下的蛋被收获并计数。通过确定蛋壳强度和厚度来评估鸡蛋质量。在给药后第0、2、7和21天收集卵巢、壳腺和血清样品。检查组织的形态学和病理学变化。细胞死亡、卵泡发育、和类固醇生成被确定来评估 TOCP 对蛋鸡的毒性。结果表明，TOCP暴露后产蛋量、蛋重和蛋壳强度均显着降低。血清和蛋壳中的钙水平降低，蛋壳形成相关基因钙结合蛋白-D28k（CaBP-D28k）和碳酸酐酶2（CA2）的表达水平下调。观察到 TOCP 对卵泡发育和类固醇生成的抑制作用随相关蛋白水平的变化，如 forkhead box O1 (FoxO1) 和母亲对 decapentaplegic 同源物 2/3 (Smad2/3) 的水平变化。确定了细胞死亡，这可能导致卵泡发育障碍。总之，TOCP 通过破坏卵泡发育、类固醇生成、