Chen Haiqiong, Xin Xiu, Liu Miaoqing, Ma Feifei, Yu Yige, Huang Jie, Dai Haipeng, Li Zhongrong, Ge Ren-Shan
Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Toxicol Appl Pharmacol. 2021 May 15;419:115514. doi: 10.1016/j.taap.2021.115514. Epub 2021 Mar 30.
Phthalates as plasticizers are widely used in many consumer products. Dipentyl phthalate (DPeP) is one of phthalates. However, there are currently few data on whether DPeP exposure affects rat Leydig cell development. In this study, we investigated the effects of in utero DPeP exposure on Leydig cell development in the testes of male newborn and adult rats. From gestational days 14 to 21, Sprague-Dawley pregnant rats were gavaged vehicle (corn oil, control) or DPeP (10, 50, 100, and 500 mg/kg body weight/day). Testosterone and the expression of Leydig cell genes and proteins in the testis at birth and at postnatal day 56 were examined. DPeP dose-dependently reduced serum testosterone levels of male offspring at birth and at postnatal day 56 at 100 and 500 mg/kg and lowered serum luteinizing hormone levels at adult males at ≥10 mg/kg when compared with the control. In addition, DPeP increased number of fetal Leydig cells by inducing their proliferation but down-regulated the expression of Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, and Insl3 in fetal Leydig cells per se. DPeP reduced number of adult Leydig cells by inducing cell apoptosis and down-regulated the expression of Lhcgr and Star in adult Leydig cells at postnatal day 56. DPeP lowered SIRT1 and BCL2 levels in the testis of adult rats. In conclusion, DPeP adversely affects both fetal and adult Leydig cell development after in utero exposure.
邻苯二甲酸酯作为增塑剂被广泛应用于许多消费品中。邻苯二甲酸二戊酯（DPeP）是邻苯二甲酸酯类之一。然而，目前关于DPeP暴露是否影响大鼠睾丸间质细胞发育的数据较少。在本研究中，我们调查了子宫内暴露于DPeP对雄性新生大鼠和成年大鼠睾丸间质细胞发育的影响。从妊娠第14天至21天，给Sprague-Dawley孕鼠灌胃给予溶剂（玉米油，对照组）或DPeP（10mg/kg、50mg/kg、100mg/kg和500mg/kg体重/天）。检测出生时和出生后第56天睾丸中睾酮以及睾丸间质细胞基因和蛋白的表达。与对照组相比，DPeP在100mg/kg和500mg/kg剂量时可剂量依赖性降低出生时和出生后第56天雄性后代的血清睾酮水平，在≥10mg/kg时可降低成年雄性大鼠的血清黄体生成素水平。此外，DPeP通过诱导胎儿睾丸间质细胞增殖增加其数量，但下调其自身中Lhcgr、Scarb1、Star、Cyp11a1、Hsd3b1、Cyp17a1、Hsd17b3和Insl3的表达。DPeP通过诱导细胞凋亡减少成年睾丸间质细胞数量，并下调出生后第56天成年睾丸间质细胞中Lhcgr和Star的表达。DPeP降低成年大鼠睾丸中SIRT1和BCL2水平。总之，子宫内暴露于DPeP会对胎儿和成年睾丸间质细胞发育产生不利影响。
