Exposure in utero to 2,2′,3,3′,4,6′-hexachlorobiphenyl (PCB 132) impairs sperm function and alters testicular apoptosis-related gene expression in rat offspring
Exposure in utero to 2,2′,3,3′,4,6′-hexachlorobiphenyl (PCB 132) impairs sperm function and alters testicular apoptosis-related gene expression in rat offspring
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DOI：
10.1016/j.taap.2007.01.027
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发表时间：
2007-05-15
影响因子：
3.8
通讯作者：
Guo, Yueliang Leon
中科院分区：
文献类型：
--
作者：
Hsu, Ping-Chi;Pan, Min-Hsiung;Guo, Yueliang Leon
多氯联苯（PCBs）的毒性取决于其分子结构。产前接触非二恶英类多氯联苯2，2 '，3，4'，5 '，6-六氯联苯（PCB 132）可能影响雄性后代生殖途径的机制相对未知。目的是确定是否附睾精子功能和附睾相关基因的表达诱导或抑制产前暴露PCB 132。妊娠大鼠在妊娠第15天接受1或10 mg/kg PCB 132单次给药。在出生后第84天处死雄性后代，并评估附睾精子计数、活力、速度、活性氧（ROS）产生、精子-卵母细胞穿透率（SOPR）、睾丸组织病理学、睾丸变性相关基因表达和caspase活化。出生前暴露于PCB 132 1或10毫克/公斤的单剂量降低尾部附睾重量，附睾精子计数和活动的附睾精子计数在成年后代。暴露于PCB 132的后代的精子产生的ROS水平显著高于对照组; ROS诱导和SOPR减少与剂量相关。在低剂量PCB 132组中，p53被显著诱导，caspase-3被抑制。高剂量组caspase-3和caspase-9的活化明显增强，Fas、Bax、bcl-2和p53基因的表达明显降低。基因表达和半胱天冬酶激活数据可以提供对暴露于低剂量或高剂量PCB 132影响大鼠雄性后代生殖的机制的深入了解。由于给予母鼠的PCB 132剂量在低剂量组中约为人体组织浓度的625倍，在高剂量组中约为人体组织浓度的6250倍，因此这些浓度与生物学或环境无关。需要使用与环境有关的剂量进行进一步研究，以确定危害。(c)2007年爱思唯尔公司All rights reserved.
Toxicity of the polychlorinated biphenyls (PCBs) depends on their molecular structure. Mechanisms by prenatal exposure to a non-dioxin-like PCB, 2,2',3,4',5',6-hexachlorobiphenyl (PCB 132) that may act on reproductive pathways in male offspring are relatively unknown. The purpose was to determine whether epididymal sperm function and expression of apoptosis-related genes were induced or inhibited by prenatal exposure to PCB 132. Pregnant rats were treated with a single dose of PCB 132 at I or 10 mg/kg on gestational day 15. Male offspring were killed and the epididymal sperm counts, motility, velocity, reactive oxygen species (ROS) generation, sperm-oocyte penetration rate (SOPR), testicular histopathology, apoptosis-related gene expression and caspase activation were assessed on postnatal day 84. Prenatal exposure to PCB 132 with a single dose of 1 or 10 mg/kg decreased cauda epididymal weight, epididymal sperm count and motile epididymal sperm count in adult offspring. The spermatozoa of PCB 132-exposed offspring produced significantly higher levels of ROS than the controls; ROS induction and SOPR reduction were dose-related. In the low-dose PCB 132 group, p53 was significantly induced and caspase-3 was inhibited. In the high-dose group, activation of caspase-3 and -9 was significantly increased, while the expressions of Fas, Bax, bcl-2, and p53 genes were significantly decreased. Gene expression and caspase activation data may provide insight into the mechanisms by which exposure to low-dose or high-dose PCB 132 affects reproduction in male offspring in rats. Because the doses of PCB 132 administered to the dams were approximately 625-fold in low-dose group and 6250-fold higher in high-dose group than the concentration in human tissue levels, the concentrations are not biologically or environmentally relevant. Further studies using environmentally relevant doses are needed for hazard identification. (c) 2007 Elsevier Inc. All rights reserved.