大鼠孕期暴露于己烯雌酚会抑制经腹睾丸下降，该过程涉及胰岛素样肽3/促性腺激素释放激素受体8系统和同源盒A10。

Prenatal exposure to diaethylstilbestrol in the rat inhibits transabdominal testicular descent with involvement of the INSL3/LGR8 system and HOXA10.

作者信息

Zhang Lin, Zheng Xin-min, Hubert Jacques, Zheng Hang, Yang Zhi-wei, Li Shi-wen

机构信息

Department of Urology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, China.

出版信息

Chin Med J (Engl). 2009 Apr 20;122(8):967-71.

PMID:19493424

Abstract

BACKGROUND

Prenatal exposure to diaethylstilbestrol (DES) has been found to lead to intra-abdominal cryptorchidism, but the mechanism is still not completely clear. This study investigated the roles of the INSL3/LGR8 system and HOXA10 in DES-induced intra-abdominal cryptorchidism (DIIAC). The effect of DES on steroidogenic factor-1 (SF-1), that has been reported to control transcription of insulin-like factor 3 (INSL3), was also investigated.

METHODS

Fifty pregnant female SD rats at embryonic day 13.5 (E13.5) were randomly assigned to five groups that received a subcutaneous injections of dimethyl sulfoxide (control), 2.5 mg/kg, 5 mg/kg, 10 mg/kg, or 20 mg/kg of DES. Male offspring were sacrificed at E19.5, and fetal mortality and the degree of transabdominal testicular ascent (DTA) were determined under a stereomicroscope. The mRNA expression of INSL3 and SF-1 in the testis and leucine rich repeat-containing G protein-coupled receptors 8 (LGR8) and homeobox-A10 (HOXA10) in the gubernaculum were determined by RT-PCR. The expression of INSL3 protein was determined by Western blotting.

RESULTS

Higher fetal mortality and DTA were induced by DES in a dose-dependent manner (P < 0.01). Compared with the control group, the expression of INSL3 and SF-1 mRNA were down-regulated in a dose-dependent manner (P < 0.01), as was INSL3 protein; HOXA10 in the 2.5 mg/kg group and LGR8 mRNA in the 2.5 mg/kg and 5 mg/kg groups were not significantly different (P > 0.05); HOXA10 mRNA in groups C, D, and E decreased significantly and LGR8 mRNA levels in groups D and E increased significantly (P < 0.05, P < 0.01, respectively).

CONCLUSIONS

DES can inhibit transabdominal testicular descent in a dose-dependent manner via down-regulating the expression of INSL3, which is induced by down-regulating the expression of SF-1. HOXA10 may not be involved in DES induced intra-abdominal cryptorchidism at 2.5 mg/kg, but is involved at 5, 10 and 20 mg/kg. LGR8 may not be responsible for DES-induced transabdominal testicular maldescent.

摘要

背景

已发现产前暴露于己烯雌酚（DES）会导致腹内隐睾，但机制仍不完全清楚。本研究调查了胰岛素样肽3（INSL3）/富含亮氨酸重复序列的G蛋白偶联受体8（LGR8）系统和同源框A10（HOXA10）在DES诱导的腹内隐睾（DIIAC）中的作用。还研究了DES对类固醇生成因子-1（SF-1）的影响，据报道SF-1可控制胰岛素样因子3（INSL3）的转录。

方法

将50只孕13.5天（E13.5）的雌性SD大鼠随机分为五组，分别皮下注射二甲亚砜（对照组）、2.5mg/kg、5mg/kg、10mg/kg或20mg/kg的DES。在E19.5处死雄性后代，在体视显微镜下测定胎儿死亡率和经腹睾丸上升程度（DTA）。通过逆转录聚合酶链反应（RT-PCR）测定睾丸中INSL3和SF-1的mRNA表达以及睾丸引带中富含亮氨酸重复序列的G蛋白偶联受体8（LGR8）和同源框A10（HOXA10）的mRNA表达。通过蛋白质免疫印迹法测定INSL3蛋白的表达。

结果

DES以剂量依赖性方式诱导更高的胎儿死亡率和DTA（P<0.01）。与对照组相比，INSL3和SF-1的mRNA表达呈剂量依赖性下调（P<0.01），INSL3蛋白也是如此；2.5mg/kg组的HOXA10以及2.5mg/kg和5mg/kg组的LGR8 mRNA无显著差异（P>0.05）；C、D和E组的HOXA10 mRNA显著降低，D和E组的LGR8 mRNA水平显著升高（分别为P<0.05，P<0.01）。