Prenatal exposure to di-n-butyl phthalate disrupts the development of adult Leydig cells in male rats during puberty
Prenatal exposure to di-n-butyl phthalate disrupts the development of adult Leydig cells in male rats during puberty
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产前接触邻苯二甲酸二正丁酯会扰乱青春期雄性大鼠成年间质细胞的发育
DOI：
10.1016/j.tox.2017.05.004
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发表时间：
2017-07-01
期刊：
影响因子：
4.5
通讯作者：
Ge, Ren-Shan
中科院分区：
文献类型：
--
作者：
Chen, Xiaomin;Li, Linxi;Ge, Ren-Shan
胎儿暴露于邻苯二甲酸二丁酯（DBP）会导致成人疾病，如睾丸激素分泌减少和不育。然而，其机制仍然未知。本研究的目的是确定DBP如何影响新生儿期胎儿间质细胞的退化，以及该事件如何导致青春期成人间质细胞发育延迟。将妊娠Sprague道利母兽随机分为3组，从妊娠第12天（G12）至G21，分别灌胃0（玉米油，溶剂对照）、100或500 mg/kg DBP。在出生后第4天（P4）、P7、P14、P21、P28和P56采集雄性幼仔的血液和睾丸。血清睾酮浓度进行了评估和睾丸间质细胞或促性腺激素细胞特异性基因的mRNA水平进行了测量。出生前暴露于DBP导致胎儿Leydig细胞聚集，与对照组相比，这些细胞逐渐消失。这种作用与睾丸睾酮分泌减少和间质细胞生物标志物（包括Scarb 1、星星、Cypllal、Hsd 3b 1、Hsdllbl和Hsdl 7 b3）以及促性腺激素生物标志物（包括Lhb和Gnrhr）的mRNA水平下调有关。总之，我们证明了DBP增加胎儿间质细胞的聚集延迟了胎儿间质细胞的退化，从而导致成体间质细胞的发育中断。
Fetal exposure to di-n-butyl phthalate (DBP) causes the adult disease such as lower testosterone production and infertility. However, the mechanism is still unknown. The objective of the present study is to determine how DBP affects the involution of fetal Leydig cells during the neonatal period and how this event causes the delayed development of the adult Leydig cells during puberty. The pregnant Sprague Dawley dams were randomly divided into 3 groups and were gavaged with 0 (corn oil, the vehicle control), 100 or 500 mg/kg DBP from gestational day 12 (G12) to G21. The blood and testes were collected from male pups on postnatal day 4 (P4), P7, P14, P21, P28, and P56. Serum testosterone concentrations were assessed and the mRNA levels of Leydig cell- or gonadotroph cell-specific genes were measured. Prenatal exposure to DBP caused the aggregation of fetal Leydig cells, which slowly disappeared when compared to the control. This effect was associated with the reduction of testicular testosterone secretion and down-regulation of the mRNA levels of Leydig cell biomarkers including Scarb1, Star, Cypllal, Hsd3b1, Hsdllbl, and Hsdl7b3 as well as the gonadotroph biomarkers including Lhb and Gnrhr. In conclusion, we demonstrated that the increased aggregation of fetal Leydig cells by DBP delayed fetal Leydig cell involution, thus leading to the disrupted development of the adult Leydig cells.