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首页> 外文期刊>Reproductive toxicology >Actions of the endocrine disruptor methoxychlor and its estrogenic metabolite on in vitro embryonic rat seminiferous cord formation and perinatal testis growth.
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Actions of the endocrine disruptor methoxychlor and its estrogenic metabolite on in vitro embryonic rat seminiferous cord formation and perinatal testis growth.

机译：内分泌干​​扰物甲氧氯及其雌激素代谢物对体外胚胎大鼠生精带形成和围产期睾丸生长的作用。

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摘要

The current study examines the actions of methoxychlor and its estrogenic metabolite, 2, 2-bis-(p-hydroxyphenyl)-1, 1, 1-trichloroethane (HPTE), on seminiferous cord formation and growth of the developing rat testis. The developing testis in the embryonic and early postnatal period is likely more sensitive to hormonally active agents than at later stages of development. Embryonic day 13 (E13) testis organ cultures were treated with either 0.2, 2, or 20 microM methoxychlor or 1, 3, 6, 15, 30, or 60 microM HPTE to examine effects on cord formation. No concentration of methoxychlor completely inhibited cord formation. However, cord formation was abnormal with the presence of a reduced number of cords and appearance of "swollen" cords at the 2 and 20 microM concentrations of methoxychlor. The swollen cords were due to an increase in the number of cells in a cord cross section and reduction of interstitial cell numbers between cords. Treatment of embryonic day 13 (E13) testes with HPTE caused abnormal cord formation at the 3 microM and 6 microM concentrations, and completely inhibited cord formation at the 15, 30, and 60 microM concentrations. In addition to the estrogenic metabolite HTPE, methoxychlor can also be metabolized into anti-androgenic compounds. Therefore, to determine the spectrum of potential actions of methoxychlor on testis development, different concentrations of estradiol, testosterone, and an anti-androgen (flutamide) were utilized to determine their effects on E13 testis organ culture morphology. Estradiol (1 microM) and flutamide (0.1microM) both inhibited seminiferous cord formation in E13 testis organ cultures. Therefore, methoxychlor may be acting through the androgen and/or estrogen receptors to elicit its actions on seminiferous cord formation. Reverse transcription polymerase chain reaction (PCR) (RT-PCR) confirmed the presence of estrogen receptor alpha (ERalpha) mRNA from embryonic day 14 (E14) through postnatal day 5 (P5) while estrogen receptor beta (ERbeta) mRNA did not appear until approximately E16 of testis development. Androgen receptor (AR) expression was present from E14 through P5 of testis development, but at apparently reduced levels at E14 and E16. Immunohistochemical analysis localized ERalpha to the cells of the seminiferous cords at E14 though P5 while ERbeta was present in cells of the interstitium at E16 and P0. Androgen receptor was localized to germ and interstitial cells. The effects of methoxychlor, HPTE, estradiol, and testosterone on cell growth of perinatal testes was determined with a thymidine incorporation assay in postnatal day zero (P0) testis cell cultures. Methoxychlor (0.002, 0.02, and 0.2 microM) and HPTE (2 and 20 microM) stimulated thymidine incorporation in P0 testis cell cultures in a similar manner to estradiol (0.01, 0.1, and 1 microM). In addition, testosterone (0.1 microM) also stimulated thymidine incorporation in P0 testis cultures. Observations suggest that methoxychlor and its metabolite HPTE can alter normal embryonic testis development and growth. The actions of methoxychlor and HPTE are likely mediated in part through the steroid receptors confirmed to be present in the developing testis.
机译：目前的研究检查了甲氧基氯及其雌激素代谢物2，2，2-双-（对羟基苯基）-1，1，1-三氯乙烷（HPTE）对生鼠睾丸生精索形成和生长的作用。与发育后期相比，胚胎期和出生后早期发育中的睾丸对激素活性剂更敏感。胚胎第13天（E13）的睾丸器官培养物用0.2、2或20 microM甲氧基氯或1，3、6、15、30或60 microM HPTE处理，以检查对脐带形成的影响。没有浓度的甲氧氯完全抑制脐带形成。但是，在2和20 microM甲氧基氯浓度下，存在数量减少的帘线并出现“肿胀”的帘线，帘线形成是异常的。脐带肿是由于脐带横截面中细胞数量的增加和脐带间质细胞数量的减少所致。用HPTE处理胚胎第13天（E13）睾丸会在3 microM和6 microM浓度下引起异常的脐带形成，并在15、30和60 microM浓度下完全抑制脐带形成。除雌激素代谢物HTPE外，甲氧基氯还可以代谢为抗雄激素化合物。因此，为了确定甲氧基氯对睾丸发育的潜在作用谱，利用不同浓度的雌二醇，睾丸激素和抗雄激素（氟他胺）来确定它们对E13睾丸器官培养形态的影响。雌二醇（1 microM）和氟他酰胺（0.1microM）均抑制E13睾丸器官培养物中的生精索形成。因此，甲氧氯可通过雄激素和/或雌激素受体起作用以引起其对生精索形成的作用。逆转录聚合酶链反应（PCR）（RT-PCR）证实从胚胎第14天（E14）到出生后第5天（P5）都存在雌激素受体α（ERalpha）mRNA，而直到出现雌激素受体β（ERbeta）mRNA为止大约是E16的睾丸发育。从E14到P5睾丸发育出现了雄激素受体（AR）表达，但在E14和E16的表达明显降低。免疫组织化学分析将ERalpha通过P5定位于E14的生精索细胞，而ERbeta存在于E16和P0的间质细胞中。雄激素受体定位于生殖细胞和间质细胞。在出生后第零天（P0）睾丸细胞培养物中，通过胸腺嘧啶核苷掺入试验确定甲氧氯，HPTE，雌二醇和睾丸激素对围产期睾丸细胞生长的影响。甲氧氯（0.002、0.02和0.2 microM）和HPTE（2和20 microM）以与雌二醇（0.01、0.1和1 microM）相似的方式刺激胸腺嘧啶核苷掺入P0睾丸细胞培养物中。此外，睾丸激素（0.1 microM）也刺激胸腺嘧啶核苷在P0睾丸培养物中的掺入。观察结果表明，甲氧氯及其代谢产物HPTE可以改变正常胚胎睾丸的发育和生长。甲氧基氯和HPTE的作用可能部分通过被证实存在于发育中的睾丸中的类固醇受体介导。

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