Prenatal exposure to vinclozolin disrupts selective aspects of the gonadotrophin-releasing hormone neuronal system of the rabbit.
Prenatal exposure to vinclozolin disrupts selective aspects of the gonadotrophin-releasing hormone neuronal system of the rabbit.
复制标题
产前接触乙烯菌核利会破坏兔子促性腺激素释放激素神经系统的选择性方面。
DOI：
10.1111/j.1365-2826.2010.01973.x
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发表时间：
2010
影响因子：
3.2
通讯作者：
Tobet,SA
中科院分区：
文献类型：
--
作者：
Wadas,BC;Hartshorn,CA;Aurand,ER;Palmer,JS;Roselli,CE;Noel,ML;Gore,AC;Veeramachaneni,DNR;Tobet,SA
孕期暴露于农用杀菌剂长春新灵可损害雄兔的生殖功能，早先发现在出生后一周( 6)会减少终板血管器区和头端视前区促性腺激素释放激素免疫反应神经元的数量。在本研究中，为了进一步研究胎兔暴露于长春花灵对促性腺激素释放激素神经元的破坏作用，在妊娠的最后2周内，给妊娠兔口服长春花灵、氟他胺或胡萝卜糊载体。后代在出生时被安乐死(男性和女性)，PNW 6(女性)，PNW 26(成年男性)或PNW 30(成年女性)。出生时和成年时，对大脑进行切片和处理，以检测GnRH的免疫反应。经长春花碱处理的兔生后和成年后，GnRH免疫反应阳性神经元的数目明显减少。相反，正中隆起区终末的GnRH免疫反应增强。用放射免疫法分析pNW- -6雌性兔脑内的GnRH肽含量，发现注射长春花碱的兔下丘脑下丘脑内侧基底区GnRH肽含量增加了一倍。这一发现得到了免疫荧光分析的补充，免疫荧光分析显示，在PNW 30，长春花碱中隆起的促性腺激素释放激素免疫反应性是使用赋形剂的女性的2.8倍。然而，在评估的生殖指标中，治疗组之间没有差异：射精潜伏期、受孕率或产仔数。这些结果表明，亚急性、产前的长春新碱治疗足以在GnRH神经网络中产生持久的改变，这构成了生殖轴的重要输入。最后，长春花碱对GnRH神经元网络的作用不能与氟他胺相提并论，这表明长春花碱不是通过抗雄激素机制发挥作用的。
Developmental exposure to the agricultural fungicide vinclozolin can impair reproductive function in male rabbits and was previously found to decrease the number of immunoreactive‐gonadotrophin‐releasing hormone (GnRH) neurones in the region of the organum vasculosum of the lamina terminalis and rostral preoptic area by postnatal week (PNW) 6. In the present study, in an aim to further examine the disruption of GnRH neurones by foetal vinclozolin exposure, pregnant rabbits were dosed orally with vinclozolin, flutamide or carrot paste vehicle for the last 2 weeks of gestation. Offspring were euthanised at birth (males and females), PNW 6 (females), PNW 26 (adult males) or PNW 30 (adult females) of age. At birth and in adults, brains were sectioned and processed for immunoreactive GnRH. The numbers of immunoreactive GnRH neuronal perikarya were significantly decreased in vinclozolin‐treated rabbits at birth and in adult littermates. By contrast, there was an increase in GnRH immunoreactivity in the terminals in the region of the median eminence. Analysis of PNW 6 female brains by radioimmunoassay revealed a two‐fold increase in GnRH peptide content in the mediobasal hypothalamus in vinclozolin‐treated rabbits. This finding was complemented by immunofluorescence analyses, which revealed a 2.8‐fold increase in GnRH immunoreactivity in the median eminence of vinclozolin compared to vehicle‐treated females at PNW 30. However, there was no difference between treatment groups in the measures of reproduction that were evaluated: ejaculation latency, conception rates or litter size. These results indicate that sub‐acute, prenatal vinclozolin treatment is sufficient to create perdurable alterations in the GnRH neuronal network that forms an important input into the reproductive axis. Finally, the effect of vinclozolin on the GnRH neuronal network was not comparable to that of flutamide, suggesting that vinclozolin was not acting through anti‐androgenic mechanisms.