DEHP impairs zebrafish reproduction by affecting critical factors in oogenesis.
DEHP impairs zebrafish reproduction by affecting critical factors in oogenesis.
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DOI：
10.1371/journal.pone.0010201
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发表时间：
2010-04-15
期刊：
影响因子：
3.7
通讯作者：
Maradonna F
中科院分区：
文献类型：
--
作者：
Carnevali O;Tosti L;Speciale C;Peng C;Zhu Y;Maradonna F
邻苯二甲酸酯在环境中的分布越来越受到公众的关注，因为它们可以导致肝癌，结构异常和减少男性生殖系统的精子数量。然而，关于邻苯二甲酸二（2-乙基己基）酯（DEHP）对女性生殖系统影响的实际数据很少。本研究的目的是评估DEHP对斑马鱼卵子发生和胚胎生产的影响。雌性斑马鱼暴露于环境相关剂量的DEHP，观察到排卵和胚胎生产显著减少。通过真实的时间PCR测定DEHP对卵母细胞成熟和排卵的几种关键调节因子的影响，包括骨形态发生蛋白15（BMP 15）、促黄体生成激素受体（LHR）、膜孕酮受体（mPR）和环氧合酶（考克斯）-2（ptgs 2）。通过Western分析进一步确定BMP 15和mPR蛋白的表达以加强分子发现。此外，通过ELISA程序测定血浆卵黄蛋白原（vtg）滴度，以确定DEHP的雌激素效应及其对卵母细胞生长的影响。观察到接触DEHP的鱼类生殖力显著降低。生殖能力的降低与卵巢BMP 15水平的增加有关。这种升高反过来又伴随着LHR和mPRβ水平的显著降低。最后，PTGS 2表达，排卵的最终触发，也被DEHP降低。通过体外成熟试验，进一步证实了DEHP对胚泡破裂的抑制作用。总之，DEHP影响涉及卵母细胞生长（vtg）、成熟（BMP 15、LHR、mPR）和排卵（ptgs 2）的信号，严重损害卵巢功能，对胚胎生产造成严重后果。由于斑马鱼和人类之间存在显著的遗传相似性，因此在卵母细胞水平观察到的有害影响可能与人类的进一步分子研究有关。
Public concerns on phthalates distributions in the environment have been increasing since they can cause liver cancer, structural abnormalities and reduce sperm counts in male reproductive system. However, few data are actually available on the effects of Di-(2-ethylhexyl)-phthalate (DEHP) in female reproductive system. The aim of this study was to assess the impacts of DEHP on zebrafish oogenesis and embryo production. Female Danio rerio were exposed to environmentally relevant doses of DEHP and a significant decrease in ovulation and embryo production was observed. The effects of DEHP on several key regulators of oocyte maturation and ovulation including bone morphogenetic protein-15 (BMP15), luteinizing hormone receptor (LHR), membrane progesterone receptors (mPRs) and cyclooxygenase (COX)-2 (ptgs2) were determined by real time PCR. The expressions of BMP15 and mPR proteins were further determined by Western analyses to strengthen molecular findings. Moreover, plasma vitellogenin (vtg) titers were assayed by an ELISA procedure to determine the estrogenic effects of DEHP and its effects on oocyte growth. A significant reduction of fecundity in fish exposed to DEHP was observed. The reduced reproductive capacity was associated with an increase in ovarian BMP15 levels. This rise, in turn, was concomitant with a significant reduction in LHR and mPRβ levels. Finally, ptgs2 expression, the final trigger of ovulation, was also decreased by DEHP. By an in vitro maturation assay, the inhibitory effect of DEHP on germinal vesicle breakdown was further confirmed. In conclusion, DEHP affecting signals involved in oocyte growth (vtg), maturation (BMP15, LHR, mPRs,) and ovulation (ptgs2), deeply impairs ovarian functions with serious consequences on embryo production. Since there is a significant genetic similarity between D.rerio and humans, the harmful effects observed at oocyte level may be relevant for further molecular studies on humans.
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