3-(4-メチルベンジリデン)樟脳の生殖毒性と抗アンドロゲン性

3-(4-Methylbenzylidene) camphor induced reproduction toxicity and antiandrogenicity in Japanese medaka (Oryzias latipes).

• Mengmeng Liang
• Saihong Yan
• Rui Chen
• Xiangsheng Hong
• Jinmiao Zha

抄録

3-(4-メチルベンジルリデン)樟脳(4-MBC)のメダカの繁殖と発育に及ぼす環境中濃度の毒性を評価するために、ペアメダカ成虫(F0)を5, 50, 500μg/Lの4-MBCに28日間曝露した。その結果、500μg/L 4-MBCでは繁殖力が有意に低下した（p＜0.05）。組織学的観察では、F0オスの精子形成は、50および500μg/L 4-MBCで有意に阻害され、血漿11-ケトステロンの全処置で得られた効果と同様であった(p<0.05)。さらに、F0メスの血漿ビテロジェニンおよびエストラジオールレベルは、5μg/L 4-MBCで有意に上昇した(p<0.05)。男性の脳と生殖腺で試験した視床下部-下垂体-性腺（HPG）軸関連遺伝子の転写物はすべての治療法で有意に増加し、肝臓ではerα、erβ、vtgで得られた効果と同様であり、肝臓ではarαで得られた効果とは対照的であった（p<0.05）。同数の胚を水道水と4-MBC溶液に曝露した。500μg/Lの4-MBC処理では、孵化までの時間の有意な増加、孵化率の低下、孵化後14日目の体長の減少が得られた（p<0.05）。孵化後14日目の累積死亡率はすべての処理で有意に増加した(p<0.05)。以上のことから、50μg/Lおよび500μg/Lの4-MBCに長期暴露すると生殖・発達毒性が生じることが明らかになり、日本産メダカの抗アンドロゲン性および4-MBCのメカニズムについて新たな知見を得ることができた。

To assess the toxic effects of 3-(4-Methylbenzylidene) camphor (4-MBC) at environmentally relevant concentrations on the reproduction and development of Japanese medaka (Oryzias latipes), adult paired medaka (F0) were exposed to 5, 50, and 500 μg/L 4-MBC for 28 d in the current study. The fecundity and fertility were significantly decreased at 500 μg/L 4-MBC (p < 0.05). Histological observations showed that spermatogenesis in F0 males was significantly inhibited at 50 and 500 μg/L 4-MBC, similar to the effects obtained with all treatments of plasma 11-ketotestosterone (p < 0.05). Moreover, the plasma vitellogenin and estradiol levels in F0 females were significantly increased at 5 μg/L 4-MBC (p < 0.05). All the transcripts of hypothalamic-pituitary-gonadal (HPG) axis-related genes tested in the brains and gonads of males were significantly increased at all treatments, similar to the effects obtained for erα, erβ and vtg in the livers and in contrast to those found for arα in the livers (p < 0.05). Equal numbers of embryos were exposed to tap water and 4-MBC solutions. Significantly increased times to hatching, decreased hatching rates and decreased body lengths at 14-day post-hatching (dph) were obtained at 500 μg/L 4-MBC treatment (p < 0.05). The cumulative death rates at 14 dph were significantly increased with all the treatments (p < 0.05). Therefore, our results showed that long-term exposure to 50 and 500 μg/L 4-MBC causes reproductive and developmental toxicity and thus provide new insight into antiandrogenicity and the mechanism of 4-MBC in Japanese medaka.

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