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产前暴露于黄曲霉毒素B1:雄性大鼠的发育、行为和生殖改变

Prenatal exposure to aflatoxin B1: developmental, behavioral, and reproductive alterations in male rats.

作者信息

Supriya Ch, Reddy P Sreenivasula

机构信息

Department of Biotechnology, Sri Venkateswara University, Tirupati, 517502, India.

出版信息

Naturwissenschaften. 2015 Jun;102(5-6):26. doi: 10.1007/s00114-015-1274-7. Epub 2015 Apr 25.

DOI:10.1007/s00114-015-1274-7
PMID:25911313
Abstract

Previous studies have shown that aflatoxin B1 (AfB1) inhibits androgen biosynthesis as a result of its ability to form a high-affinity complex with the steroidogenic acute regulatory protein. The results of the present study demonstrate the postnatal effects of in utero exposure to AfB1 in the rat. Pregnant Wistar rats were given 10, 20, or 50 μg AfB1/kg body weight daily from gestation day (GD) 12 to GD 19. At parturition, newborns were observed for clinical signs and survival. All animals were born alive and initially appeared to be active. Male pups from control and AfB1-exposed animals were weaned and maintained up to postnatal day (PD) 100. Litter size, birth weight, sex ratio, survival rate, and crown-rump length of the pups were significantly decreased in AfB1-exposed rats when compared to controls. Elapsed time (days) for testes to descend into the scrotal sac was significantly delayed in experimental pups when compared to control pups. Behavioral observations such as cliff avoidance, negative geotaxis, surface rightening activity, ascending wire mesh, open field behavior, and exploratory and locomotory activities were significantly impaired in experimental pups. Body weights and the indices of testis, cauda epididymis, prostate, seminal vesicles, and liver were significantly reduced on PD 100 in male rats exposed to AfB1 during embryonic development when compared with controls. Significant reduction in the testicular daily sperm production, epididymal sperm count, and number of viable, motile, and hypo-osmotic tail coiled sperm was observed in experimental rats. The levels of serum testosterone and activity levels of testicular hydroxysteroid dehydrogenases were significantly decreased in a dose-dependent manner with a significant increase in the serum follicle-stimulating hormone and luteinizing hormone in experimental rats. Deterioration in the testicular and cauda epididymal architecture was observed in experimental rats. The results of fertility studies revealed a significant decrease in the mating index in experimental rats with an increase in the pre- and post-implantation losses in rats mated with prenatal AfB1-exposed males, indicating poor male reproductive performance. These results indicate that in utero exposure to AfB1 severely compromised postnatal development of neonatal rats, and caused a delay in testes descent and reduction in steroidogenesis and spermatogenesis that were accomplished by suppressed reproduction at adulthood.

摘要

先前的研究表明,黄曲霉毒素B1(AfB1)能够与类固醇生成急性调节蛋白形成高亲和力复合物,从而抑制雄激素的生物合成。本研究结果证明了子宫内暴露于AfB1对大鼠出生后的影响。从妊娠第12天(GD 12)至妊娠第19天(GD 19),每天给怀孕的Wistar大鼠腹腔注射10、20或50μg/kg体重的AfB1。分娩时,观察新生大鼠的临床症状和存活率。所有动物均存活出生,最初看起来活动正常。将对照组和暴露于AfB1的动物的雄性幼崽断奶,并饲养至出生后第100天(PD 100)。与对照组相比,暴露于AfB1的大鼠幼崽的窝仔数、出生体重、性别比例、存活率和冠臀长度均显著降低。与对照幼崽相比,实验幼崽睾丸降入阴囊囊的时间(天数)显著延迟。实验幼崽的行为观察,如避崖、负趋地性、表面翻正活动、攀爬金属丝网、旷场行为以及探索和运动活动均受到显著损害。与对照组相比,在胚胎发育期间暴露于AfB1的雄性大鼠在PD 100时体重以及睾丸、附睾尾、前列腺、精囊和肝脏的指数均显著降低。实验大鼠的睾丸每日精子产量、附睾精子计数以及活的、有活力的和低渗尾卷曲精子的数量均显著减少。实验大鼠血清睾酮水平和睾丸羟类固醇脱氢酶活性水平呈剂量依赖性显著降低,血清促卵泡激素和促黄体生成素显著升高。实验大鼠的睾丸和附睾尾结构出现退化。生育力研究结果显示,实验大鼠的交配指数显著降低,与产前暴露于AfB1的雄性大鼠交配的大鼠着床前和着床后损失增加,表明雄性生殖性能较差。这些结果表明,子宫内暴露于AfB1会严重损害新生大鼠的出生后发育,并导致睾丸下降延迟以及类固醇生成和精子发生减少,而这是通过成年期生殖功能受抑制实现的。

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