EXPOSURE TO TCDD DURING DEVELOPMENT PERMANENTLY ALTERS REPRODUCTIVE FUNCTION IN MALE LONG-EVANS RATS AND HAMSTERS - REDUCED EJACULATED AND EPIDIDYMAL SPERM NUMBERS AND SEX ACCESSORY-GLAND WEIGHTS IN OFFSPRING WITH NORMAL ANDROGENIC STATUS
EXPOSURE TO TCDD DURING DEVELOPMENT PERMANENTLY ALTERS REPRODUCTIVE FUNCTION IN MALE LONG-EVANS RATS AND HAMSTERS - REDUCED EJACULATED AND EPIDIDYMAL SPERM NUMBERS AND SEX ACCESSORY-GLAND WEIGHTS IN OFFSPRING WITH NORMAL ANDROGENIC STATUS
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DOI：
10.1006/taap.1995.1052
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发表时间：
1995-03-01
影响因子：
3.8
通讯作者：
BIRNBAUM, LS
中科院分区：
文献类型：
--
作者：
GRAY, LE;KELCE, WR;BIRNBAUM, LS
产前给予相对低剂量的TCDD会改变后代的生殖发育和生育力。从妊娠第6天（GD）至GD 15天，Wistar大鼠后代暴露于0.5 μ g TCDD/kg/天，生育能力降低。在一项三代生殖研究中，饲料中0.01 μ g/kg/天的四氯二苯并对二恶英降低了F1和F2代Sprague-Dawley大鼠的生育力，但对FD（无发育暴露）代大鼠没有影响。此外，在GD 15给予TCDD（0.064至1 μ g/kg），Holtzman雄性大鼠后代的形态和行为均出现去雄性化和雌性化。我们的目标是扩展Mably等人（1992，Toxicol.应用药理学114，97-107，108-117，118-126）对妊娠期给予另一种大鼠品系和另一种物种仓鼠单剂量TCDD的影响。在第一项研究中，在GD 8（主要器官形成期间）或GD 15（Mably等人使用的妊娠日），对Long Evans（LE）hooded大鼠灌胃1 μ g TCDD/kg。在第二项研究中，怀孕的叙利亚仓鼠（一种对四氯二苯并对二恶英致死效应相对不敏感的物种）在GD 11（相当于大鼠GD 15）接受剂量为2 μ g/kg的四氯二苯并对二恶英给药。当LE大鼠在GD 15给药或仓鼠在GD 11给药时，青春期（包皮分离）延迟约3天，射出的精子计数减少至少58%，附睾精子储存减少38%。睾丸精子的产生受到的影响较小。在GD 15处理的LE大鼠后代中，性附属腺的大小也减小，尽管血清睾酮（T）、睾丸体外T生成和雄激素受体（AR）水平未降低。一些生殖措施，如肛门生殖器的距离和男性性行为，改变了TCDD治疗大鼠，但不仓鼠后代。由于围产期TCDD暴露后，性附腺和附睾中的T和AR水平似乎正常，因此这些组织的变化不太可能是由于雄性后代雄激素状态的改变引起的。(C)出版社：Academic Press
Prenatal administration of relatively low doses of TCDD alters reproductive development and fertility of the progeny. Fertility was reduced in the progeny of Wistar rats exposed to 0.5 mu g TCDD/kg/day from Gestational Day (GD) 6 to GD 15. In a three-generation reproduction study, TCDD reduced fertility of Sprague-Dawley rats in the F1 and F2 but not the FD (no developmental exposure) generation at 0.01 mu g/kg/day in the diet. Furthermore, administration of TCDD on GD 15 (at 0.064 to I mu g/kg) both demasculinized and feminized morphology and behavior of Holtzman male rat offspring. Our objectives were to expand the observations of Mably ef al. (1992, Toxicol. Appl. Pharmacol. 114, 97-107, 108-117, 118-126) on the effects of gestational administration of a single dose of TCDD to another strain of rat and another species, the hamster. In the first study, Long Evans (LE) hooded rats were dosed by gavage with 1 mu g TCDD/kg on GD 8 (during the period of major organogenesis) or GD 15 (the gestational day used by Mably et al.). In the second study, pregnant Syrian hamsters, a species relatively insensitive to the lethal effects of TCDD, were dosed on GD 11, equivalent to GD 15 in the rat, with TCDD at 2 mu g/kg. When LE rats were dosed on GD 15, or when hamsters were dosed on GD 11, puberty (preputial separation) was delayed by about 3 days, ejaculated sperm counts were reduced by at least 58%, and epididymal sperm storage was reduced by 38%. Testicular sperm production was less affected. The sex accessory glands were also reduced in size in LE rat offspring treated on GD 15 despite the fact that serum testosterone (T), T production by the testis in vitro, and androgen receptor (AR) levels were not reduced. Some reproductive measures, such as anogenital distance and male sex behavior, were altered by TCDD treatment in rat but not hamster offspring. Since T and AR levels appeared normal in the sex accessory glands and the epididymis following perinatal TCDD exposure, the alterations in these tissues are not likely to have resulted from an alteration of the androgenic status of the male offspring. (C) 1995 Academic Press, Inc.