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.
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 micrograms 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 F0 (no developmental exposure) generation at 0.01 microgram/kg/day in the diet. Furthermore, administration of TCDD on GD 15 (at 0.064 to 1 microgram/kg) both demasculinized and feminized morphology and behavior of Holtzman male rat offspring. Our objectives were to expand the observations of Mably et 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 microgram 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 micrograms/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.
Gray
L E
LE
Developmental Reproductive Biology Section, DTD, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Kelce
W R
WR
Monosson
E
E
Ostby
J S
JS
Birnbaum
L S
LS
D000375:Aging / Q000502:physiology; D000728:Androgens / Q000502:physiology*; D000818:Animals; D006224:Cricetinae; D004542:Ejaculation / Q000187:drug effects*; D004822:Epididymis / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000187:drug effects; D005837:Genitalia, Male / Q000033:anatomy & histology / Q000187:drug effects* / Q000254:growth & development*; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011467:Prostate / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000378:metabolism / Q000502:physiology*; D012669:Seminal Vesicles / Q000378:metabolism / Q000648:ultrastructure; D012726:Sexual Behavior, Animal / Q000187:drug effects; D012741:Sexual Maturation / Q000187:drug effects; D013076:Sperm Count / Q000187:drug effects*; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis / Q000097:blood
D000728:Androgens; D000072317:Polychlorinated Dibenzodioxins; D011944:Receptors, Androgen; D013739:Testosterone; D007986:Luteinizing Hormone