Toxicological Sciences, Vol 51, 259-264, Copyright © 1999 by Society of Toxicology
CJ Wolf, JS Ostby and LE Gray Jr
Low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), administered as a
single dose to the dam during gestation, alter development of the fetal
rodent reproductive system. In male rat and hamster offspring, dosing with
TCDD during gestation reduces epididymal and ejaculated sperm counts and
delays puberty. In female rats, in utero TCDD-exposure results in reduced
ovarian weight and fecundity, and induces cleft phallus and a persistent
thread of tissue across the vaginal orifice. Here, we demonstrate that
2-microgram TCDD/kg, administered as a single oral dose prior to sexual
differentiation, alters reproductive function in female hamster offspring,
a species relatively resistant to the lethal effects of TCDD. In the
current study, pregnant hamsters (P0 generation) were dosed orally with
vehicle (corn oil) or 2 micrograms TCDD/kg on gestational day (GD) 11.5. P0
maternal viability, body weight, fertility, and F1 litter size did not
differ between control and treated groups. In the F1 generation, body
weights were permanently reduced by about 30%, vaginal opening was delayed
(p < 0.0001), and vaginal estrous cycles were altered by TCDD treatment.
In contrast, most treated female offspring displayed regular 4-day
behavioral estrous cycles, indicating that in utero TCDD treatment did not
markedly disrupt hypothalamic-pituitary-gonadal hormonal cyclicity.
Although both control and TCDD-treated F1 females mated successfully with a
control male (estrous cyclicity was abolished by mating), 20% of the F1
treated females did not become not pregnant (no implants). In addition, 38%
of pregnant F1 females from the TCDD group died near- term, and the numbers
of implants in pregnant animals (treated 5.1 versus 11.3) and pups born
live (2.7 treated vs. 8.7 control) were reduced by TCDD-treatment. In the
F2, survival through weaning was drastically reduced (15% treated vs. 78%
for control) by TCDD treatment of P0 dams. F1 female hamster offspring
exposed in utero to TCDD displayed external urogenital malformations, with
most females having complete clefting of the phallus, an effect previously
reported in the rat. Unlike rats exposed to TCDD (0.2-1.0 microgram/kg) on
GD 15 or GD 8, hamster offspring did not display vaginal threads. These
results demonstrate that in utero administration of TCDD adversely affects
growth, reproductive function, and anatomy in female hamster offspring
given a dosage level nearly four orders of magnitude below the dosage level
toxic to the adult animal. Adverse effects of TCDD persisted through two
generations (F1 and F2), even though the F1 was only indirectly exposed
during gestation and lactation.
ARTICLES
Gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) severely alters reproductive function of female hamster offspring
Endocrinology Branch, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. K. Hotchkiss, C. V. Rider, C. R. Blystone, V. S. Wilson, P. C. Hartig, G. T. Ankley, P. M. Foster, C. L. Gray, and L. E. Gray Fifteen Years after "Wingspread"--Environmental Endocrine Disrupters and Human and Wildlife Health: Where We are Today and Where We Need to Go Toxicol. Sci., October 1, 2008; 105(2): 235 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Steinberg, D. M. Walker, T. E. Juenger, M. J. Woller, and A. C. Gore Effects of Perinatal Polychlorinated Biphenyls on Adult Female Rat Reproduction: Development, Reproductive Physiology, and Second Generational Effects Biol Reprod, June 1, 2008; 78(6): 1091 - 1101. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Nestler, M. Risch, B. Fischer, and P. Pocar Regulation of aryl hydrocarbon receptor activity in porcine cumulus-oocyte complexes in physiological and toxicological conditions: the role of follicular fluid Reproduction, May 1, 2007; 133(5): 887 - 897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Shi, K. E. Valdez, A. Y. Ting, A. Franczak, S. L. Gum, and B. K. Petroff Ovarian Endocrine Disruption Underlies Premature Reproductive Senescence Following Environmentally Relevant Chronic Exposure to the Aryl Hydrocarbon Receptor Agonist 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Biol Reprod, February 1, 2007; 76(2): 198 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Mueller, J.-L. Vigne, M. Streich, M. K. Tee, L. Raio, E. Dreher, N. A. Bersinger, and R. N. Taylor 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Increases Glycodelin Gene and Protein Expression in Human Endometrium J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4809 - 4815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Emond, L. S. Birnbaum, and M. J. DeVito Physiologically Based Pharmacokinetic Model for Developmental Exposures to TCDD in the Rat Toxicol. Sci., July 1, 2004; 80(1): 115 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Hamm, C.-Y. Chen, and L. S. Birnbaum A Mixture of Dioxins, Furans, and Non-ortho PCBs Based upon Consensus Toxic Equivalency Factors Produces Dioxin-Like Reproductive Effects Toxicol. Sci., July 1, 2003; 74(1): 182 - 191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Benedict, K. P. Miller, T.-M. Lin, C. Greenfeld, J. K. Babus, R. E. Peterson, and J. A. Flaws Aryl Hydrocarbon Receptor Regulates Growth, But Not Atresia, of Mouse Preantral and Antral Follicles Biol Reprod, May 1, 2003; 68(5): 1511 - 1517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Fenton, J. T. Hamm, L. S. Birnbaum, and G. L. Youngblood Persistent Abnormalities in the Rat Mammary Gland following Gestational and Lactational Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Toxicol. Sci., May 1, 2002; 67(1): 63 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Wolf, A. Hotchkiss, J. S. Ostby, G. A. LeBlanc, and L. E. Gray Jr. Effects of Prenatal Testosterone Propionate on the Sexual Development of Male and Female Rats: A Dose-Response Study Toxicol. Sci., January 1, 2002; 65(1): 71 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Benedict, T.-M. Lin, I. K. Loeffler, R. E. Peterson, and J. A. Flaws Physiological Role of the Aryl Hydrocarbon Receptor in Mouse Ovary Development Toxicol. Sci., August 1, 2000; 56(2): 382 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Dienhart, R. J. Sommer, R. E. Peterson, A. N. Hirshfield, and E. K. Silbergeld Gestational Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin Induces Developmental Defects in the Rat Vagina Toxicol. Sci., July 1, 2000; 56(1): 141 - 149. [Abstract] [Full Text] [PDF]
|
|