PMID- 10543027
OWN - NLM
STAT- MEDLINE
DCOM- 19991202
LR  - 20190513
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 51
IP  - 2
DP  - 1999 Oct
TI  - Gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) severely 
      alters reproductive function of female hamster offspring.
PG  - 259-64
AB  - 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.
FAU - Wolf, C J
AU  - Wolf CJ
AD  - Endocrinology Branch, US Environmental Protection Agency, Research Triangle Park, 
      North Carolina 27711, USA.
FAU - Ostby, J S
AU  - Ostby JS
FAU - Gray, L E Jr
AU  - Gray LE Jr
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Teratogens)
SB  - IM
MH  - Animals
MH  - Animals, Newborn/growth & development/*physiology
MH  - Cricetinae
MH  - Dose-Response Relationship, Drug
MH  - Embryo Implantation/drug effects
MH  - Estrus/drug effects
MH  - Female
MH  - Fertility/drug effects
MH  - Growth/drug effects
MH  - Litter Size/drug effects
MH  - Male
MH  - Mesocricetus
MH  - Polychlorinated Dibenzodioxins/*toxicity
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Reproduction/*drug effects
MH  - Sexual Behavior, Animal/drug effects
MH  - Sexual Maturation/drug effects
MH  - Teratogens/*toxicity
MH  - Vagina/drug effects/growth & development
EDAT- 1999/10/30 09:00
MHDA- 2001/03/28 10:01
CRDT- 1999/10/30 09:00
PHST- 1999/10/30 09:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/10/30 09:00 [entrez]
AID - 10.1093/toxsci/51.2.259 [doi]
PST - ppublish
SO  - Toxicol Sci. 1999 Oct;51(2):259-64. doi: 10.1093/toxsci/51.2.259.