Effects of in utero exposure to 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) on developmental landmarks, steroid hormone levels, and female estrous cyclicity in rats.
Previous studies have revealed that one of the major metabolites of PCBs detected in human blood, 4-OH-2,3,3',4',5-pentaCB (4-OH-CB107), accumulated in fetal liver, brain, and plasma and reduced maternal and fetal thyroid hormone levels after prenatal exposure to pregnant rats from gestational days (GD) 10-16. In the present study, the effects of 4-OH-CB-107 on developmental landmarks, steroid hormone levels, and estrous cyclicity of rat offspring after in utero exposure to 4-OH-CB107 was investigated. Pregnant rats were exposed to 0, 0.5, and 5.0 mg 4-OH-CB107 per kg bw from GD 10 to GD 16. Another group of rats was exposed to Aroclor 1254 (25 mg/kg bw) to study the differences between effects caused by parent PCB congeners and the 4-OH-CB107 alone. A significant, dose-dependent prolongation of the estrous cycle was observed in 75% and 82% of female offspring exposed to 0.5 and 5.0 mg 4-OH-PCB107, respectively, compared to 64% of Aroclor 1254 (25 mg/kg) exposed offspring. The diestrous stage of the estrous cycle was prolonged, resembling a state of pseudopregnancy, which might reflect early signs of reproductive senescence. Plasma estradiol concentrations in female rat offspring were significantly increased (50%) in the proestrous stage after exposure to 5 mg 4-OH-CB107 per kg bw. No effects on estradiol levels were observed in Aroclor 1254 treated animals. These results indicate that in utero exposure to 4-OH-CB107 leads to endocrine-disrupting effects, especially in female offspring. The possible impact on neurobehavior following exposure to 4-OH-CB107 will be reported elsewhere.
Meerts
Ilonka A T M
IA
Toxicology Group, Wageningen University, Wageningen, The Netherlands. ilonka.meerts@notox.nl
Hoving
Saske
S
van den Berg
Johannes H J
JH
Weijers
Bert M
BM
Swarts
Hans J
HJ
van der Beek
Eline M
EM
Bergman
Ake
A
Koeman
Jan H
JH
Brouwer
Abraham
A
D000284:Administration, Oral; D000818:Animals; D001140:Aroclors / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood*; D030762:Estrous Cycle / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005835:Genitalia / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D008297:Male; D018811:Maternal Exposure; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012741:Sexual Maturation / Q000187:drug effects*
C111120:2,3,3',4',5-pentachloro-4-hydroxybiphenyl; D001140:Aroclors; D004958:Estradiol; D011078:Polychlorinated Biphenyls