Effects of vertically transferred 3,3',4,4',5-pentachlorobiphenyl (PCB-126) on the reproductive development of female rats.
In order to study the effects of vertically transferred coplanar polychlorinated biphenyls on female reproductive development, female rat offspring from dams of Sprague-Dawley strain, which received daily oral administration of vehicle (corn oil) or 1 or 3 microg/kg of 3,3',4,4',5-pentachlorobiphenyl (PCB-126) from 2 weeks prior to mating with intact males until 20 days after delivery were examined from birth until puberty. Hepatic expression of the aryl hydrocarbon receptor (AhR)-inducible enzyme cytochrome P450 1A1 (CYP1A1) was detected in all offspring from PCB-126-exposed dams, indicating vertical transfer of PCB-126. Furthermore, quantification of ovarian mRNAs encoding CYP1A1, AhR and ARNT demonstrated that the ovary equipped the AhR-signaling system through which transcription of the CYP1A1 gene was enhanced in a dose-dependent manner. Exposure to PCB-126 retarded the growth of offspring in both exposed groups, while the viability of the neonates of the exposed groups was comparable to that of the oil-exposed controls. The exposure to 3 mug/kg/day reduced the ovarian weight on postnatal day (PND) 24, with atresia of most of the antral follicles and delayed vaginal opening. Exposure to 1 microg/kg/day did not produce such effects; however, both doses of PCB-126 induced external urogenital anomalies, such as vaginal thread and hypospadias, in all of the PCB-126-exposed female offspring. These results indicate that vertically transferred PCB-126 is potent enough to exert a direct effect on the ovary and adversely affect female puberty by altering the morphological and functional development of the female reproductive system.
Shirota
Mariko
M
Research Institute of Biosciences, Azabu University, Sagamihara, Kanagawa, Japan. shirota@azabu-u.ac.jp
Mukai
Motoko
M
Sakurada
Yosuke
Y
Doyama
Ari
A
Inoue
Kaoru
K
Haishima
Atsuko
A
Akahori
Fumiaki
F
Shirota
Kinji
K
D000818:Animals; D000831:Animals, Newborn; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D004965:Estrogen Antagonists / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D005836:Genitalia, Female / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010053:Ovary / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012741:Sexual Maturation / Q000187:drug effects / Q000502:physiology; D014599:Uterus / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D014621:Vagina / Q000002:abnormalities / Q000187:drug effects
D004965:Estrogen Antagonists; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; C023035:3,4,5,3',4'-pentachlorobiphenyl