PARENT SESSION
PLATFORM SESSION 14: REPRODUCTIVE TOXICOLOGY AND ENDOCRINE DISRUPTION
Chair: Hoyer, Patricia¹, ¹
Co-chair: Benedict, Jamie¹, ¹
Dover A-C
2:00 PM-4:00 PM

(252) EFFECT OF BENZO(a)PYRENE ON PLACENTATION.

Tomikawa, Junko¹, Yan, Junli¹, Ohgane, Jun¹, Hattori, Naka^1,2, Makino, Tsunehisa³, Tanaka, Satoshi¹, Shiota, Kunio¹, ¹ Animal Resource Science/Vet Med Science, Tokyo, JP² Bio-oriented Technology Research Advancement Institution, Saitama, JP³ Dept of Obstetrics and Gynecology, Kanagawa, JP

ABSTRACT- Benzo(a)pyrene (BaP) is a component of cigarette smoke. Little is known regarding the effects of BaP on development and function of placental tissues. To address this issue, we first injected pregnant mice with BaP at 1-10 mg/kg body weight on 6.5 and 7.5 days post coitum (dpc), and then examined concepti at 8.5 dpc. BaP-treated embryos were slightly smaller than those of untreated concepti. In situ hybridization analysis of placental tissues with trophoblast subtype-specific markers revealed that the number of spongiotrophoblast cells was markedly reduced in BaP-treated concepti compared with untreated controls. We also observed retarded postnatal growth of BaP-treated mice. Toxicity of BaP is considered to depend on metabolic bioactivation through the aryl hydrocarbon receptor (AhR) signaling pathway. In trophoblast stem (TS) cells, two species of AhR mRNA, approximately 4 and 6 kb in size, were detected by Northern hybridization analysis. Expression of 6 kb AhR mRNA was slightly up-regulated with differentiation of TS cells while the expression of 4 kb band, which presumably is alternatively spliced form, was constant throughout the culture both in proliferative and differentiaive conditions. Expression of cytochrome P450 1A1, a downstream gene of AhR signaling, was, however, induced in TS cells only in differentiaive condition but not in proliferative condition. TS cells thus did not respond to BaP under undifferentiating proliferative conditions. Moreover, despite the activation of AhR signaling in differentiated TS cells, expression patterns of several genetic markers for trophoblast subtypes were largely unaffected in BaP-treated TS cells. These results suggest that trophoblast stem cells have a mechanism repressing AhR function and that BaP action indirectly contributes to the abnormal early placental development in vivo. Such placental abnormality may in part cause developmental delay of fetuses.

KEY WORDS: Benzo(a)pyrene, Placentation, Trophoblast stem (TS) cells, Aryl hydrocarbon receptor