| Info. | Vol.10 - No.3 (2016.09.20) |
|---|---|
| Title | Parenteral Exposure to DEHP and Its Effect on the Microstructure of Bone and Wnt Signaling Pathway in F2 Female Mice |
| Authors | Keun Young Cheon1, Ki Hyun Kil1, Jung In Choi1, Ra Yon Kim1, Mee Ran Kim1, Jang Heub Kim1 & Hyun Hee Cho1,* |
| Institutions | 1Department of Ob/Gyn, 9th floor of Seoul St. Mary?셲 Hospital, Catholic University Medical College, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea *Correspondence and requests for materials should be addressed to H.H. Cho ( drrabbit@catholic.ac.kr) |
| Abstract | Diethylhexyl phthalate (DEHP) is a widely used plasticizer, and its exposure via the enteral and parenteral routes can affect estrogen function and has transgenerational effect. The bones are the most important target organs for estrogen; however, the related gene pathway and the effects of DEHP on bones remain unknown. In this study, we evaluated whether parenteral exposure to DEHP has effects on bone microarchitecture in F2 mice, and determined the related gene pathway. Pregnant mice (F0) were exposed to DEHP, at doses of 30 關g/kg/day (low dose) and 400 關g/kg/day (high dose), and corn oil during pregnancy and lactation. F2 siblings were not treated with DEHP. We performed micro-CT to analyze the microstructure of the tibial head and microarray analysis on ovary cells from F2 female siblings of 17-18 weeks of age to evaluate the gene expression. The percentage of bone volume in the low- (5.55%짹0.85%) and high-dose (7.09%짹4.15%) groups was higher than that in the control (2.25%짹1.22%; P<0.05). Trabecular number (per mm2) was higher in the low- (0.87짹0.12) and high-dose (0.95짹0.55) groups compared to that in the control (0.37짹0.21; P<0.05). Trabecular thickness was greater in the high-dose group (0.073짹0.006 關m) than in the control (0.060짹0.002 關m) and low-dose (0.063짹0.004 關m) groups. The structure model index (SMI) of the low- and high-dose groups was significantly lower than the corresponding value in the control group (P<0.05). Micro-CT analysis indicated proliferative changes in trabecular bone in the treated F2 siblings. In the microarray analysis of ovary cells, CTNNB1 (catenin beta 1) and PPP3R1 gene expressions were significantly modified in the low- and high-dose groups. SFRP1, DVL2, WNT11, and WNT16 showed significant expression changes in the low-dose group, but not in the high-dose group. Taken together, parenteral exposure to DEHP during pregnancy and lactation could influence the trabecular bone microarchitectures of F2 siblings and affect certain genes associated with the Wnt signaling pathway. |
| Keyword | DEHP, Parenteral exposure, Bone microstructure, WNT pathway, Microarray |
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