PMID- 30336312
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20181211
IS  - 1879-1298 (Electronic)
IS  - 0045-6535 (Linking)
VI  - 215
DP  - 2019 Jan
TI  - Maternal di-(2-ethylhexyl) phthalate exposure inhibits cerebellar granule 
      precursor cell proliferation via down-regulating the Shh signaling pathway in 
      male offspring.
PG  - 313-322
LID - S0045-6535(18)31894-0 [pii]
LID - 10.1016/j.chemosphere.2018.10.040 [doi]
AB  - Di-(2-ethylhexyl) phthalate (DEHP) is an endocrine disrupting chemical (EDC) 
      widely used as a plasticizer in many materials. Epidemiological investigations 
      have shown that DEHP exposure during early development is related to 
      cerebellar-related adverse neurodevelopmental outcomes. However, animal studies 
      involving the effect of DEHP exposure on cerebellar development have rarely been 
      reported and the potential mechanisms are unclear. The aim of this study was to 
      investigate the effect of maternal DEHP exposure on the proliferation of 
      cerebellar granule cell precursor cells (GCPs) and the mechanisms involved. 
      Wistar rats were randomly assigned to four exposure groups and given 0, 30, 300, 
      or 750 mg/kg/d DEHP by intragastric administration from gestational day (GD) 0 to 
      postnatal day (PN) 21. Exposure to 300 and 750 mg/kg/d DEHP restrained GCPs 
      proliferation and impaired neurodevelopment for males. Furthermore, exposure to 
      300 and 750 mg/kg/d DEHP decreased male pups protein expressions and mRNA levels 
      of molecules related to proliferation, including Shh, Gli1, N-Myc, CyclinD1. In 
      addition, the estrogen level and aromatase expression also reduced in male pups 
      after maternal exposure to DEHP. However, effects on females were not obvious. 
      These results suggested that 300 and 750 mg/kg/d DEHP exposure inhibit the 
      proliferation of GCPs in male offspring and ultimately contribute to the 
      impairment of neuromotor development. This, may be caused by the down-regulation 
      of Shh signaling. And the susceptibility of male offspring to DEHP exposure may 
      be attributed to the decreased estrogen level and aromatase expression in male 
      pup's cerebellum.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Fu, Yuanyuan
AU  - Fu Y
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      China Medical University, No. 77 Puhe Road, Shenyang 110122, PR China.
FAU - Dong, Jing
AU  - Dong J
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      China Medical University, No. 77 Puhe Road, Shenyang 110122, PR China.
FAU - You, Mingdan
AU  - You M
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      China Medical University, No. 77 Puhe Road, Shenyang 110122, PR China.
FAU - Cong, Zhangzhao
AU  - Cong Z
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      China Medical University, No. 77 Puhe Road, Shenyang 110122, PR China.
FAU - Wei, Lingling
AU  - Wei L
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      China Medical University, No. 77 Puhe Road, Shenyang 110122, PR China.
FAU - Fu, Hui
AU  - Fu H
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      China Medical University, No. 77 Puhe Road, Shenyang 110122, PR China.
FAU - Wang, Yi
AU  - Wang Y
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      China Medical University, No. 77 Puhe Road, Shenyang 110122, PR China.
FAU - Wang, Yuan
AU  - Wang Y
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      China Medical University, No. 77 Puhe Road, Shenyang 110122, PR China.
FAU - Chen, Jie
AU  - Chen J
AD  - Department of Occupational and Environmental Health, School of Public Health, 
      China Medical University, No. 77 Puhe Road, Shenyang 110122, PR China. Electronic 
      address: jchen@cmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20181009
PL  - England
TA  - Chemosphere
JT  - Chemosphere
JID - 0320657
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Plasticizers)
RN  - C42K0PH13C (Diethylhexyl Phthalate)
SB  - IM
MH  - Animals
MH  - *Cell Proliferation
MH  - Cerebellum/metabolism/*pathology
MH  - Diethylhexyl Phthalate/*toxicity
MH  - Endocrine Disruptors/toxicity
MH  - Female
MH  - Hedgehog Proteins/*metabolism
MH  - Male
MH  - *Maternal Exposure
MH  - Plasticizers/toxicity
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*metabolism
MH  - Rats
MH  - Rats, Wistar
OTO - NOTNLM
OT  - Cerebellum
OT  - DEHP
OT  - EDCs
OT  - Granule cell precursor
OT  - Proliferation
EDAT- 2018/10/20 06:00
MHDA- 2018/12/12 06:00
CRDT- 2018/10/19 06:00
PHST- 2018/06/07 00:00 [received]
PHST- 2018/10/04 00:00 [revised]
PHST- 2018/10/06 00:00 [accepted]
PHST- 2018/10/20 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2018/10/19 06:00 [entrez]
AID - S0045-6535(18)31894-0 [pii]
AID - 10.1016/j.chemosphere.2018.10.040 [doi]
PST - ppublish
SO  - Chemosphere. 2019 Jan;215:313-322. doi: 10.1016/j.chemosphere.2018.10.040. Epub 
      2018 Oct 9.