PMID- 36106461
OWN - NLM
STAT- MEDLINE
DCOM- 20221005
LR  - 20221027
IS  - 1520-5851 (Electronic)
IS  - 0013-936X (Linking)
VI  - 56
IP  - 19
DP  - 2022 Oct 4
TI  - 2,4-Dichlorophenol Increases Primordial Germ Cell Numbers via ESR2a-Dependent 
      Pathway in Zebrafish Larvae.
PG  - 13878-13887
LID - 10.1021/acs.est.2c05212 [doi]
AB  - Previous studies have reported the feminizing effects of 2,4-dichlorophenol 
      (2,4-DCP) on zebrafish (Danio rerio). However, the effect of 2,4-DCP on the 
      number of primordial germ cells (PGCs), an indicator for early sex 
      differentiation, remains elusive. In the present study, Tg (piwil1:egfp-UTR 
      nanos3) zebrafish (GFP-labeled PGCs) were treated with 2,4-DCP (10, 20, and 40 
      mug/L) from 5 to 15 days postfertilization to explore the effect on PGC numbers 
      and to elucidate associated molecular mechanisms. The results showed that 2,4-DCP 
      exposure increased PGC numbers, as evidenced by larger GFP fluorescent areas, 
      upregulated expressions of PGC marker genes (vasa and dnd), and raised the female 
      ratio. Notably, the mRNA level of estrogen receptor 2a (esr2a) was also increased 
      subsequently. Moreover, docking studies revealed stable 2,4-DCP interactions with 
      ESR2a, speculating a role of ESR2a signaling pathway in 2,4-DCP toxicity. 
      Furthermore, in esr2a knockout (esr2a(-/-)) zebrafish, the effects of 2,4-DCP 
      were considerably minimized, proving the involvement of the ESR2a signaling 
      pathway in the 2,4-DCP-mediated increase in PGC numbers. Dual-luciferase reporter 
      gene assay and point mutation studies demonstrated that 2,4-DCP-stimulated 
      promoter activity was mediated by estrogen response element (ERE) located in 
      -686/-674 of the vasa promoter and -731/-719 of the dnd promoter. Overall, 
      2,4-DCP can potentially enhance the expression of vasa and dnd by binding to 
      zebrafish ESR2a, thus leading to increased PGC numbers and subsequent 
      female-biased sex differentiation.
FAU - Hu, Yan
AU  - Hu Y
AD  - Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental 
      Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, People's 
      Republic of China.
FAU - Ma, Xuan
AU  - Ma X
AD  - Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental 
      Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, People's 
      Republic of China.
FAU - Liu, Rongjian
AU  - Liu R
AD  - Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental 
      Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, People's 
      Republic of China.
FAU - Mushtaq, Iqra
AU  - Mushtaq I
AD  - Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental 
      Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, People's 
      Republic of China.
FAU - Qi, Yongmei
AU  - Qi Y
AD  - Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental 
      Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, People's 
      Republic of China.
FAU - Yuan, Cong
AU  - Yuan C
AD  - Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental 
      Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, People's 
      Republic of China.
FAU - Huang, Dejun
AU  - Huang D
AUID- ORCID: 0000-0001-5497-6728
AD  - Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental 
      Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, People's 
      Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220915
PL  - United States
TA  - Environ Sci Technol
JT  - Environmental science & technology
JID - 0213155
RN  - 0 (Chlorophenols)
RN  - 0 (Estrogens)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Zebrafish Proteins)
RN  - 0 (sulfonated 2,4-dichlorophenol)
RN  - R669TG1950 (2,4-dichlorophenol)
SB  - IM
MH  - Animals
MH  - Cell Count
MH  - Chlorophenols
MH  - Estrogens/metabolism
MH  - Female
MH  - Germ Cells/metabolism
MH  - Larva/metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptors, Estrogen/metabolism
MH  - *Zebrafish/metabolism
MH  - *Zebrafish Proteins/genetics
OTO - NOTNLM
OT  - 2,4-DCP
OT  - Estrogen receptor signaling
OT  - Estrogenic effects
OT  - Molecular docking
OT  - Sex differentiation
EDAT- 2022/09/16 06:00
MHDA- 2022/10/06 06:00
CRDT- 2022/09/15 04:03
PHST- 2022/09/16 06:00 [pubmed]
PHST- 2022/10/06 06:00 [medline]
PHST- 2022/09/15 04:03 [entrez]
AID - 10.1021/acs.est.2c05212 [doi]
PST - ppublish
SO  - Environ Sci Technol. 2022 Oct 4;56(19):13878-13887. doi: 10.1021/acs.est.2c05212. 
      Epub 2022 Sep 15.