PMID- 19221147
OWN - NLM
STAT- MEDLINE
DCOM- 20090615
LR  - 20181201
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 108
IP  - 2
DP  - 2009 Apr
TI  - Proapoptotic effects of lindane on mouse primordial germ cells.
PG  - 445-51
LID - 10.1093/toxsci/kfp027 [doi]
AB  - Lindane (gamma-HCH) was examined for its effect on primordial germ cell (PGC) 
      development in the mouse embryo. We found that exposure by gavage of pregnant 
      mice to 15 or 30 mg/kg/bw lindane during the period of PGC migration and gonad 
      colonization (from 8.5 to 11.5 days post coitum, dpc) resulted in a significant 
      reduction of the number of germ cells within 12.5 dpc testis and ovaries (a 
      maximum of about 25 and 40%, respectively). Similarly, lindane caused a 
      dose-dependent decrease of the PGC number in an in vitro culture model. Further 
      experiments showed that in such model, lindane induced features of apoptotic cell 
      death in PGCs such as increase in caspase-3 activity, poly-ADP-ribose polymerase 
      cleavage, and terminal dUTP nick-end labeling (TUNEL) positivity. A marked 
      increase of the number of PGCs positive for TUNEL staining was also observed in 
      12.5 dpc gonads of embryos from pregnant mice subjected one day before to acute 
      lindane treatment (60 mg/kg/bw). Finally, we show that a brief incubation of 
      isolated PGCs with 10(-5)M lindane resulted in a marked decrease of the basal and 
      kit-ligand-induced phosphorylation level of the AKT kinase, known to be crucial 
      for PGC survival. Taken together these results demonstrate that embryo exposure 
      to lindane during early stages of gametogenesis can severely impair the number of 
      germ cells in the fetal gonads; the compound appears to affect PGC survival 
      through a direct proapoptotic action likely resulting from its adverse effect on 
      AKT activity in such cells.
FAU - La Sala, Gina
AU  - La Sala G
AD  - Department of Public Health and Cell Biology, Section of Histology and 
      Embryology, University of Rome Tor Vergata, Rome, Italy.
FAU - Farini, Donatella
AU  - Farini D
FAU - De Felici, Massimo
AU  - De Felici M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090216
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Antimetabolites)
RN  - 0 (Insecticides)
RN  - 59NEE7PCAB (Hexachlorocyclohexane)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - G34N38R2N1 (Bromodeoxyuridine)
SB  - IM
MH  - Animals
MH  - Antimetabolites
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Bromodeoxyuridine
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Gametogenesis/drug effects
MH  - Germ Cells/*drug effects
MH  - Hexachlorocyclohexane/*toxicity
MH  - In Situ Nick-End Labeling
MH  - Insecticides/*toxicity
MH  - Male
MH  - Mice
MH  - Oncogene Protein v-akt/biosynthesis/genetics
MH  - Pregnancy
EDAT- 2009/02/18 09:00
MHDA- 2009/06/16 09:00
CRDT- 2009/02/18 09:00
PHST- 2009/02/18 09:00 [entrez]
PHST- 2009/02/18 09:00 [pubmed]
PHST- 2009/06/16 09:00 [medline]
AID - kfp027 [pii]
AID - 10.1093/toxsci/kfp027 [doi]
PST - ppublish
SO  - Toxicol Sci. 2009 Apr;108(2):445-51. doi: 10.1093/toxsci/kfp027. Epub 2009 Feb 
      16.