PMID- 22505044
OWN - NLM
STAT- MEDLINE
DCOM- 20121113
LR  - 20191210
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 128
IP  - 1
DP  - 2012 Jul
TI  - Staying alive: PI3K pathway promotes primordial follicle activation and survival 
      in response to 3MC-induced ovotoxicity.
PG  - 258-71
LID - 10.1093/toxsci/kfs137 [doi]
AB  - 3-Methylcholanthrene (3MC) is a potent ovotoxicant capable of causing premature 
      ovarian failure through primordial follicle depletion. Despite 3MCs ovotoxicity 
      having been established for 30 years, relatively little information exists on the 
      mechanisms. In this study, we examined the effects of 3MC exposure on the 
      immature ovarian follicle population. Microarray analysis revealed a complex 
      mechanism of 3MC-induced ovotoxicity involving a number of cellular processes 
      associated with xenobiotic metabolism, ovarian cancer, cell cycle progression, 
      and cell death. 3MC exposure was also found to induce developing follicle atresia 
      and aberrant primordial follicle activation via the stimulation of PI3K/Akt and 
      mammalian target of rapamycin (mTOR) signaling pathways. Inhibition of PI3K/Akt 
      signaling resulted in the severe depletion of the primordial follicle pool, with 
      further analysis identifying increased Akt1-stimulated Bad phosphoinhibition in 
      3MC-treated primordial follicles. Our results suggest that the primordial 
      follicle pool enters a "prosurvival" state upon 3MC exposure and that its 
      depletion is due to a vicious cycle of primordial follicle activation in an 
      attempt to replace developing follicles undergoing follicular atresia.
FAU - Sobinoff, Alexander P
AU  - Sobinoff AP
AD  - Reproductive Science Group, School of Environmental & Life Sciences, University 
      of Newcastle, Callaghan, New South Wales 2308, Australia.
FAU - Nixon, Brett
AU  - Nixon B
FAU - Roman, Shaun D
AU  - Roman SD
FAU - McLaughlin, Eileen A
AU  - McLaughlin EA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
DEP - 20120412
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 56-49-5 (Methylcholanthrene)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Female
MH  - Methylcholanthrene/*toxicity
MH  - Mice
MH  - Ovarian Follicle/*drug effects/enzymology/metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Polymerase Chain Reaction
MH  - Real-Time Polymerase Chain Reaction
MH  - Transcriptome
MH  - Up-Regulation
EDAT- 2012/04/17 06:00
MHDA- 2012/11/14 06:00
CRDT- 2012/04/17 06:00
PHST- 2012/04/17 06:00 [entrez]
PHST- 2012/04/17 06:00 [pubmed]
PHST- 2012/11/14 06:00 [medline]
AID - kfs137 [pii]
AID - 10.1093/toxsci/kfs137 [doi]
PST - ppublish
SO  - Toxicol Sci. 2012 Jul;128(1):258-71. doi: 10.1093/toxsci/kfs137. Epub 2012 Apr 
      12.