PMID- 19038859
OWN - NLM
STAT- MEDLINE
DCOM- 20090625
LR  - 20211020
IS  - 0006-3363 (Print)
IS  - 1529-7268 (Electronic)
IS  - 0006-3363 (Linking)
VI  - 80
IP  - 3
DP  - 2009 Mar
TI  - TNF alpha-mediated disruption of spermatogenesis in response to Sertoli cell 
      injury in rodents is partially regulated by MMP2.
PG  - 581-9
LID - 10.1095/biolreprod.108.073122 [doi]
AB  - Mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell injury in peripubertal 
      rodents results in the stimulation of germ cell apoptosis through an interaction 
      of FAS/FASL between these two cell types. During this peripubertal period, an 
      early spike in the incidence of germ cell apoptosis occurs during the first wave 
      of spermatogenesis and is essential for the development of functional 
      spermatogenesis in adults. Our previous observations revealed that soluble tumor 
      necrosis factor alpha (sTNFA) released by germ cells after MEHP exposure 
      consequently resulted in a robust induction of FASL by Sertoli cells. 
      Metalloproteinases (MPs) are essential for processing the TNFA precursor to its 
      soluble form and its ability to bind to TNFRSF1A. The activity of MPs is 
      regulated by the tissue inhibitors of MPs (TIMPs) family. Herein we report that 
      TIMP2 is predominately expressed in Sertoli cells and that protein levels 
      decrease in a time-dependent manner after MEHP exposure. The secretion of matrix 
      MP 2 (MMP2) in primary rat Sertoli cell-germ cell cocultures is induced after 
      MEHP exposure, and its activity increases in a time-dependent manner. The 
      addition of SB-3CT, a specific gelatinase inhibitor, decreases the activity of 
      MMP2 and significantly reduces MEHP-enhanced sTNFA production in primary 
      cocultures. In vivo challenges with SB-3CT decrease sTNFA and reduce MEHP-induced 
      testicular germ cell apoptosis. In primary cocultures, MEHP exposure causes a 
      9.46-fold increase in sTNFA, while the addition of recombinant MMP2 protein 
      results in a 5.4-fold increase in sTNFA, suggesting that MEHP-induced MMP2 is in 
      part responsible for the activation of TNFA in the testis. Taken together, these 
      observations indicate the distinct role of specific MPs in response to 
      toxicant-induced Sertoli cell injury, providing further insights into the 
      mechanism by which Sertoli cells control the sensitivity of germ cells to undergo 
      apoptosis.
FAU - Yao, Pei-Li
AU  - Yao PL
AD  - The Institute for Cellular and Molecular Biology, University of Texas at Austin, 
      Austin, Texas 78712-1074, USA.
FAU - Lin, Yi-Chen
AU  - Lin YC
FAU - Richburg, John H
AU  - Richburg JH
LA  - eng
GR  - P30 ES007784/ES/NIEHS NIH HHS/United States
GR  - ES009145/ES/NIEHS NIH HHS/United States
GR  - ES007784/ES/NIEHS NIH HHS/United States
GR  - R01 ES009145/ES/NIEHS NIH HHS/United States
GR  - R01 ES016591/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20081126
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (Heterocyclic Compounds, 1-Ring)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (SB 3CT compound)
RN  - 0 (Sulfones)
RN  - 0 (Tnfrsf1a protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - 147257-52-1 (Nfkb1 protein, mouse)
RN  - C42K0PH13C (Diethylhexyl Phthalate)
RN  - EC 3.4.24.- (Gelatinases)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - FU2EWB60RT (mono-(2-ethylhexyl)phthalate)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Diethylhexyl Phthalate/*analogs & derivatives/pharmacology
MH  - Gelatinases/antagonists & inhibitors
MH  - Heterocyclic Compounds, 1-Ring/pharmacology
MH  - Male
MH  - Matrix Metalloproteinase 2/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B p50 Subunit/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I/metabolism
MH  - Sertoli Cells/cytology/*drug effects/*metabolism
MH  - Signal Transduction/physiology
MH  - Spermatogenesis/*physiology
MH  - Sulfones/pharmacology
MH  - Testis/cytology/drug effects/metabolism
MH  - Tissue Inhibitor of Metalloproteinase-2/metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
PMC - PMC2805399
EDAT- 2008/11/29 09:00
MHDA- 2009/06/26 09:00
PMCR- 2010/03/01
CRDT- 2008/11/29 09:00
PHST- 2008/11/29 09:00 [pubmed]
PHST- 2009/06/26 09:00 [medline]
PHST- 2008/11/29 09:00 [entrez]
PHST- 2010/03/01 00:00 [pmc-release]
AID - biolreprod.108.073122 [pii]
AID - 10.1095/biolreprod.108.073122 [doi]
PST - ppublish
SO  - Biol Reprod. 2009 Mar;80(3):581-9. doi: 10.1095/biolreprod.108.073122. Epub 2008 
      Nov 26.