PMID- 25241363
OWN - NLM
STAT- MEDLINE
DCOM- 20150127
LR  - 20211203
IS  - 1556-5653 (Electronic)
IS  - 0015-0282 (Linking)
VI  - 102
IP  - 5
DP  - 2014 Nov
TI  - Inhibition of mammalian target of rapamycin signaling pathway decreases retinoic 
      acid stimulated gene 8 expression in adult mouse testis.
PG  - 1482-1490.e3
LID - S0015-0282(14)02063-9 [pii]
LID - 10.1016/j.fertnstert.2014.08.004 [doi]
AB  - OBJECTIVE: To evaluate the expression of mammalian target of rapamycin (mTOR) 
      pathway molecules in mouse spermatogenesis and as well as its role during 
      proliferation and meiotic initiation of spermatogenic cells. DESIGN: Experimental 
      animal study. SETTING: University. ANIMAL(S): C57Balb-C adult male mice. 
      INTERVENTION(S): Expressions of mTOR signaling pathway proteins in adult testis 
      were evaluated. Then the effect of inhibition of this pathway on proliferation 
      and differentiation of spermatogonial stem cells was investigated using 
      seminiferous tubule culture. MAIN OUTCOME MEASURE(S): Immunohistochemistry was 
      performed to evaluate the expressions of mTOR signaling pathway proteins. To 
      inhibit mTOR signaling pathway by rapamycin, seminiferous tubule culture was 
      done. Viability assay and terminal deoxynucleotidyl transferase dUTP nick end 
      labeling was performed to evaluate the culture conditions and to examine cell 
      death, respectively. Western blot was used to determine the expressions of the 
      PCNA, STRA8, and VASA proteins. RESULT(S): Our results showed that spermatogonial 
      stem cells and preleptotene spermatocytes express total mTOR, p-mTOR, total 
      p70S6K, p-p70S6K, and p-4EBP1. Expressions of p-p70S6K, p-4EBP1, PCNA, and STRA8 
      decreased significantly in the rapamycin-treated group, where no difference was 
      observed in VASA expression. Cell viability and the number of apoptotic cells 
      were similar for all groups. CONCLUSION(S): Our findings suggest that the mTOR 
      signaling pathway may have role in the proliferation and stimulation of meiotic 
      initiation of spermatogonial stem cells. To the best of our knowledge, this is 
      the first ex vivo study that reports the function of the mTOR pathway in adult 
      mouse spermatogenesis.
CI  - Copyright (c) 2014 American Society for Reproductive Medicine. Published by 
      Elsevier Inc. All rights reserved.
FAU - Sahin, Pinar
AU  - Sahin P
AD  - Department of Histology and Embryology, Medical Faculty, Akdeniz University, 
      Campus, Antalya, Turkey.
FAU - Sahin, Zeliha
AU  - Sahin Z
AD  - Department of Histology and Embryology, Faculty of Medicine, Near East 
      University, Nicosia, Turkey.
FAU - Gungor-Ordueri, N Ece
AU  - Gungor-Ordueri NE
AD  - Department of Histology and Embryology, Medical Faculty, Akdeniz University, 
      Campus, Antalya, Turkey.
FAU - Donmez, Baris Ozgur
AU  - Donmez BO
AD  - School of Health, Akdeniz University, Campus, Antalya, Turkey.
FAU - Celik-Ozenci, Ciler
AU  - Celik-Ozenci C
AD  - Department of Histology and Embryology, Medical Faculty, Akdeniz University, 
      Campus, Antalya, Turkey. Electronic address: cilerozenci@akdeniz.edu.tr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140917
PL  - United States
TA  - Fertil Steril
JT  - Fertility and sterility
JID - 0372772
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Stra8 protein, mouse)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*metabolism
MH  - Animals
MH  - Cell Division/drug effects/physiology
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Signal Transduction/drug effects/*physiology
MH  - Spermatogenesis/drug effects/*physiology
MH  - Spermatozoa/*cytology/drug effects/*physiology
MH  - TOR Serine-Threonine Kinases/*metabolism/pharmacology
MH  - Testis/*metabolism
OTO - NOTNLM
OT  - STRA8
OT  - mTOR
OT  - rapamycin
OT  - seminiferous tubule culture
EDAT- 2014/09/23 06:00
MHDA- 2015/01/28 06:00
CRDT- 2014/09/22 06:00
PHST- 2014/03/31 00:00 [received]
PHST- 2014/07/07 00:00 [revised]
PHST- 2014/08/01 00:00 [accepted]
PHST- 2014/09/22 06:00 [entrez]
PHST- 2014/09/23 06:00 [pubmed]
PHST- 2015/01/28 06:00 [medline]
AID - S0015-0282(14)02063-9 [pii]
AID - 10.1016/j.fertnstert.2014.08.004 [doi]
PST - ppublish
SO  - Fertil Steril. 2014 Nov;102(5):1482-1490.e3. doi: 
      10.1016/j.fertnstert.2014.08.004. Epub 2014 Sep 17.