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T3 preserves ovarian granulosa cells from chemotherapy induced apoptosis.
MedLine Citation:
PMID:  22911894     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Infertility is a dramatic and frequent side effect in women who are undergoing chemotherapy. Actual strategies are mainly focused on oocytes cryopreservation, but this is not always a suitable option. Considering the key role that granulosa cells play in follicles life, we study if thyroid hormone T3 protects rat ovarian granulosa cells from chemotherapy-induced apoptosis.To this aim a cell line was established from fresh isolated rat granulosa cells and named rGROV. Cells were exposed to Paclitaxel and T3 and, apoptosis, cell viability and cell cycle distribution were analyzed under different conditions. Firstly, the integrity of the steroidogenic pathway was demonstrated, and the presence of thyroid receptors, transporters and deiodinases was confirmed by QPCR. Cells were then exposed to Paclitaxel (Ptx) alone or contemporary to T3. MTT and Tunel assays revealed that while there was a relevant percentage of dying cells when exposed to Ptx (40-60%), the percentage was sensibly reduced (20-30%) in favour of living cells, if T3 was present. Cell cycle analysis showed that cells exposed to Ptx alone were firstly collected in G2 and then dyed by apoptosis; on the other hand the T3 granted the cells to cycle regularly and survive Ptx insult. In addition Western blot and FCM analyses confirmed that caspases activation, casp3 and Bax were downregulated by T3 and that Bcl 2 and cyclins A, B together with cdk1 were upregulated by T3.In conclusions we demonstrated that thyroid hormone T3 can counteract the lethal effect of taxol on granulosa cells.
Authors:
Cecilia Verga Falzacappa; Eleonora Timperi; Barbara Bucci; Donatella Amendola; Piero Piergrossi; Davide D'Amico; Mariagiulia Santaguida; Marco Centanni; Silvia Misiti
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-21
Journal Detail:
Title:  The Journal of endocrinology     Volume:  -     ISSN:  1479-6805     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
C Verga Falzacappa, Experimental Medicine, Sapienza University of Rome, Rome, Italy.
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