Effects of tamoxifen citrate on gene expression during nuclear chromatin condensation in male rats.
OBJECTIVE
To evaluate the effects of tamoxifen citrate on gene expression during nuclear chromatin condensation in male rats.


METHODS
The effects of an oral dose of 0.4 kg/(kg.d) tamoxifen citrate on rates of in vitro chromatin decondensation, acridine orange (AO) dye uptake, concentration of thiol-groups, levels and/or expression of transition proteins 1, 2 (TP1, TP2), protamine 1 (P1), cyclic AMP response element modulator-tau (CREMtau), androgen-binding protein (ABP) and cyclic adenosine 3',5' monophosphate (cAMP) were evaluated after 60 days of exposure in adult male rats. Controls received the vehicle.


RESULTS
Tamoxifen citrate enhanced the rates of chromatin decondensation, increased AO dye uptake and reduced free thiols in caput epididymal sperms and reduced the levels of TP1, TP2, P1, and CREMtau in the testis, while cAMP was unaffected. P1 deposition was absent in the sperm. The transcripts of TP1, TP2 were increased, of P1 and ABP decreased, while those of CREMtau unaffected in the testis.


CONCLUSIONS
Tamoxifen citrate reduced caput epididymal sperm chromatin compaction by reducing the testicular levels of proteins TP1, TP2 and P1 and the CREMtau involved in chromatin condensation during spermiogenesis. Tamoxifen citrate affects the expression of these genes at both the transcriptional and post-transcriptional levels.
Aleem
Mukhtar
M
Department of Neuroendocrinology, National Institute for Research in Reproductive Health (ICMR), J. M. Street, Parel, Mumbai 400012, India.
Padwal
Varsha
V
Choudhari
Jyoti
J
Balasinor
Nafisa
N
Parte
Priyanka
P
Gill-Sharma
Manjeet
M
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013091:Spermatogenesis; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D013737:Testis / Q000378:metabolism / Q000648:ultrastructure
D002843:Chromatin; D017931:DNA Primers; D013438:Sulfhydryl Compounds; D013629:Tamoxifen; D000242:Cyclic AMP