Meeting Men's Contraceptive Needs – Long-Term Oral-Administered Retinoic Acid Receptor Antagonist Inhibits Spermatogenesis in Mice with a Reversible and Rapid Recovery

2011 ◽  
pp. LB-4-LB-4
Author(s):  
Sanny SW Chung ◽  
Xiangyuan Wang ◽  
Debra J Wolgemuth
Keyword(s):  
Retinoic Acid ◽  
Receptor Antagonist ◽  
Retinoic Acid Receptor ◽  
Rapid Recovery ◽  
Acid Receptor

scholarly journals Prolonged Oral Administration of a Pan-Retinoic Acid Receptor Antagonist Inhibits Spermatogenesis in Mice With a Rapid Recovery and Changes in the Expression of Influx and Efflux Transporters

Endocrinology ◽  
2016 ◽  
Vol 157 (4) ◽  
pp. 1601-1612 ◽  
Author(s):  
Sanny S. W. Chung ◽  
Xiangyuan Wang ◽  
Debra J. Wolgemuth
Keyword(s):  
Retinoic Acid ◽  
Oral Administration ◽  
Receptor Antagonist ◽  
Retinoic Acid Receptor ◽  
Rapid Recovery ◽  
Acid Receptor ◽  
Treatment Regimens ◽  
Testicular Weight ◽  
Testicular Histology ◽  
Restoration Of Fertility

Abstract We have previously shown that oral administration of a pan-retinoic acid receptor antagonist in mice daily at 2.5 mg/kg for 4 weeks reversibly inhibited spermatogenesis, with no detectable side effects. To elucidate the lowest dose and the longest dosing regimen that inhibits spermatogenesis but results in complete restoration of fertility upon cessation of administration of the drug, we examined the effects of daily doses as low as 1.0 mg/kg with dosing periods of 4, 8, and 16 weeks. We observed 100% sterility in all regimens, with restoration of fertility upon cessation of the drug treatment even for as long as 16 weeks. There was no change in testosterone levels in these males and the progeny examined from 2 of the recovered males were healthy and fertile, with normal testicular weight and testicular histology. Strikingly, a more rapid recovery, as assessed by mating studies, was observed at the lower dose and longer dosing periods. Insight into possible mechanisms underlying this rapid recovery was obtained at 2 levels. First, histological examination revealed that spermatogenesis was not as severely disrupted at the lower dose and with the longer treatment regimens. Second, gene expression analysis revealed that the more rapid recovery may involve the interplay of ATP-binding cassette efflux and solute carrier influx transporters in the testes.

scholarly journals Oral Administration of a Retinoic Acid Receptor Antagonist Reversibly Inhibits Spermatogenesis in Mice

Endocrinology ◽  
2011 ◽  
Vol 152 (6) ◽  
pp. 2492-2502 ◽  
Author(s):  
Sanny S. W. Chung ◽  
Xiangyuan Wang ◽  
Shelby S. Roberts ◽  
Stephen M. Griffey ◽  
Peter R. Reczek ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Oral Administration ◽  
Receptor Antagonist ◽  
Retinoic Acid Receptor ◽  
Acid Receptor

A Widely Used Retinoic Acid Receptor Antagonist Induces Peroxisome Proliferator-Activated Receptor-γ Activity

2007 ◽  
Vol 71 (5) ◽  
pp. 1251-1257 ◽  
Author(s):  
Michael Schupp ◽  
Joshua C. Curtin ◽  
Roy J. Kim ◽  
Andrew N. Billin ◽  
Mitchell A. Lazar
Keyword(s):  
Retinoic Acid ◽  
Receptor Antagonist ◽  
Retinoic Acid Receptor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Acid Receptor

Retinoic acid receptor antagonist LE540 attenuates wakefulness via the dopamine D1 receptor in mice

2011 ◽  
Vol 1423 ◽  
pp. 10-16 ◽  
Author(s):  
Kazuyoshi Kitaoka ◽  
Mika Shimizu ◽  
Noriyuki Shimizu ◽  
Sachiko Chikahisa ◽  
Madoka Nakagomi ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Receptor Antagonist ◽  
Retinoic Acid Receptor ◽  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Acid Receptor
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