Triptonide is a reversible non-hormonal male contraceptive agent in mice and non-human primates
Zongliang Chang, Weibing Qin, Huili Zheng, Kathleen M. Schegg, Lu Han, Xiaohua Liu, Yue Wang, Zhuqing Wang, Hayden McSwiggin, Hongying Peng, Shuiqiao Yuan, Jiabao Wu, Yongxia Wang, Shenghui Zhu, Yanjia Jiang, Hua Nie, Yuan Tang, Yu Zhou, Michael J. M. Hitchcock, Yunge Tang, Wei Yan
Abstract
There are no non-hormonal male contraceptives currently on the market despite decades of efforts toward the development of "male pills". Here, we report that triptonide, a natural compound purified from the Chinese herb Tripterygium Wilfordii Hook F displays reversible male contraceptive effects in both mice and monkeys. Single daily oral doses of triptonide induces deformed sperm with minimal or no forward motility (close to 100% penetrance) and consequently male infertility in 3-4 and 5-6 weeks in mice and cynomolgus monkeys, respectively. Male fertility is regained in ~4-6 weeks after cessation of triptonide intake in both species. Either short- or long-term triptonide treatment causes no discernable systematic toxic side effects based on histological examination of vital organs in mice and hematological and serum biochemical analyses in monkeys. Triptonide appears to target junction plakoglobin and disrupts its interactions with SPEM1 during spermiogenesis. Our data further prove that targeting late spermiogenesis represents an effective strategy for developing non-hormonal male contraceptives.