Triptonide is a reversible non-hormonal male contraceptive agent in mice and non-human primates

Zongliang Chang, Weibing Qin, Huili Zheng, Kathleen 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 () and Wei Yan ()
Additional contact information
Zongliang Chang: University of Nevada, Reno School of Medicine
Weibing Qin: NHC Key Laboratory of Male Reproduction and Genetics
Huili Zheng: University of Nevada, Reno School of Medicine
Kathleen Schegg: University of Nevada, Reno School of Medicine
Lu Han: NHC Key Laboratory of Male Reproduction and Genetics
Xiaohua Liu: NHC Key Laboratory of Male Reproduction and Genetics
Yue Wang: University of Nevada, Reno School of Medicine
Zhuqing Wang: University of Nevada, Reno School of Medicine
Hayden McSwiggin: University of Nevada, Reno School of Medicine
Hongying Peng: University of Nevada, Reno School of Medicine
Shuiqiao Yuan: University of Nevada, Reno School of Medicine
Jiabao Wu: NHC Key Laboratory of Male Reproduction and Genetics
Yongxia Wang: NHC Key Laboratory of Male Reproduction and Genetics
Shenghui Zhu: NHC Key Laboratory of Male Reproduction and Genetics
Yanjia Jiang: NHC Key Laboratory of Male Reproduction and Genetics
Hua Nie: NHC Key Laboratory of Male Reproduction and Genetics
Yuan Tang: NHC Key Laboratory of Male Reproduction and Genetics
Yu Zhou: NHC Key Laboratory of Male Reproduction and Genetics
Michael J. M. Hitchcock: University of Nevada, Reno School of Medicine
Yunge Tang: NHC Key Laboratory of Male Reproduction and Genetics
Wei Yan: University of Nevada, Reno School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21517-5

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