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

• DOI: 10.1038/s41467-021-21517-5
• Publication Date: 2021-02-23T11:14:21Z
• Authors: 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. Hit...; Yunge Tang; Wei Yan
• Keywords: Male contraceptive; Vasectomy; Hormonal contraception; Male fertility

Abstract There are no non-hormonal male contraceptives currently on the market despite decades of efforts toward development “male pills”. Here, we report that triptonide, a natural compound purified from Chinese herb Tripterygium Wilfordii Hook F displays reversible contraceptive effects in both mice and monkeys. Single daily oral doses triptonide induces deformed sperm with minimal or forward motility (close to 100% penetrance) consequently infertility 3–4 5–6 weeks cynomolgus monkeys, respectively. Male fertility is regained ~4–6 after cessation intake species. Either short- long-term treatment causes discernable systematic toxic side based histological examination vital organs hematological serum biochemical analyses Triptonide appears target junction plakoglobin disrupts its interactions SPEM1 during spermiogenesis. Our data further prove targeting late spermiogenesis represents an effective strategy for developing contraceptives.