1. Academic Validation
  2. Triptonide is a reversible non-hormonal male contraceptive agent in mice and non-human primates

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

  • Nat Commun. 2021 Feb 23;12(1):1253. doi: 10.1038/s41467-021-21517-5.
Zongliang Chang  # 1 Weibing Qin  # 2 3 Huili Zheng  # 1 Kathleen Schegg  # 1 Lu Han 2 3 Xiaohua Liu 2 3 Yue Wang 1 Zhuqing Wang 1 Hayden McSwiggin 1 Hongying Peng 1 Shuiqiao Yuan 1 Jiabao Wu 2 3 Yongxia Wang 2 3 Shenghui Zhu 2 3 Yanjia Jiang 2 3 Hua Nie 2 3 Yuan Tang 2 3 Yu Zhou 2 3 Michael J M Hitchcock 4 Yunge Tang 5 6 Wei Yan 7 8 9
Affiliations

Affiliations

  • 1 Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA.
  • 2 NHC Key Laboratory of Male Reproduction and Genetics, Guangzhou, People's Republic of China.
  • 3 Family Planning Research Institute of Guangdong Province, Guangzhou, People's Republic of China.
  • 4 Department of Microbiology and Immunology, University of Nevada, Reno School of Medicine, Reno, NV, USA.
  • 5 NHC Key Laboratory of Male Reproduction and Genetics, Guangzhou, People's Republic of China. [email protected].
  • 6 Family Planning Research Institute of Guangdong Province, Guangzhou, People's Republic of China. [email protected].
  • 7 Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA. [email protected].
  • 8 The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA. [email protected].
  • 9 Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. [email protected].
  • # Contributed equally.
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.

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