Contraceptives, also known as birth controls, are extremely important in reducing unintended pregnancies and abortions, as well as improving maternal health and decreasing infant mortality. Oral contraceptive pills, in particular, are especially popular due to their convenience and non-invasiveness. However, they are currently only available for women, which begs the question: where are the pills for men? There have been many efforts in developing male oral contraceptive pills that can suppress sperm production, but they are often met with an undesirable, yet prevailing, problem: testis shrinkage. While there have been reports of a potential hormonal oral pill for men, they still come with many side effects such as weight gain and loss of sex drive. Therefore, the market of male oral pills is still very scarce and unexplored.
Recently, a group of scientists from the US and China reported the discovery of a compound that, rather than suppressing sperm production altogether, disables the function of sperm in mice and monkeys. The compound, known as triptonide, was purified from a Chinese herb called Tripterygium Wilfordii Hook F, which had been previously shown to cause infertility in patients. It turned out that triptonide, when fed to mice and monkeys, caused sperm to deform and thus lose their function. This effect could be sustained for months with no obvious toxicity or side effects for the animals. Importantly, the effect was also reversible; when the animals stopped taking the compound, their fertility was regained after a few weeks. Therefore, triptonide’s efficient, reversible, and non-toxic ability to deform and inactivate sperm proved its potential as a male contraceptive drug candidate.
The researchers next sought to figure out how triptonide inactivated sperms. They tested the compound’s ability to bind against every single protein found in the mice’s testis, and discovered that triptonide was able to bind to a protein called junction plakoglobin (JUP). JUP is a protein that interacts and helps with other key proteins in the sperm during the final stages of sperm cell development, also known as spermiogenesis. Thus, binding to JUP disrupts its function, which also affects the other critical proteins during sperm cell development, ultimately resulting in a defect in the final produced sperm cell. This discovery not only shed light on the mechanism of triptonide, but also opened up a whole new possibility of male contraceptives: we now know that, in addition to the conventional approach of suppressing sperm production, targeting spermiogenesis may be a viable method for future drug development.
Overall, this study presented triptonide as a promising male contraceptive drug candidate. Even though this compound is yet to be tested in humans, the results from this paper were still useful in confirming the approach of disabling sperms, rather than suppressing sperm production, for male contraceptives. This could potentially expand the areas of research and development for male oral contraceptive pills. Currently, the burden of contraception lies mostly on women, which unfairly forces women to assume the brunt of any financial, health-related, or social stresses that may come with contraception. With a promising drug candidate for a male oral pill in sight, a future with a more just contraceptive arrangement may be closer.
Three of the co-authors, Zong-liang Chang, Huili Zheng, and Kathleen Schegg, are from the University of Nevada. Zong-liang Chang was a graduate student, Huili Zheng is a research assistant professor, while Kathleen Schegg is a research biochemist. Weibing Qin, another co-author of the paper, is an associate professor from the NHC Key Laboratory of Male Reproduction and Genetics at Guangzhou, China.
Managing Correspondent: Wei Li
Press Article: Natural compound exhibits almost ideal male contraceptive effects in pre-clinical studies, Medical Xpress.
Nature: New compound for male contraceptive pill, ScienceDaily.
Original Article: Triptonide is a reversible non-hormonal male contraceptive agent in mice and non-human primates, Nature Communications.