The story of male hormonal contraceptives is one of small steps forward and big steps back because, although for centuries science has focused almost exclusively on the male body and in a sense still does so, there is one area where things have gone differently and that is contraception.
Culturally considered an exclusively female issue, since the late 1950s science has studied and approved hormonal contraceptive methods only for women, so the side effects of hormonal dosages are considered part of the trade-off to avoid pregnancy, while in men, such effects – combined with the issue of decreased libido – have always prevented finding a solution.
Now, a new study from Cornell University in Ithaca, New York State, has conducted research on mice managing to reversibly block sperm production without causing hormonal changes or side effects.
THE BIOLOGICAL MECHANISM OF THE STUDY
The study, published in the scientific journal Proceedings of the National Academy of Sciences, was conducted by a group of scientists from Cornell University in Ithaca and demonstrated the possibility of temporarily interrupting sperm production in mice without compromising surrounding tissues and without affecting the hormonal system.
The target of the research was a precise stage of spermatogenesis, the process that leads to the formation of sperm and which includes three main phases: mitotic, meiotic, and spermiogenesis.
The researchers identified meiosis as the most vulnerable phase to intervene in, that is, the moment when germ cells reduce their chromosomal set to become mature sperm. By intervening at this stage, the production of sex cells can be suspended without acting directly on testosterone or the entire endocrine system.
Specifically, the compound used, JQ1, acts by interfering with a natural checkpoint of meiosis, blocking the progression of cell division and preventing sperm formation.
THE MOLECULE JQ1 AND THE INTERRUPTION OF SPERMATOGENESIS
JQ1, explain the researchers, is a small molecule originally developed as a research tool in oncology and inflammatory fields. In tests conducted on mice, the treatment eliminated cells in the first phase of meiotic division and blocked the genetic activation necessary for the subsequent stages of sperm development.
In subjects treated for three weeks, sperm production was completely halted, with alterations also in chromosome behavior during meiosis. The block occurred without affecting testosterone production, distinguishing this approach from many traditional hormonal strategies.
REVERSIBILITY AND RESTORATION OF FERTILITY
One of the central elements of the study concerns the reversibility of the effect. After stopping the treatment, mice recovered normal meiotic activity within about six weeks, returning to produce sperm at physiological levels.
Subsequently, the animals were able to reproduce, generating healthy and fertile offspring, who were also able to reproduce themselves. According to the researchers, moreover, the process did not compromise germ stem cells, allowing complete restoration of reproductive function.
WHERE MALE CONTRACEPTION STANDS
The research fits into a broader context where male contraceptive options remain limited to condoms, vasectomy, and some experimental techniques, such as thermal devices or interventions on the vas deferens.
Historically, research on male hormonal contraceptives has experienced slowdowns and interruptions compared to female research, mainly due to issues related to the acceptability of side effects and cultural and social factors. In this scenario, non-hormonal approaches like the one based on JQ1 or other experimental molecules are considered attempts to overcome the limitations that have so far characterized the development of male alternatives.
MOLECULAR MECHANISMS AND LIMITS OF THE MOLECULE
From a biological point of view, JQ1 acts by inhibiting BET family proteins, including BRDT, involved in activating genes necessary for meiosis and spermatogenesis. This causes an alteration of the chromatin of germ cells and blocks sperm production at the spermatocyte and spermatid levels.
However, BET proteins are not limited to testicular tissue alone and the molecule is not perfectly selective. For this reason, some analyses highlight the possibility of “off-target” effects, that is on other biological systems, given the role of BET proteins in global gene regulation. Furthermore, as mentioned, JQ1 has already been studied in other fields, such as oncology and inflammatory diseases, precisely because of its ability to interfere with gene expression regulation.
EXPERIMENTAL CLARIFICATIONS AND FUTURE DEVELOPMENTS
Available studies, moreover, concern exclusively animal models and there is still no evidence in humans regarding the safety and efficacy of the method. The reversibility observed in mice was monitored over relatively short periods, leaving open questions about the long term.
For this reason, JQ1 is not currently usable in clinical settings, also due to possible neurological side effects that emerged during research phases. The study is therefore considered primarily a proof of concept for exploring new contraceptive strategies.
HYPOTHESES OF USE AND PERSPECTIVES
Among future hypotheses, the researchers indicate the possibility of developing a male contraceptive administered via quarterly injection or transdermal patch, aiming to make the treatment simpler and not linked to daily administration. The declared intent is to expand the options available for male contraception and reduce the imbalance in reproductive responsibility, which today still predominantly falls on women.
