Novel Genes of the Male Reproductive System: Potential Roles in Male Reproduction and as Non-hormonal Male Contraceptive Targets.

The development of novel non-hormonal male contraceptives represents a pivotal frontier in reproductive health, driven by the need for safe, effective, and reversible contraceptive methods. This comprehensive review explores the genetic underpinnings of male fertility, emphasizing the crucial roles of specific genes and structural variants (SVs) identified through advanced sequencing technologies such as long-read sequencing (LRS). LRS has revolutionized the detection of structural variants and complex genomic regions, offering unprecedented precision and resolution over traditional next-generation sequencing (NGS). Key genetic targets, including those implicated in spermatogenesis and sperm motility, are highlighted, showcasing their potential as non-hormonal contraceptive targets. The review delves into the systematic identification and validation of male reproductive tract-specific genes, utilizing advanced transcriptomics and genomics studies with validation using novel knockout mouse models. We discuss the innovative application of small molecule inhibitors, developed through platforms like DNA-encoded chemistry technology (DEC-Tec), which have shown significant promise in preclinical models. Notable examples include inhibitors targeting serine/threonine kinase 33 (STK33), soluble adenylyl cyclase (sAC), cyclin-dependent kinase 2 (CDK2), and bromodomain testis associated (BRDT), each demonstrating nanomolar affinity and potential for reversible and specific inhibition of male fertility. This review also honors the contributions of Dr. David L. Garbers whose foundational work has paved the way for these advancements. The integration of genomic, proteomic, and chemical biology approaches, supported by interdisciplinary collaboration, is poised to transform male contraceptive development. Future perspectives emphasize the need for continued innovation and rigorous testing to bring these novel contraceptives from the laboratory to clinical application, promising a new era of male reproductive health management.

The male birth control pill - A new approach to family planning and population control.

With the increase in the world's population, contraception is crucial in population control strategies. Majority of contraceptives produced today are targeted at women; many of whom experience side effects, leading to the discontinuation of these contraceptives after a year of use. As the use of condoms and vasectomies has been subjected to scrutiny, it is necessary for the development of male birth control (BC). Attempts to achieve this include hormonal and non-hormonal contraception. Hormonal contraception prevents the production of the sperm in the testes; but this mode of BC has been found to be ineffective while also causing behavioural changes in men. In contrast, non-hormonal male contraception focuses on rendering the sperm immotile to prevent fertilization post-copulation. Soluble adenylate cyclase is an area of research that has shown promise in this field. Furthermore, two inhibitors, TDI-10299 and TDI-11861, have been developed and tested, with the latter, showing greater potency and longer activity, in mice models. Overall, by developing non-hormonal male contraceptives, men will have more control over their reproductive health. Nonetheless, before such contraceptives can be made widely available, it is important that further research takes place to ensure the safety and effectiveness of these methods.

In silico Docking Analysis for Blocking JUNO-IZUMO1 Interaction Identifies Two Small Molecules that Block in vitro Fertilization.

Combined hormone drugs are the basis for orally administered contraception. However, they are associated with severe side effects that are even more impactful for women in developing countries, where resources are limited. The risk of side effects may be reduced by non-hormonal small molecules which specifically target proteins involved in fertilization. In this study, we present a virtual docking experiment directed to discover molecules that target the crucial fertilization interactions of JUNO (oocyte) and IZUMO1 (sperm). We docked 913,000 molecules to two crystal structures of JUNO and ranked them on the basis of energy-related criteria. Of the 32 tested candidates, two molecules (i.e., Z786028994 and Z1290281203) demonstrated fertilization inhibitory effect in both an in vitro fertilization (IVF) assay in mice and an in vitro penetration of human sperm into hamster oocytes. Despite this clear effect on fertilization, these two molecules did not show JUNO-IZUMO1 interaction blocking activity as assessed by AVidity-based EXtracellular Interaction Screening (AVEXIS). Therefore, further research is required to determine the mechanism of action of these two fertilization inhibitors.

Norwegian women's experiences and opinions on contraceptive counselling: A systematic textcondensation study.

INTRODUCTION: Contraception plays a pivotal role in most women's lives, from teenage years to the menopause. Contraception and sexual wellbeing are closely related. Ideally, women should be able to access contraception and discuss issues concerning their sexual life during a contraceptive counselling session. Previously, only doctors conducted contraceptive consultations. Increasingly, other healthcare workers are providing contraceptive care. The aim of this study is to explore women's experiences and opinions related to contraceptive counselling. METHODS: An electronic questionnaire was distributed in 2017-2018. The texts of 308 women's written responses to open-ended questions were analyzed using systematic text-condensation. RESULTS: The analysis resulted in four themes: 1) Women-centered care, 2) Side-effects of hormonal contraceptives, 3) Non-hormonal methods and male involvement, and 4) Counsellors' professional background. Women wished for a consultation that would lead to the best choice of contraception for them, taking into account their medical history, personal preference and living circumstances. Side-effects of hormonal products were under-communicated, as were non-hormonal methods. Respondents had contradicting opinions about midwives as contraceptive counsellors and were unfamiliar with them in this role. CONCLUSIONS: The quality of contraceptive counselling in Norway needs to be improved. Women require individualized follow-up, sufficient information and a choice of methods to find the most suitable alternative for them. A good relationship with a health provider they trust could improve contraceptive consultation. Midwives' knowledge and competence in this area need to be made more widely known.