Male Contraceptive Research Articles

Reversible Modulation of Motile Cilia by a Benzo[e][1,2,4]triazinone: A Potential Non-Hormonal Approach to Male Contraception

Motile cilia play essential roles in various physiological processes including fluid flow generation and sperm motility. In this study, we identified 1,3-diphenyl-6-(4-phenylpiperazin-1-yl)benzo[e][1,2,4]triazin-7(1H)-one as a potent and reversible modulator of ciliary function using the Xenopus laevis model. This benzotriazinone derivative inhibits ciliary-driven fluid flow by inducing cilia detachment without causing toxicity in developing embryos. Unlike traditional deciliation agents that rely on calcium signaling, this compound induces cilia loss through a shear stress-driven mechanism at the transition zone, without disrupting tissue morphology or the apical actin network. Importantly, it also induces flagellar loss and impairs sperm motility at picomolar concentrations. Our findings highlight the potential of this 6-(4-phenylpiperazin-1-yl)-substituted benzotriazinone as a non-hormonal male contraceptive and underscore a novel mechanism of cilia modulation that may have broader implications for the treatment of cilia-related disorders.

Utilization of Male Contraceptives among Males in Bungoma County, Kenya

Purpose: Kenya has several policies to promote male participation in family planning, but data on male contraceptive use by male respondents is scanty. Available reports indicate that utilization of male contraceptives in Bungoma County to be less than 1%. This has been linked to high maternal deaths in Bungoma County. Limited male contraceptive choices has been cited as a barrier to utilization of current male contraceptives which calls for more research on male respondents to inform utilization, barriers, development and rollout of new male contraceptives. The aim of the study is to determine utilization of male Contraceptives among males in Bungoma County in Kenya. Methodology: A Cross-sectional Analytical study conducted among 395 males aged 20-69 years in Bungoma County in Kenya. Sample size was determined by Fisher et al. formula and multistage sampling technique was employed. Descriptive and inferential analyses were employed with p-value < 0.05 being considered significant. Findings: 80.9% of males are using aform of contraceptive with condom being the most used contraceptive (89.3%). Commodity related issues (X2 =40.570, p < 0.001), service delivery point (X2 = 82.252, p < 0.001), staff gender preference (X2 = 10.013, p = 0.018 were found to be statistically significant barriers to utilization. There was a significant association (X2 = 59.286, p < 0.001) between level of knowledge and utilization. 99% of the males are not aware of any other contraceptive other than condom vasectomy and withdrawal. If a new contraceptive was developed, the majority would prefer a pill when required. Unique Contribution to Theory, Practice and Policy: This study established a higher utilization of male contraceptives and influencers of utilization than earlier documented. Lack of knowledge by healthcare providers on new contraceptives calls for continuous medical education on the status of contraceptive development. These findings will inform the policy makers on the areas to focus on by leveraging on the existing opportunities to improve utilization of the current and any other contraceptive that is to be developed. It provides an opportunity for more research on male respondents.

Fertility Desires among Married Men in Rural Areas of Tanzania: Implications for Family Welfare and Sustainable Development

High fertility rates remain a major obstacle to family welfare, public health, and socioeconomic growth in Tanzania, especially in rural areas yet married men in these areas strongly desire large families. While understanding its drivers is essential for designing strategies to intervene in the situation research on specific drivers in rural areas is limited. This study aimed to assess the fertility desires among married men in rural areas of Tanzania and its implications for family welfare and sustainable development, specifically the study examines the prevalence of fertility desires among married men, analyzes its implications on family welfare and sustainable development, and examines the drivers for higher fertility rate in rural Tanzania. The study used the 2022 Tanzania Demographic and Health Survey (TDHS) data. A total of 3961 cases were analyzed to obtain the answer for this study. Both descriptive and inferential statistical data analyses were used in making the data analysis. The findings indicated that the fertility rate among married men in rural Tanzania is higher relative to their urban counterparts. Such a high rate implies, among others, that the family's economic welfare will be distorted, and parental care will be limited resulting in moral decay; increased maternal and child health problems, and pressure and depletion of resources will be increased. Men's desire for children is shaped by several factors, including age, education, knowledge of contraception, ideal number of children, number of living children, marital status, frequency of newspaper reading, and wealth index. Given the observed scenario, the study recommends that the government and non-government sectors should establish comprehensive efforts to promote family planning and reproductive health for better utilization of the available resources, encourage couple-based counselling at health facilities, promotion of male contraceptive methods such as condoms and vasectomy

Development of a transdermal gel for reversible male contraception.

Development of a transdermal gel for reversible male contraception.

Web traffic and Google Trends data show increased interest in novel male contraception following the Supreme Court's Dobbs v. Jackson ruling.

Web traffic and Google Trends data show increased interest in novel male contraception following the Supreme Court's Dobbs v. Jackson ruling.

Human efferent ductules and epididymis display unique cell lineages with motile and primary cilia.

Previous research has illustrated the role of cilia as mechanical and sensory antennae in various organs within the mammalian male reproductive system across different developmental stages. Despite their significance in both organ development and homeostasis, primary cilia in the human male reproductive excurrent duct have been overlooked due to limited access to human specimens. This study aimed to characterize the unique cellular composition of human efferent and epididymal ducts, with a focus on their association with primary cilia. Human efferent ductules/epididymides from five donors aged 32-47 years, were obtained through our local organ transplant program. Cell lineage specificity and primary cilia features were examined by immunofluorescent staining and confocal microscopy in the efferent ductules and the distinct segments of the epididymis. The epithelium of the human efferent duct exhibited estrogen receptor-positive cells with primary cilia, FoxJ1-positive multiciliated cells with numerous motile cilia, and non-ciliated intraepithelial immune cells. Notably, intraluminal macrophages, identified by CD163/CD68 positivity, were observed to engage in sperm phagocytosis. In all three segments of the human epididymis, primary cilia were found on the surface of principal and basal cells. Our research indicates that the human efferent ductules create a distinct environment, characterized by the presence of two types of ciliated cells that are in contact with immune cells. The discovery of sensory primary cilia exposed on the surface of reabsorptive cells in the efferent ductules, as well as on basal and principal cells in the epididymis, lays the foundation for complementary functional studies. This research uncovers novel characteristics exclusive to human efferent ductules and epididymides, providing a basis for exploring innovative approaches to male contraception and infertility treatment.

In Silico Discovery of Potential Inhibitors Targeting the MEIG1-PACRG Complex for Male Contraceptive Development.

The interaction between meiosis-expressed gene 1 (MEIG1) and Parkin co-regulated gene (PACRG) is a critical determinant of spermiogenesis, the process by which round spermatids mature into functional spermatozoa. Disruption of the MEIG1-PACRG complex can impair sperm development, highlighting its potential as a therapeutic target for addressing male infertility or for the development of non-hormonal contraceptive methods. This study used virtual screening, molecular docking, and molecular dynamics (MD) simulations to identify small molecule inhibitors targeting the MEIG1-PACRG interface. MD simulations provided representative protein conformations, which were used to virtually screen a library of 821 438 compounds, resulting in 48 high-ranking candidates for each protein. PACRG emerged as a favorable target due to its flexible binding pockets and better docking scores compared to MEIG1. Key binding residues with compounds included W50, Y68, N70, and E74 on MEIG1, and K93, W96, E101, and H137 on PACRG. MD simulations revealed that compound stability in MEIG1 complexes is primarily maintained by hydrogen bonding with E74 and π-π stacking interactions with W50 and Y68. In PACRG complexes, compound stabilization is facilitated by hydrogen bonding with E101 and π-π interactions involving W96 and H137. These findings highlight distinct molecular determinants of ligand binding for each protein. Our work provides mechanistic insights and identifies promising compounds for further experimental validation, establishing a foundation for developing MEIG1-PACRG interaction inhibitors as male contraceptives.

Identification of TSSK1 and TSSK2 as Novel Targets for Male Contraception.

The testis-specific serine kinases (TSSKs) are post-meiotically expressed in testicular germ cells. Their testis-specific expression, together with their putative role in phosphorylation pathways, suggests that TSSKs have relevant roles in spermiogenesis, sperm function, or both. Independent Tssk3 and Tssk6 knockout mice, as well as the double Tssk1/Tssk2 KO males, are sterile. However, the double KO results are silent regarding the individual roles of TSSK1 and TSSK2. The aim of this study was to develop independent mutant mouse models of Tssk1 and Tssk2, using CRISPR/Cas9, to evaluate their independent roles in reproduction. Male heterozygous pups were used to establish one Tssk1 and two independent Tssk2 mutant lines. Natural mating mutant Tssk1 and Tssk2 homozygous males but not females were found to be sterile. Additionally, homozygous males have lower sperm numbers and decreased motility, and were infertile in vitro. Anti-TSSK2 antibodies were validated against Tssk2 mutants and used in Western blot and immunofluorescence experiments. TSSK2 is localized to the sperm head; importantly, it is present in the testes and sperm from Tssk1 mutant mice, confirming individual mutation. Our results indicate that both TSSK1 and TSSK2 are individually essential for male reproduction and support both kinases as suitable nonhormonal male contraceptive targets.

Prevalence of male and female permanent contraception and long-acting reversible contraceptives among commercially insured US population, 2010-2022.

Prevalence of male and female permanent contraception and long-acting reversible contraceptives among commercially insured US population, 2010-2022.

Factors associated with uptake of dual contraceptives among women receiving family planning methods in Harare, Zimbabwe: a cross-sectional study

Dual contraception is crucial for preventing both unintended pregnancies and HIV/STIs, especially for women living with HIV. However, the impact of HIV status on dual contraception uptake is not well understood. This study assessed the association between HIV status and dual contraception use among women at Spilhaus Clinic. A cross-sectional pilot study recruited 80 women (18–49 years) seeking family planning services between January and April 2024. The mean age was 33.5 years, and 66.3% were married. Dual contraception prevalence was 31.2%, with male condoms and pills (54.8%) being the most common method. Women with HIV (83%) were significantly more likely to use dual contraception than HIV-negative women (27%; p = .01). Income level also influenced uptake (p = .004). Women with HIV had 3.09 times higher prevalence of use (p < .0001). Findings emphasize the need for targeted education and counseling on dual contraception, especially for high-risk groups.

Structural basis of the multiple ligand binding mechanisms of the P2X1 receptor.

As important modulators of human purinergic signaling, P2X1 receptors form homotrimers to transport calcium, regulating multiple physiological processes, and are long regarded as promising therapeutic targets for male contraception and inflammation. However, the development of drugs that target the P2X1 receptor, such as the antagonist NF449, is greatly hindered by the unclear molecular mechanism of ligand binding modes and receptor activation. Here, we report the structures of the P2X1 receptor in complex with the endogenous agonist ATP or the competitive antagonist NF449. The P2X1 receptor displays distinct conformational features when bound to different types of compounds. Despite coupling to the agonist ATP, the receptor adopts a desensitized conformation that arrests the ions in the transmembrane (TM) domain, aligning with the nature of the high desensitization rates of the P2X1 receptor within the P2X family. Interestingly, the antagonist NF449 not only occupies the orthosteric pocket of ATP but also interacts with the dorsal fin, left flipper, and head domains, suggesting a unique binding mode to perform both orthosteric and allosteric mechanisms of NF449 inhibition. Intriguingly, a novel lipid binding site adjacent to the TM helices and lower body of P2X1, which is critical for receptor activation, is identified. Further functional assay results and structural alignments reveal the high conservation of this lipid binding site in P2X receptors, indicating important modulatory roles upon lipid binding. Taken together, these findings greatly increase our understanding of the ligand binding modes and multiple modulatory mechanisms of the P2X1 receptor and shed light on the further development of P2X1-selective antagonists.Keywords: Structural biology; Ligand binding mode; Ion channel; Purinergic P2X1 receptor.

Motivations to use a novel hormonal male contraceptive: Perspectives from male contraceptive clinical trial participants.

Most existing studies on men's willingness to use novel hormonal male contraceptives (HMCs) rely on survey data and focus on the hypothetical use of HMCs. The aim of this in-depth, qualitative study was to elicit the perspectives of HMC clinical trial participants - men who have actually used an HMC - to describe their motivations for using HMCs. In 2017-18 we conducted 30 in-depth, semi-structured interviews with a sample of men who participated in early-stage HMC clinical trials in Los Angeles or Seattle to explore their experiences with and motivations for trialing a HMC. Using thematic analysis, we analyzed deidentified transcripts using deductive and inductive codes, summarizing key themes using a socioecological framework. Participants averaged 35 years old (range: 22-52) and were ethnically and sociodemographically diverse. Men's motivations for using an HMC centered on societal-level factors (i.e., concerns regarding 'overpopulation' and responsible childbearing), partnership factors (concerns regarding entrapment; desire to share in contraceptive responsibility), and individual-level factors (i.e., contraceptive options that maximized pleasure and intimacy; beliefs in men's contraceptive and bodily autonomy). This study provides the first U.S.-based, in-depth qualitative insights from men who have used HMCs. Men's motivations for participating in HMC clinical trials and wanting to use novel male contraceptives are both numerous and multi-faceted, supporting prevailing survey data on men's willingness to use them once on the market. These data offer insights on how male contraceptives could be marketed to the general public. Men's motivations vary with respect to participation in hormonal male clinical trials and desire to use HMCs when they become available. All of these motivations - from the broader, societal level, to the individual and partnership level - are critical to assessing the demand for and subsequent marketing of HMCs.

Proton-secreting cells modulate mucosal immune surveillance in the male reproductive tract.

Proton-secreting cells in various organs, such as the kidney and epididymis, regulate pH balance, maintaining cellular homeostasis, and supporting key physiological processes. More recently, these specialized cells have emerged as key contributors to mucosal immunity, orchestrating immune activation. Epididymitis is an inflammatory condition that significantly impacts male fertility, often due to a lack of diagnosis and treatment. This study explores the involvement of region-specific epididymal proton-secreting clear cells (CCs) in the immune response by interacting with the immune system during LPS-induced mouse epididymitis. We found that in response to LPS, CCs rapidly shifted to a proinflammatory phenotype, marked by the upregulation of cytokines and chemokines, alongside the downregulation of genes involved in sperm maturation. Morphological changes in CCs, including increased apical blebs and altered shape across different epididymal segments, suggest their active role in immune responses. Moreover, mononuclear phagocytes (MPs) reduced their luminal-reaching projections in the proximal epididymis after the LPS challenge. This bacteria antigen triggered the migration of dendritic cells and neutrophil infiltration in the distal epididymis. These immune landscape alterations contributed to epithelial damage and impaired sperm maturation, as evidenced by decreased sperm motility following LPS injection. Our findings indicate that proton-secreting cells are immune gatekeepers in the epididymis, initiating immune responses and disrupting sperm maturation. This research enhances the understanding of epithelial immunoregulation and will help to develop novel diagnostic and therapeutic strategies for epididymitis and male infertility. Furthermore, insights into CC-mediated immune responses could inform the development of new approaches for male contraception.

Pre-clinical Outcomes of Plant-based Male Oral Contraceptive: A Critica Review

Abstract: This current review provides a thorough examination of the potential of plant-based chemicals as effective male contraceptive treatments by synthesizing results from several preclinical investigations. The established literature highlights the urgent requirement for male contraceptive strategies that are safe, effective, and reversible, considering the drawbacks and difficulties of current options. The need for male contraceptive research and the inherent drawbacks of available solutions are also covered in this review. It clarifies the possible benefits of plant-based contraceptives by emphasizing their natural source, expected safety profile, and low side effect rate. In this review, 49 plants evaluated for male oral contraceptive action are discussed. PubMed, Cochrane library, Embase, ScienceDirect, and Google Scholar databases are used for the literature search. This review explores the complex pathways, including hormone regulation, spermatogenesis suppression, sperm motility interference, and sperm maturation disruption, by which plant-based chemicals may have contraceptive effects. Pre-clinical investigations have examined a wide range of plant-derived substances, including flavonoids, anthraquinones, glycosides, alkaloids, phenolics, diterpenes, triterpenes, tannins, saponins, steroids, and phytosterols, among other phytochemical families. Every phytochemical is thoroughly examined, including its botanical origins, phytoconstituents, native name, and unique effects on male fertility. Results from research conducted on animals are methodically summarised in this study, including information on the effectiveness, dose, delivery methods, and reversibility of contraceptive effects. Furthermore, the discussion includes findings from in vitro research, emphasizing the possible influence on sperm parameters (sperm production, deformation, count, viability, and motility), reproductive hormones (testosterone level), thickness and diameter of seminiferous tubules (ST) as well as spermatocytes and secondary spermatocytes, Sertoli cells (SCs), and Leydig cell (LCs). According to the assessment, male contraceptives made of plants have a lot of potential as a future weapon in the arsenal of contraceptives. Preclinical research has shown the safety, effectiveness, and reversibility of several plant-derived drugs, which offers a solid basis for more investigation and advancement. However, there are still a lot of obstacles to overcome, like standardizing plant extracts, guaranteeing uniform effectiveness, and carrying out thorough safety evaluations. This review emphasizes the significance of undertaking well-designed clinical studies to validate pre-clinical findings, creating standardized formulations for consistent outcomes, and resolving regulatory issues as well as ethical considerations for human use to progress this subject.

Male Hormonal Contraception-Current Stage of Knowledge.

Male hormonal contraception has been the focus of extensive research efforts aimed at identifying effective and reversible methods for male fertility control. This review summarizes the current state of knowledge, key achievements, and future directions in the development of male hormonal contraception. A review was conducted using the PubMed, Embase, and Scopus databases. The search strategy included terms such as "male hormonal contraception", "Nestorone", "7α,11β-Dimethyl-19-nortestosterone 17β-undecanoate (DMAU)" and "11β-methyl-19-nortestosterone 17β-dodecylcarbonate (11β-MNTDC)". A total of 107 references were analyzed to synthesize the most relevant findings regarding the hormonal contraceptive agents under investigation. The review outlines historical and recent advancements in male hormonal contraception, highlighting compounds that have demonstrated limitations in effectiveness, side effects, or inconvenient administration. Notable candidates under study include 7α-methyl-19-nortestosterone (MENT), DMAU, 11β-MNTDC, and the combination of segesterone acetate with testosterone in gel form. These agents show promise due to their ability to suppress follicle-stimulating hormone (FSH) and luteinizing hormone (LH), leading to effective spermatogenesis inhibition with minimal side effects. Additionally, the phenomenon of spermatogenic rebound is considered. Among the investigated agents, oral DMAU, 11β-MNTDC, and the Nestorone-testosterone gel appear to be the most promising candidates for male hormonal contraception due to their high efficacy, user-friendly administration, and favorable safety profiles. However, further large-scale clinical trials are necessary to confirm their long-term effects on human health and fertility, ensuring their viability as future contraceptive options.

Defensive Responses to Masculinity Threat: The Role of Precarious Manhood in Reactions to the Male Contraceptive Pill

ABSTRACT This study examines how men evaluate a potentially masculinity-threatening message about the availability of a male birth control pill, framed as being released in the near versus distant future. Drawing on research on health-related defense mechanisms and precarious manhood, we hypothesized that men with higher levels of precarious manhood beliefs would react more defensively to the message – exhibiting greater message derogation, avoidance, lower perceived efficacy, and heightened concerns about side effects – especially when the pill was framed as being released soon. We further explored whether these defensive evaluations mediated the relationship between precarious manhood and intentions, moderated by temporal framing. To test these hypotheses, a sample of 398 men (M = 42.90, SD = 12.38) read an article describing a male birth control pill framed as either being released in the near or distant future. Participants then reported their perceptions of the article and the pill, their behavioral intentions, and their precarious manhood beliefs. Regression analyses showed that precarious manhood significantly predicted greater avoidance and higher perceptions of side effects. Moreover, higher perceived side effects mediated the association between precarious manhood and intentions to purchase the pill when it was framed as being released in the near future, but not when framed as being released in the distant future. These findings highlight the role of defensiveness in shaping how men with strong precarious manhood beliefs respond to masculinity-threatening health messages. Careful consideration of message framing, particularly in media presentations of male contraceptives, is crucial to mitigate defensive reactions that could hinder desired behavioral outcomes.

Pelvic vasectomy and its protective effects on rat testis function

BackgroundVasectomy is a commonly used male contraceptive method, but the choice of surgical technique can influence long-term reproductive health outcomes. Previous studies suggest that different vasectomy techniques may lead to varying degrees of tissue damage, oxidative stress, and endocrine dysfunction. However, there is limited research on how these techniques affect overall reproductive system function. Therefore, this study aims to evaluate and compare the effects of two vasectomy techniques on reproductive system parameters in rats.MethodsTwenty-four specific pathogen-free male Sprague–Dawley rats weighing 250–300 g were randomly divided into four groups: sham operation group, negative control group, traditional vasectomy group, and modified vasectomy group, with six rats in each group. Each group underwent specific vasectomy procedures, followed by a three-month recovery period. Experimental methods included hematoxylin and eosin staining, immunohistochemistry in the epididymis of rats, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling for apoptosis detection, enzyme-linked immunosorbent assay for measuring serum hormone and oxidative stress markers, as well as tests for sexual behavior and anxiety-like behavior.ResultsThe modified vasectomy group exhibited improved epididymis morphology compared to the traditional vasectomy group. Immunohistochemistry demonstrated reduced levels of apoptosis in the modified vasectomy group, which was further corroborated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining, indicating lower cell death. Hormone analysis revealed stable levels in the modified vasectomy group, and oxidative stress markers indicated reduced stress responses. Behavioral test assessing sexual activity and anxiety level was consistent with these findings.ConclusionModified vasectomy techniques provide superior protection of reproductive system functionality in rats compared to traditional methods. These techniques reduce tissue damage, cell apoptosis, and oxidative stress while maintaining endocrine function, offering promising implications for clinical applications.

The Molecular Mechanisms of Natural Medicinal Active Ingredients Interfering with Male Fertility.

The challenges posed by excessive global population growth remain significant. Hormonal female contraceptive pills, which have been approved for over 60 years, serve as an important means of contraception; however, many women experience adverse effects after taking these pills, including abnormalities in blood clotting, dizziness, headaches, and vomiting. In this context, male contraceptives have emerged as a prominent area of research. Unfortunately, most male contraceptives are still in the experimental or clinical research stages. Therefore, screening for active ingredients that can specifically inhibit sperm function from natural drug active ingredient libraries holds substantial clinical and practical significance. In this manuscript, we review the inhibitory effects of various natural drug active monomers on sperm function and their underlying molecular mechanisms, aiming to provide theoretical insights for the future development of novel male contraceptives.

Targeting cyclin-dependent kinase 2 (CDK2) interactions with cyclins and Speedy 1 (Spy1) for cancer and male contraception.

The review discusses progress in discovering cyclin-dependent kinase 2 (CDK2) inhibitors for cancer treatment and their potential for male contraception. It summarizes first-, second-, and third-generation CDK inhibitors and selective CDK2 inhibitors currently in clinical trials for cancer. Novel strategies to discover allosteric inhibitors, covalent inhibitors, and degraders are also discussed.

Pharmacognostic, GC-MS, and In Silico Molecular Docking Studies of Phytoconstituents from Urtica dioica and Zanthoxylum armatum for Male Antifertility Potential.

Research on non-hormonal alternatives to traditional methods of male contraception has been prompted by the growing world population as well as the need for effective and reversible treatments. This study aimed to examine the possible antifertility potential of two medicinal herbs, i.e., Urtica dioica and Zanthoxylum armatum, that have been utilized for centuries in different cultures. A thorough pharmacognostical analysis was carried out to identify the ingre-dients of these plants. The phytoconstituents from Urtica dioica aqueous 96% methanolic leaf extract and Zanthoxylum armatum fruit essential oil were subjected to in silico molec-ular docking screening. The phytoconstituents were profiled using GC-MS analysis. To in-vestigate how these phytoconstituents interact with important proteins involved in male fer-tility and identify potential candidates for the development of a plant-based oral contracep-tive for men, further in silico molecular docking (receptor protein ID of 7FIH (3.20 Å), 7BPR (1.95 Å), and 2Q7J (1.90 Å) ) experiments were carried out. The GC-MS analysis revealed a wide variety of bioactive chemicals. Promising interactions between the discovered phytoconstituents and specific protein targets were found by the in silico molecular docking investigation, indicating the possibility of antifertil-ity effects. The results of this study demonstrate the medicinal use of these plants and provide the basis for the development of novel male contraceptive medicines and their fur-ther experimental validation.