This blog series highlights pertinent publications that were featured in MCI's monthly newsletter editions in the third quarter of 2023. The purpose of this blog is to report interesting or relevant work from MCI Fellows, Grantees, staff members, and other community authors in the field of male contraception.
This publication from former MCI Fellow Oleksander “Sasha” Kirsanov outlines the role of retinoic acid in spermatogenesis, revealing a model of meiotic initiation wherein retinoic acid plays a role in a commitment to meiosis, is dispensable for subsequent steps of meiosis, and then plays an important role in spermiogenesis. The proposed role of retinoic acid (RA) as the 'meiosis-inducing substance' in mammals has primarily been based on studies in the fetal ovary, where germ cell differentiation and meiotic initiation occur simultaneously. However, in the postnatal testis, these events are separated by more than a week. Recent research has uncovered that while RA is necessary for spermatogonial differentiation, it is not essential for the subsequent initiation, progression, and completion of meiosis. In the absence of RA, the meiotic transcriptome program in both differentiating spermatogonia and spermatocytes entering meiosis remains largely unaffected. These findings challenge the traditional notion of RA's indispensable role in male meiotic initiation, highlighting an RA-independent model for this process.
Reproductive health faces significant challenges, including high HIV and STI rates and an unmet need for modern contraception leading to unintended pregnancies. This review co-authored by current MCI grantee Deborah Anderson outlines the history of MPT products, current status of MPTs and their prospects, and design considerations for future cMPTs. Multipurpose prevention technology (MPT) emerged as a response to failed microbicide candidates in preventing HIV transmission. MPTs aim to simultaneously address unintended pregnancy, HIV, and other STIs. Contraceptive MPT products (cMPTs) seek to provide contraception and protection against major STIs like HIV, herpes, gonorrhea, syphilis, trichomoniasis, and chlamydia. This evolving field encompasses various categories with different mechanisms, such as pH modifiers, polyions, microbicidal peptides, monoclonal antibodies, and other peptides targeting reproductive and infectious processes. Extensive preclinical research focuses on safety and efficacy. Effective candidates are combined to enhance effectiveness, minimize side effects, and prevent drug resistance. Attention is also given to acceptability and new delivery systems. With sufficient resources, cMPTs hold great promise for the future by offering effective, acceptable, and affordable products for reproductive health challenges.
The proximal region of the epididymis is critical for sperm transport, maturation, and fertility. . It is divided into segments with differential gene expression, including many target genes for male contraception. This publication provides an RNA-seq resource of regionally-specific genes in the caput epididymis. The study used precise microdissection techniques to isolate the initial segment (IS) and proximal caput (P-caput) of the epididymis in mice. RNA sequencing revealed distinct transcriptome changes in these regions, with 1,961 genes abundantly expressed in the IS and 1,739 genes prominently expressed in the P-caput. Many differentially expressed genes (DEGs) were unique to the epididymis, and region-specific genes were associated with crucial functions like transport, secretion, sperm motility, fertilization, and male fertility. This research provides valuable insights into segment-specific epididymal functions and identifies potential targets for male contraception and reproductive health.
This publication from former MCI Fellow Melanie Balbach shows that capacitation-induced changes lead to increased flux through both glycolysis and oxidative phosphorylation in mouse and human sperm. Sperm in mammals need ample energy to facilitate motility and capacitation, crucial for successful fertilization. Prior investigations into sperm metabolism focused on either ejaculated human sperm or dormant mouse sperm extracted from the cauda epididymis. This distinction in collection methods left questions regarding whether observed metabolic differences between mouse and human sperm were due to species variations or differences in sperm maturation states. This study compares metabolic alterations during capacitation between epididymal and ejaculated mouse sperm and draws comparisons to ejaculated human sperm. Through extracellular flux analysis and targeted metabolic profiling, the research reveals that capacitation-induced changes lead to increased metabolic flux in both glycolysis and oxidative phosphorylation in both mouse and human sperm. Ejaculation enhances the flexibility of using various carbon sources. While epididymal sperm rely on glucose, ejaculated mouse and human sperm gain the capacity to utilize non-glycolytic energy sources like pyruvate and citrate.
While hormonal contraceptives are effective, concerns about their safety and side effects deter many individuals. This review from the lab of MCI Grantee Rahima Benhabbour covers non-hormonal contraceptives in development and highlights many specific contraceptive targets and research programs. Non-hormonal contraceptive options include permanent sterilization, copper intrauterine devices (IUDs), barriers like spermicides and condoms, and traditional family planning methods. Long-acting, reversible contraceptives (LARCs) are highly effective, but only one, the copper IUD, is non-hormonal. With high rates of unintended pregnancies persisting, there's growing interest in developing new pregnancy prevention methods for both genders. Non-hormonal contraceptives can target various critical reproductive processes. This review focuses on identified non-hormonal contraceptive targets and the development of drug candidates to address these targets, offering the promise of safer and more accessible contraceptive choices for individuals looking to retain their fertility in the future.
This study assessed men's attitudes towards various male birth control (MBC) methods, including gels, pills, injections, implants, and vas occlusion, along with their willingness to use these methods. Among participants with recent female sexual partners, 72% expressed a high level of willingness to use at least one MBC method. However, preferences for specific methods varied, with pills being the most favored (62%) and vas occlusion the least (24%). Age and prior HIV testing were associated with MBC willingness, while concerns about side effects and cost were common barriers. This research highlights the need for further investigation into MBC attitudes across diverse populations to inform future contraceptive development.
Are there any interesting publications about non-hormonal, reversible male contraception that you'd like to see featured? Please reach out to us and share your thoughts!