Title : Navigating non-hormonal contraceptives - Targeting biochemical mechanisms of contraception in a preclinical ovine model
Abstract:
Introduction: Vaginally administered non-hormonal contraceptive (NHC) methods are currently being explored for a non-systemic approach to minimize side effects. Developing efficacious NHCs requires testing consistent with the target effect along the sperm’s path to fertilization using a large ovine preclinical model before product use in humans.
Methods: PubMed and NIH Reporter were searched using terms ("non-hormonal contraceptives," "sperm motility," and "reversible contraceptive") to identify current and developmental NHCs for analysis of potential contraceptive mechanisms. Non-English articles were excluded.
Results: NHC mechanisms can be divided into drugs impacting the lower (e.g. sperm viability/motility) or upper (e.g. capacitation/hyperactivation, acrosome reaction) reproductive tract. Lower tract mechanisms include preventing semen liquefaction by increasing viscosity, thickening cervical mucus, decreasing sperm motility (e.g. altering mitochondrial functioning or flagellar modifications, agglutination), and decreasing vaginal pH. Tests include protease activity assays for liquefaction, microscopic cervical mucus or sperm motility assessment, sperm Na-K ion transport, and pH testing.
Upper reproductive tract mechanisms target capacitation/hyperactivation, which can be tested with fluorescent-labeled Kemptide (KiMSA) to assess cAMP/PKA or by measuring reactive oxygen species through chemiluminescence detection in flow cytometry. Premature acrosomal reactions can be tested with microscopy, flow cytometry, or fluorescent lectins.
Conclusion: There is a need to ensure that preclinical models, including the large ovine model, provide comprehensive approaches to testing the numerous potential NHC mechanisms. This is a vital step to increase contraceptive option translation to clinical studies and future accessibility to new methods to avoid unplanned pregnancies.
Audience Take Away:
- The audience will gain a deeper understanding of how non-hormonal contraceptives function at various stages of sperm viability within the female reproductive tract.
- Participants will learn about the biomechanical principles and efficacy of testing non-hormonal contraceptives in sheep vaginal models.
- This knowledge will equip healthcare providers with information about diverse non-hormonal contraceptive options and their mechanisms of action. This will enable them to offer comprehensive counseling and empower patients to make informed decisions.
- This research will encourage researchers to utilize large animal models, such as sheep, to study the efficacy and potential impacts of hormonal and non-hormonal contraceptives in development.
- This research aims to enhance the accuracy of contraceptive design by providing insights into the various ways the efficacy of non-hormonal contraceptives can be tested apart from microscopic evaluation. This will lead to more precise preclinical testing and informed clinical recommendations.
