INHIBICIÓN SINÉRGICA DE LA FUNCIÓN ESPERMÁTICA HUMANA POR FUCOIDAN Y OUABAÍNA REVELA UNA POTENTE ESTRATEGIA ANTICONCEPTIVA NO HORMONAL

Resumen

El desarrollo de opciones anticonceptivas no hormonales seguras y eficaces es una prioridad global, especialmente considerando la irritación mucosal y las respuestas inflamatorias asociadas con espermicidas químicos como el Nonoxinol‑9 y el Lauril Sulfato de Sodio. Los compuestos bioactivos naturales han surgido como alternativas prometedoras debido a sus diversas propiedades biológicas y a perfiles de seguridad potencialmente superiores. Este estudio investigó los efectos in vitro de Fucoidan, un polisacárido sulfatado derivado de algas pardas, y Ouabaína, un glucósido cardiotónico que inhibe selectivamente la isoforma α4 de la Na⁺/K⁺‑ATPasa específica de los espermatozoides, sobre la motilidad y la vitalidad de espermatozoides humanos. Muestras de semen de voluntarios sanos fueron expuestas a solución salina (control negativo), Lauril Sulfato de Sodio (control positivo), Fucoidan, Ouabaína o a la combinación Fucoidan + Ouabaína, y evaluadas a los 0 y 15 minutos según las directrices de la OMS (2021). Todos los tratamientos redujeron la motilidad y la vitalidad en comparación con el control negativo. El Fucoidan produjo reducciones moderadas, mientras que la Ouabaína generó un efecto inhibitorio más pronunciado. La combinación resultó en el mayor descenso, reduciendo la motilidad progresiva y la vitalidad en aproximadamente un 28% en ambos tiempos, lo que indica una interacción sinérgica. Los análisis estadísticos (Kruskal–Wallis y Wilcoxon) confirmaron diferencias significativas entre los tratamientos (p < 0,05). 

Biografía del autor/a

Paula Gabriella Pedras Silva, Universidad Federal de Espírito Santo, Vitória, Brasil

Maestría en Biotecnología en Saludad 
Especialista en Salud de la Mujer
Licenciatura en Enfermería y Obstetricia

Milena de Oliveira Correa, Universidad Federal de Espírito Santo, Vitória, Brasil

Licenciada en Enfermería y Obstetricia por la Universidad Federal de Espírito Santo (UFES); candidata a doctora en Salud Pública (UFES); Máster en Salud Pública (UFES).

Hellyezer Vilela de Morais, Universidad Federal de Espírito Santo, Vitória, Brasil

Licenciada en Farmacia por la Universidad Federal de Espírito Santo (UFES); estudiante de Maestría en Biotecnología en Salud (UFES).

Matheus Correia Casotti, Universidad Federal de Espírito Santo, Vitória, Brasil
285 Licenciado en Ciencias Biológicas por el Centro de Genética Humana y Molecular (NGHM) del Departamento de Ciencias Biológicas de la Universidad Federal de Espírito Santo (UFES); Máster en Biotecnología (UFES). Doctorando/estudiante de doctorado en Biotecnología (RENORBIO/UFES).
Flávia de Paula, Universidad Federal de Espírito Santo, Vitória, Brasil;

Licenciado en Ciencias Biológicas por la Universidad Federal de Espírito Santo (UFES); Doctor en Ciencias/Genética por la Universidad de São Paulo (USP). Profesor, asesor e investigador del Programa de Posgrado en Biotecnología/UFES.

Iúri Drumond Louro, Universidad Federal de Espírito Santo, Vitória, Brasil

Posdoctorado en Bioquímica y Genética Molecular (UAB) y posdoctorado en Genética Molecular del Cáncer. Profesor Titular (UFES), supervisor de estudiantes de máster y doctorado en Biotecnología. Coordinador del Programa de Posgrado en Biotecnología de la UFES.

Breno Valentim Nogueira, Universidad Federal de Espírito Santo, Vitória, Brasil

Doctor en Ciencias Fisiológicas (UFES). Profesor Asociado IV del Departamento de Morfología de la UFES, con especialización en Morfología/Histología, Biología Celular, Bioingeniería Tisular, Biofísica y Fisiología. Coordinador del programa de doctorado de la Red de Biotecnología del Nordeste (RENORBIO) y supervisor de estudiantes de maestría y doctorado en Biotecnología (UFES).

Débora Dummer Meira, Universidad Federal de Espírito Santo, Vitória, Brasil

Posdoctorado en Biociencias (UERJ). Doctorado en Biociencias Nucleares con énfasis en Oncología Molecular (UERJ/INCA). Máster en Ciencias Farmacéuticas (UFRJ) y especialización en Bioquímica (UFES) y Docencia Superior (EMESCAM). Farmacéutico (UFES). Profesor e investigador del Programa de Posgrado en Biotecnología (PPGBIOTEC).

Referencias

ABE, K. et al. Molecular structure of the Na+,K+-ATPase α4β1 isoform in its ouabain-bound conformation. International Journal of Molecular Sciences, v. 25, n. 22, p. 12397, 2024. DOI: https://doi.org/10.3390/ijms252212397

AMATYA, B. et al. SNX19 interacts with caveolin-1 and flotillin-1 to regulate D1R endocytosis and signaling. Biomedicines, v. 13, n. 2, p. 481, 2025. DOI: https://doi.org/10.3390/biomedicines13020481

BARTON, B. et al. Serine protease inhibitor disrupts sperm motility leading to reduced fertility in female mice. Biology of Reproduction, v. 103, p. 400–410, 2020. DOI: https://doi.org/10.1093/biolre/ioaa049

BENJAMINI, Y.; YEKUTIELI, D. The control of the false discovery rate in multiple testing under dependency. The Annals of Statistics, v. 29, n. 4, p. 1165–1188, 2001. DOI: https://doi.org/10.1214/aos/1013699998

CHIANESE, R.; PIERANTONI, R. Mitochondrial reactive oxygen species (ROS) production alters sperm quality. Antioxidants, v. 10, n. 1, p. 92, 2021. DOI: https://doi.org/10.3390/antiox10010092

CHOLLET, L. et al. Fucoidans in nanomedicine. Marine Drugs, v. 14, n. 8, p. 145, 2016. DOI: https://doi.org/10.3390/md14080145

CONTRERAS, R. et al. Na+/K+-ATPase: More than an electrogenic pump. International Journal of Molecular Sciences, v. 25, n. 11, p. 6122, 2024. DOI: https://doi.org/10.3390/ijms25116122

HAINEAULT, C.; LECLERC, P.; GAGNON, C. Characterization of human sperm surface antigens involved in gamete interaction. Molecular Human Reproduction, v. 9, n. 5, p. 279–286, 2003. DOI: https://doi.org/10.1093/molehr/gag037

HASSAN, M. et al. Reversibility of the reproductive toxicity of gossypol in peripubertal bulls. Theriogenology, v. 61, n. 6, p. 1171–1179, 2004. DOI: https://doi.org/10.1016/j.theriogenology.2003.07.007

HATCHER, R. A. Contraceptive technology. 21. ed. Managing Contraception, LLC, 2018.

HE, Y. et al. Anti-hyperlipidemic effect of fucoidan fractions prepared from Iceland brown algae Ascophyllum nodosum in a hyperlipidemic mice model. Marine Drugs, v. 21, 2023. DOI: https://doi.org/10.3390/md21090468

HEREDERO-JIMÉNEZ, S. et al. Caveolin-1 regulates parathyroid hormone-related protein actions on PTH receptor type 1 in bone cells. Journal of Cellular Physiology, v. 240, n. 1, 2025. DOI: https://doi.org/10.1002/jcp.70067

HIFNAWY, M. S. et al. Nature-inspired male contraceptive and spermicidal products. Phytochemistry Reviews, v. 20, p. 797–843, 2020.

JOHNSTON, D.; GOLDBERG, E. Preclinical contraceptive development for men and women. Biology of Reproduction, v. 103, n. 2, p. 147–156, 2020. DOI: https://doi.org/10.1093/biolre/ioaa076

KARANWAL, S. et al. Higher abundance of DLD protein in buffalo bull spermatozoa causes elevated ROS production leading to early sperm capacitation and reduction in fertilizing ability. Journal of Animal Science and Biotechnology, v. 15, n. 1, 2024. DOI: https://doi.org/10.1186/s40104-024-01085-6

KARTHIKEYAN, S. et al. Statin drugs and lipid modulation: mechanistic basis considering lipid rafts, kinase signaling, myopathy, and cancer. Pharmacological Research, p. 107912, 2025. DOI: https://doi.org/10.1016/j.phrs.2025.107912

KENT, K. et al. Toward development of the male pill: a decade of potential non-hormonal contraceptive targets. Frontiers in Cell and Developmental Biology, v. 8, p. 61, 2020. DOI: https://doi.org/10.3389/fcell.2020.00061

KHAMAMKAR, A. et al. Disrupting sperm maturation: a non-hormonal contraceptive approach, targeting GSK3α in the epididymal spermatozoa. Human Reproduction, v. 40, supl. 1, 2025. DOI: https://doi.org/10.1093/humrep/deaf097.353

KIM, K. J.; JEON, Y. J.; LEE, S. H. Anti-obesity effects of fucoidan. Journal of Nutritional Biochemistry, v. 25, n. 5, p. 456–463, 2014. DOI: https://doi.org/10.1016/j.jnutbio.2013.12.006

LASTRA-VARGAS, L. M. et al. Endogenous ouabain: a possible link between high salt intake and male infertility. Reproductive System & Sexual Disorders: Current Research, v. 10, p. 1–4, 2021. DOI: https://doi.org/10.35248/2161-038X.21.10.256

LEE, K.; HWANG, J. Ca2+ homeostasis and male fertility: a target for a new male contraceptive system. Animal Cells and Systems, v. 28, n. 4, p. 171–183, 2024. DOI: https://doi.org/10.1080/19768354.2024.2345647

LEE, S. et al. 17BIPHE2, an engineered cathelicidin antimicrobial peptide with low susceptibility to proteases, is an effective spermicide and microbicide against Neisseria gonorrhoeae. Human Reproduction, 2022. DOI: https://doi.org/10.1093/humrep/deac188

LI, B.; LU, F.; WEI, X.; ZHAO, R. Fucoidan: structure and bioactivity. Molecules, v. 13, n. 8, p. 1671–1695, 2008. DOI: https://doi.org/10.3390/molecules13081671

MARIANI, N. et al. Advances in non-hormonal male contraception targeting sperm motility. Human Reproduction Update, v. 29, n. 5, 2023. DOI: https://doi.org/10.1093/humupd/dmad008

MATEO-OTERO, Y. et al. Embryo development is impaired by sperm mitochondrial-derived ROS. Biological Research, v. 57, n. 1, 2024. DOI: https://doi.org/10.1186/s40659-024-00483-4

MCDERMOTT, J. P. et al. Green fluorescence protein driven by the Na,K-ATPase α4 isoform promoter is expressed only in male germ cells of mouse testis. Journal of Assisted Reproduction and Genetics, v. 29, n. 12, p. 1313–1325, 2012. DOI: https://doi.org/10.1007/s10815-012-9876-x

MCDERMOTT, J. P. et al. Na,K-ATPase α4, and not Na,K-ATPase α1, is the main contributor to sperm motility, but its high ouabain binding affinity site is not required for male fertility in mice. Journal of Membrane Biology, v. 254, n. 5, p. 549–561, 2021. DOI: https://doi.org/10.1007/s00232-021-00181-2

MILEWSKI, D.; JAMES, P. Alpha4 Na,K-ATPase localization and expression are dynamic aspects of spermatogenesis and in sperm incubated under capacitating conditions. International Journal of Molecular Sciences, v. 26, n. 5, p. 1817, 2025. DOI: https://doi.org/10.3390/ijms26051817

MO, L. et al. The mechanism of oxidative stress in asthenozoospermia and antioxidant strategies: a review. Frontiers in Endocrinology, v. 16, p. 1670762, 2025. DOI: https://doi.org/10.3389/fendo.2025.1670762

OISHEE, M. et al. Na+,K+-ATPase α isoforms in sperm show a highly structured and distinct pattern of distribution. Reproduction, v. 170, n. 3, 2025. DOI: https://doi.org/10.1530/rep-25-0114

OLIVEIRA, J. et al. Glycerol kinase 2 as a metabolic sentinel for human sperm motility and male fertility. Biomolecules, v. 15, n. 9, p. 1249, 2025. DOI: https://doi.org/10.3390/biom15091249

PATANKAR, M. S. et al. A revised structure for fucoidan may explain some of its biological activities. Journal of Biological Chemistry, v. 268, n. 29, p. 21770–21776, 1993.

PRACTICE COMMITTEE OF THE AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE. Combined hormonal contraception and the risk of venous thromboembolism: a guideline. Fertility and Sterility, v. 107, n. 1, p. 43–51, 2017. DOI: https://doi.org/10.1016/j.fertnstert.2016.09.027

PRADHAN, B. et al. Multifunctional role of fucoidan, sulfated polysaccharides in human health and disease: a journey under the sea in pursuit of potent therapeutic agents. International Journal of Biological Macromolecules, v. 164, p. 4263–4278, 2020. DOI: https://doi.org/10.1016/j.ijbiomac.2020.09.019

QIU, S. et al. Bioactive polysaccharides from red seaweed as potent food supplements: a systematic review of their extraction, purification, and biological activities. Carbohydrate Polymers, v. 275, p. 118696, 2022. DOI: https://doi.org/10.1016/j.carbpol.2021.118696

RAJASEKARAN, M. et al. Spermicidal activity of an antifungal saponin obtained from the tropical herb Mollugo pentaphylla. Contraception, v. 47, n. 4, p. 401–412, 1993. DOI: https://doi.org/10.1016/0010-7824(93)90037-8

REN, D. et al. Hypolipidemic effects of fucoidan fractions from Saccharina sculpera (Laminariales, Phaeophyceae). International Journal of Biological Macromolecules, v. 140, p. 188–195, 2019. DOI: https://doi.org/10.1016/j.ijbiomac.2019.08.002

RITHAPORN, T.; MONGA, M.; RAJASEKARAN, M. Curcumin: a potential vaginal contraceptive. Contraception, v. 68, n. 3, p. 219–223, 2003. DOI: https://doi.org/10.1016/s0010-7824(03)00163-x

RUZZI, F. et al. Lipid rafts, caveolae, and epidermal growth factor receptor family: friends or foes? Cell Communication and Signaling, v. 22, n. 1, 2024. DOI: https://doi.org/10.1186/s12964-024-01876-4

SABRI, H. et al. The yin and yang of sodium lauryl sulfate use for oral and periodontal health: a literature review. Journal of Dentistry, v. 24, p. 262–276, 2023. DOI: https://doi.org/10.30476/dentjods.2022.95108.1836

SALICIONI, A. et al. Testis-specific serine kinase protein family in male fertility and as targets for non-hormonal male contraception. Biology of Reproduction, v. 103, n. 2, p. 264–274, 2020. DOI: https://doi.org/10.1093/biolre/ioaa064

SANJEEWA, K. et al. Anti-inflammatory mechanisms of fucoidans to treat inflammatory diseases: a review. Marine Drugs, v. 19, 2021. DOI: https://doi.org/10.3390/md19120678

SENGUPTA, P. et al. Oxidative stress affects sperm health and fertility—time to apply facts learned at the bench to help the patient: lessons for busy clinicians. Reproductive Medicine and Biology, v. 23, n. 1, 2024. DOI: https://doi.org/10.1002/rmb2.12598

SONG, X. X. et al. Effect of monosaccharide L-fucose and polysaccharide fucoidan on sperm α-L-fucosidase activity and relation to sperm-oocyte interaction in pig. Asian-Australasian Journal of Animal Sciences, v. 20, n. 3, p. 351–358, 2007. DOI: https://doi.org/10.5713/ajas.2007.351

SUTYAK, K. et al. Spermicidal activity of the safe natural antimicrobial peptide subtilosin. Infectious Diseases in Obstetrics and Gynecology, 2008. DOI: https://doi.org/10.1155/2008/540758

SYEDA, S. et al. Strategies to develop Na,K-ATPase-α4 inhibitors as male contraceptives. International Journal of Molecular Sciences, v. 26, n. 12, p. 5646, 2025. DOI: https://doi.org/10.3390/ijms26125646

SYEDA, S. S. et al. The Na+ and K+ transport system of sperm (ATP1A4) is essential for male fertility and an attractive target for male contraception. Biology of Reproduction, v. 103, n. 2, p. 343–356, 2020. DOI: https://doi.org/10.1093/biolre/ioaa093

TANPHAICHITR, N. et al. Potential use of antimicrobial peptides as vaginal spermicides/microbicides. Pharmaceuticals, v. 9, 2016. DOI: https://doi.org/10.3390/ph9010013

THUNDATHIL, J. C.; RAJAMANICKAM, G. D.; KASTELIC, J. P. Na/K-ATPase and regulation of sperm function. Animal Reproduction, v. 15, supl. 1, p. 711–720, 2018. DOI: https://doi.org/10.21451/1984-3143-AR2018-0024

WANG, T. et al. Core fucosylation regulates the ovarian response via FSH receptor during follicular development. Journal of Advanced Research, v. 67, p. 105–120, 2024. DOI: https://doi.org/10.1016/j.jare.2024.01.025

WANG, Y.; FU, X.; LI, H. Mechanisms of oxidative stress-induced sperm dysfunction. Frontiers in Endocrinology, v. 16, p. 1520835, 2025. DOI: https://doi.org/10.3389/fendo.2025.1520835

WOO, A. L.; JAMES, P. F.; LINGREL, J. B. Sperm motility is dependent on a unique isoform of the Na,K-ATPase. Journal of Biological Chemistry, v. 275, n. 27, p. 20693–20699, 2000. DOI: https://doi.org/10.1074/jbc.M002323200

WORLD HEALTH ORGANIZATION. WHO laboratory manual for the examination and processing of human semen. 6. ed. Geneva: WHO, 2021.

WU, Y. et al. A high-resolution N-glycoproteome landscape of aging mouse ovary. Redox Biology, v. 81, p. 103584, 2025. DOI: https://doi.org/10.1016/j.redox.2025.103584

XU, M. et al. Effects of nonoxynol-9 (N-9) on sperm functions: systematic review and meta-analysis. Reproduction and Fertility, v. 3, n. 1, p. R19–R33, 2022. DOI: https://doi.org/10.1530/RAF-21-0024

XU, Z. et al. Mitochondrial regulation of spermatozoa function: metabolism, oxidative stress and therapeutic insights. Animals, v. 15, n. 15, p. 2246, 2025. DOI: https://doi.org/10.3390/ani15152246

YANG, Y. H. et al. Relationship between ouabain and asthenozoospermia. Journal of Huazhong University of Science and Technology [Medical Sciences], v. 34, n. 1, p. 87–90, 2014. DOI: https://doi.org/10.1007/s11596-014-1236-x

YE, W. et al. Spin and wavelength multiplexed nonlinear metasurface holography. Nature Communications, v. 7, n. 1, p. 11930, 2016. DOI: https://doi.org/10.1038/ncomms11930

YONIS, H. et al. Association of contemporary hormonal contraception and the risk of arterial thrombosis. European Heart Journal, v. 45, supl. 2, 2024. DOI: https://doi.org/10.1093/eurheartj/ehae666.1535

ZAHARIEV, N.; KATSAROV, P.; LUKOVA, P.; PILICHEVA, B. Fucoidan pharmaceutical formulations. Polymers, v. 15, n. 15, p. 3242, 2023. DOI: https://doi.org/10.3390/polym15153242

ZAYED, A. et al. Phenomenological investigation of the cytotoxic activity of fucoidan isolated from Fucus vesiculosus. Process Biochemistry, v. 84, p. 158–165, 2019.

ZHANG, R. et al. Proteomics and metabolomics analyses of mechanism underlying bovine sperm cryoinjury. BMC Genomics, v. 26, n. 1, p. 11258, 2025. DOI: https://doi.org/10.1186/s12864-025-11258-w

ZHERNOV, Y. V. et al. Microbicides for topical HIV immunoprophylaxis: current status and future prospects. Pharmaceuticals (Basel, Switzerland), v. 17, n. 6, p. 668, 2024. DOI: https://doi.org/10.3390/ph17060668

ZHU, Z. et al. Negative effects of ROS generated during linear sperm motility on gene expression and ATP generation in boar sperm mitochondria. Free Radical Biology and Medicine, v. 141, p. 159–171, 2019. DOI: https://doi.org/10.1016/j.freeradbiomed.2019.06.018

Cómo citar

Pedras Silva, P. G., de Oliveira Correa, M. ., Vilela de Morais, H. ., Correia Casotti, M. ., de Paula, F. ., Drumond Louro, I. ., Valentim Nogueira, B., & Dummer Meira, D. . (2026). INHIBICIÓN SINÉRGICA DE LA FUNCIÓN ESPERMÁTICA HUMANA POR FUCOIDAN Y OUABAÍNA REVELA UNA POTENTE ESTRATEGIA ANTICONCEPTIVA NO HORMONAL. RECIMA21 - Revista Científica Multidisciplinar - ISSN 2675-6218, 7(4), e747515. https://doi.org/10.47820/recima21.v7i4.7515