VIII Premio Laboratorios Ovejero: Análisis del estrés oxidativo y del inflamasoma NLRPl3 en pacientes con baja respuesta a la estimulación ovárica

  1. Lisa Rancan
  2. Beatriz Linillos Pradillo
  3. Rocío Núñez Calonge
  4. Elena Vara
Revista:
Anales de la Real Academia de Ciencias Veterinarias

Any de publicació: 2021

Volum: 29

Número: 29

Pàgines: 100-124

Tipus: Article

Resum

Background: A wide range of pathophysiological conditions are associated with fertility issues. Oxidative stress associated with chronic low-grade inflammation has emerged as a plausible key contributor to their pathogenesis. Oxidative stress can activate the NLRP3 inflammasome which can start an inflammatory form of cell death. Low ovarian response (LOR) are patients which are characterized by having a decreased ovarian follicular pool. Although it has been associated to different diseases, an association between oxidative stress and NLRP3 activation with LOR has not been described to date. Hence, this study aimed to investigate the role of the oxidative stress and the NLRP3 inflammasome activation in LOR patients. Methods: A prospective clinical observational study involved 30 donors and 22 patients. Stimulation protocols were the same for all patients. Collection of oocyte-granulose complexes (GCs) and cumulus cells (CCs) was performed during oocyte retrieval. mRNA expression of oxidative markers and inflammasome components were analyzed by qRT-PCR. Non parametric tests were used to identify significant differences between groups and spearmen correlation to asses correlation. Results: A significantly increased mRNA expression of oxidative stress markers as well as inflammasome components and inflammatory cytokines was observed in LOR patients compared to donors. In the same manner, caspase 1, 12 and 18 were also significantly increased in our group of patients in comparison to the donor expression (p<0.0001,p=0.0008 and p=0.0003 respectively). Conclusion: Our results show higher oxidative stress expression and NLRP3 activation in patients with low ovarian reserve compared to donors suggesting an activation of the pathway and its possible involvement in the pathogenesis.

Referències bibliogràfiques

  • AboEl-Maaty, A., Shata, F., Mahmoud, M., Gabr, F. 2012. «Oxidant/ antioxidant status during foal heat in Arab mares and their relation to ovarian hormones». Asian Pacific Journal of Reproduction 1 (September): 198-202.
  • Caselles, A.B., Miro-Moran, A., Morillo Rodriguez, A., Gallardo Bolaños, J.M., Ortega-Ferrusola, C., Salido, G.M., Peña, F.J., Tapia, J.A., Aparicio, I.M. 2014. «Identification of Apoptotic Bodies in Equine Semen». Reproduction in Domestic Animals = Zuchthygiene 49 (2): 254-62.
  • Chomczynski, P., Sacchi, N. 1987. «Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate-Phenol-Chloroform Extraction». Analytical Biochemistry 162 (1): 156-59.
  • Christoffersen, M., Troedsson, M.H.T. 2017. «Inflammation and Fertility in the Mare». Reproduction in Domestic Animals = Zuchthygiene 52 Suppl 3 (august): 14-20.
  • Claes, A., Ball, B.A., Scoggin, K.E., Esteller-Vico, A., Kalmar, J.J., Conley, A.J., Squires, E.L., Troedsson, M.H.T. 2015. «The Interrelationship between Anti-Müllerian Hormone, Ovarian Follicular Populations and Age in Mares». Equine Veterinary Journal 47 (5): 537-41.
  • Cohen, J., Chabbert-Buffet, N., Darai, E. 2015. «Diminished Ovarian Reserve, Premature Ovarian Failure, Poor Ovarian Responder-- a Plea for Universal Definitions». Journal of Assisted Reproduction and Genetics 32 (12): 1709-12.
  • Di Nicuolo, F., Specchia, M., Trentavizi, L., Pontecorvi, A., Scambia, G., Di Simone, N. 2018. «An Emerging Role of Endometrial Inflammasome in Reproduction: New Therapeutic Approaches ». Protein and Peptide Letters 25 (5): 455-62.
  • D’Ippolito, S., Tersigni, C., Marana, R., Di Nicuolo, F., Gaglione, R., Rossi, E.D., Castellani, R., Scambia, G., Di Simone, N. 2016. «Inflammosome in the Human Endometrium».
  • Dusek, J., Munk, Z. 1980. «The effect of the age of stallions and mares on their fertility». Veterinarni Medicina 25 (7): 437-48. [10] El-Maaty, A.M. Abo, Ibrahim, A.M., Ezzo, O.H. 2013. «Influence of Mineral Supplementation on Oxidative Stress, Ovarian Follicles Growth and Reproductive Hormone Concentration in Cyclic Arab Mares». Asian Pacific Journal of Reproduction 2 (1): 8-14.
  • Ferrero, H., Delgado-Rosas, F., Garcia-Pascual, C.M., Monterde, M., Zimmermann, R.C., Simón, C., Pellicer, A., Gómez, R. 2012. «Efficiency and Purity Provided by the Existing Methods for the Isolation of Luteinized Granulosa Cells: A Comparative Study». Human Reproduction (Oxford, England) 27 (6): 1781-89.
  • Garcia-Velasco, J.A., Isaza, V., Caligara, C., Pellicer, A., Remohí, J., Simón, C. 2003. «Factors That Determine Discordant Outcome from Shared Oocytes». Fertility and Sterility 80 (1): 54-60.
  • Gibb, Z., Lambourne, S.R., Aitken, R.J. 2014. «The Paradoxical Relationship Between Stallion Fertility and Oxidative Stress». Biology of Reproduction 91 (3).
  • Greene, A.D., Patounakis, G., Segars, J.H. 2014. «Genetic associations with diminished ovarian reserve: a systematic review of the literature». Journal of Assisted Reproduction and Genetics 31 (8): 935-46.
  • Gupta, R.K., Patel, A.K., Shah, N., Choudhary, A.K., Jha, U.K., Yadav, U.C., Gupta, P.K., Pakuwal, U. 2014. «Oxidative Stress and Antioxidants in Disease and Cancer: A Review». Asian Pacific Journal of Cancer Prevention 15 (11): 4405-9.
  • Gheise J.E., Riasi, A., Shahneh, A.Z., Celi, P., Ghoreishi, S.M. 2017. «Effect of pre-calving body condition score and previous lactation on BCS change, blood metabolites, oxidative stress and milk production in Holstein dairy cows». Italian Journal of Animal Science 16 (3): 474-83.
  • Jirge, P.R. 2016. «Poor ovarian reserve». Journal of Human Reproductive Sciences 9 (2): 63-69.
  • Kannan, N., Jain, N. 2000. «Oxidative Stress and Apoptosis». Pathophysiology: The Official Journal of the International Society for Pathophysiology 7 (3): 153-63.
  • Kotp, M.S, Mohamed, A.H., El-Tohamy, M.M., El-Maaty, A.M Abo, El Nattat, W.S. 2015. «Oxidative Stress Biomarkers in Mares with Different Reproductive Problems», 9.
  • Kumbak, B., Oral, E., Kahraman, S., Karlikaya, G., Karagozoglu, H. 2005. «Young Patients with Diminished Ovarian Reserve Undergoing Assisted Reproductive Treatments: A Preliminary Report ». Reproductive Biomedicine Online 11 (3): 294-99.
  • Leemans, J.C., Cassel, S.L., Sutterwala, F.S. 2011. «Sensing Damage by the NLRP3 Inflammasome». Immunological Reviews 243 (1): 152-62.
  • Livak, K.J., Schmittgen, T.D. 2001. «Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2(- Delta Delta C(T)) Method». Methods (San Diego, Calif.) 25 (4):402-8.
  • Morin, S.J., Patounakis, G., Juneau, C.R., Neal, S.A., Scott, R.T., Seli, E. 2018. «Diminished Ovarian Reserve and Poor Response to Stimulation in Patients <38 Years Old: A Quantitative but Not Qualitative Reduction in Performance». Human Reproduction (Oxford, England) 33 (8): 1489-98.
  • Mossa, F., Ireland, J.J. 2019. «Physiology and Endocrinology Symposium: Anti-Müllerian Hormone: A Biomarker for the Ovarian Reserve, Ovarian Function, and Fertility in Dairy Cows». Journal of Animal Science 97 (4): 1446-55.
  • Nawito, M.F., Abd El Hameed, A.R., Sosa, A.S.A., Mahmoud, K.Gh.M. 2016. «Impact of pregnancy and nutrition on oxidant/antioxidant balance in sheep and goats reared in South Sinai, Egypt». Veterinary World 9 (8): 801-5.
  • Nuñez-Calonge, R., Cortés, S., Gutierrez Gonzalez, L.M., Kireev, R., Vara, E., Ortega, L., Caballero, P., Rancan, L., Tresguerres, J. 2016. «Oxidative Stress in Follicular Fluid of Young Women with Low Response Compared with Fertile Oocyte Donors». Reproductive BioMedicine Online 32 (4): 446-56.
  • Nuñez-Calonge, R., Rancan, L., Cortés, S., Vara, E., Andrés, C., Caballero, P., Tresguerres, J. 2019. «Apoptotic Markers and Antioxidant Enzymes Have Altered Expression in Cumulus and Granulosa Cells of Young Women with Poor Response to Ovarian Stimulation» 3 (1): 6.
  • Righi, F., Simoni, M., Malacarne, M., Summer, A., Costantini, E., Quarantelli, A. 2016. «Feeding a Free Choice Energetic Mineral- Vitamin Supplement to Dry and Transition Cows: Effects on Health and Early Lactation Performance.» Large Animal Review 22 (4): 161-70.
  • Rizzo, M., Du Preez, N., Ducheyne, K.D., Deelen, C., Beitsma, M.M., Stout, T.A.E., de Ruijter-Villani, M. 2020. «The Horse as a Natural Model to Study Reproductive Aging-Induced Aneuploidy and Weakened Centromeric Cohesion in Oocytes». Aging 12 (21): 22220-32.
  • Rizzo, M., Stout, T.A.E., Cristarella, S., Quartuccio, M., Kops, G.J.P.L., De Ruijter-Villani, M. 2021. «Compromised MPS1 Activity Induces Multipolar Spindle Formation in Oocytes From Aged Mares: Establishing the Horse as a Natural Animal Model to Study Age-Induced Oocyte Meiotic Spindle Instability». Frontiers in Cell and Developmental Biology 9: 657366.
  • Roser, J.F., Meyers-Brown, G. 2019. «Enhancing Fertility in Mares: Recombinant Equine Gonadotropins». Journal of Equine Veterinary Science 76 (may): 6-13.
  • Scoggin, C.F. 2015. «Not Just a Number: Effect of Age on Fertility, Pregnancy and Offspring Vigour in Thoroughbred Brood-Mares». Reproduction, Fertility, and Development 27 (6): 872-79.
  • Sikka, S.C. 2004. «Andrology Lab Corner*: Role of Oxidative Stress and Antioxidants in Andrology and Assisted Reproductive Technology». Journal of Andrology 25 (1): 5-18.
  • Soffler, C. 2007. «Oxidative Stress». The Veterinary Clinics of North America. Equine Practice 23 (1): 135-57.
  • Speroff, L. 1994. «The Effect of Aging on Fertility». Current Opinion in Obstetrics & Gynecology 6 (2): 115-20.
  • Stancill, J.S., Corbett, J.A. 2021. «The Role of Thioredoxin/Peroxiredoxin in the β-Cell Defense Against Oxidative Damage». Frontiers in Endocrinology 12: 718235.
  • Wang, L., Negro, R., Wu, H. 2020. «TRPM2, Linking Oxidative Stress and Ca2+ Permeation to NLRP3 Inflammasome Activation ». Current Opinion in Immunology 62 (february): 131-35.