Article Data

  • Views 1919
  • Dowloads 66

Original Research

Open Access

Zinc alleviates high fat diet-induced spermatogenic dysfunction in Wistar rats: role of oxidative stress, HMGB1 and inflammasome

El zinc alivia la disfunción espermatogénica inducida por una dieta rica en grasas en ratas Wistar: papel del estrés oxidativo, HMGB1 y el inflamasoma

  • Eman Hamed Elmorsy1
  • Rania Gaber Aly2
  • Noha Mohamed Badae3
  • Mona Mohamed Aboghazala4
  • Salma Samir Omar1,*,

1Department of Dermatology, Venereology & Andrology, Faculty of Medicine, Alexandria University, 21521 Alexandria, Egypt

2Department of Pathology, Faculty of Medicine, Alexandria University, 21521 Alexandria, Egypt

3Department of Medical Physiology, Faculty of Medicine, Alexandria University, 21521 Alexandria, Egypt 4Ministry of Health Hospitals, 21527 Alexandria, Egypt

DOI: 10.22514/j.androl.2024.007 Vol.22,Issue 1,March 2024 pp.44-52

Submitted: 26 November 2023 Accepted: 25 January 2024

Published: 30 March 2024

*Corresponding Author(s): Salma Samir Omar E-mail: salma.samir@alexmed.edu.eg

Abstract

Whether chronic inflammation in the genital tract induced by obesity shares in spermatogenic dysfunction is not clearly known. We aimed to study the effect of high fat diet (HFD) on spermatogenesis, seminal oxidative stress (malondialdehyde (MDA)) and inflammatory markers (high mobility group box 1 (HMGB1), nucleotide-binding oligomerization domain, leucine rich repeat and pyrin-3 domain containing (NLRP3)) in the rat testes and the role of zinc on testicular dysfunction and chronic inflammation in high fat diet (HFD) fed rat testes. This parallel group comparative experimental study included 36 male wistar rats divided into 3 groups: group A (fed on normal control diet); group B (fed on high fat diet (HFD) only); and group C (fed on HFD with zinc supplementation 3.2 mg/kg/day orally). At the end of the 12th week, sperm count, viability and motility were assessed by computer-assisted seemen analysis (CASA), seminal malondialdehyde measured by calorimetry and histopathological examination of testicular sections was done. Immunohistochemical staining was done for HMGB1 and NLRP3 evaluation. Sperm count was lowest in group B. Groups A and C showed statistically significant higher mean sperm vitality, total and progressive motility scores (p < 0.001), while no difference was found between the groups A and C (p > 0.05). Seminal malondialdehyde level was significantly highest in group B. Tubular diameter, epithelial height and Johnsen score were significantly lowest in group B. Significantly higher HMGB1 and NLRP3 levels were demonstrated in group B (p < 0.001). Obesity is associated with testicular dysfunction, testicular oxidative stress and increased testicular HMGB1 and NLRP3. We suggest a beneficial effect of zinc on testicular function in HFD-rats.


Resumen

No se sabe claramente si la inflamación crónica en el tracto genital inducida por la obesidad participa en la disfunción espermatogénica. Nuestro objetivo fue estudiar el efecto de una dieta alta en grasas sobre la espermatogénesis, el estrés oxidativo seminal y los marcadores inflamatorios en los testículos de ratas y el papel del zinc en la disfunción testicular y la inflamación crónica en una dieta alta en grasas testículos de ratas alimentadas. Este estudio experimental comparativo incluyó 36 ratas wistar macho divididas en 3 grupos: grupo A (alimentadas con una dieta de control); grupo B (alimentados únicamente con una dieta alta en grasas); y el grupo C (alimentado con dieta alta en grasas con suplementación de zinc). Se evaluó el recuento, la vitalidad y la motilidad de los espermatozoides mediante un sistema análisis de semen asistido por computadora, se midió el malondialdehído seminal mediante calorimetría y se realizó un examen histopatológico de las secciones testiculares. Se realizó tinción inmunohistoquímica para la evaluación de (grupo de cajas de movilidad alta 1, inflamasoma 3). Los grupos A y C mostraron puntuaciones medias estadísticamente significativas más altas de vitalidad espermática, motilidad total y progresiva, mientras que no se encontraron diferencias entre los grupos A y C. El nivel de malondialdehído seminal fue significativamente más alto en el grupo B. El diámetro tubular, la altura epitelial y la puntuación de Johnsen fueron significativamente más bajos en el grupo B. Se demostraron niveles significativamente más altos de HMGB1 y NLRP3 en el grupo B. Sugerimos un efecto beneficioso del zinc sobre la función testicular en ratas HFD.


Keywords

Obesity; Male infertility; Inflammasome; HMGB1; Oxidative stress; Zinc


Palabras Clave

Obesidad; Infertilidad masculina; Inflamasoma; HMGB1; Estrés oxidativo; Zinc


Cite and Share

Eman Hamed Elmorsy,Rania Gaber Aly,Noha Mohamed Badae,Mona Mohamed Aboghazala,Salma Samir Omar. Zinc alleviates high fat diet-induced spermatogenic dysfunction in Wistar rats: role of oxidative stress, HMGB1 and inflammasomeEl zinc alivia la disfunción espermatogénica inducida por una dieta rica en grasas en ratas Wistar: papel del estrés oxidativo, HMGB1 y el inflamasoma. Revista Internacional de Andrología. 2024. 22(1);44-52.

References

[1] Fan W, Xu Y, Liu Y, Zhang Z, Lu L, Ding Z. Obesity or overweight, a chronic inflammatory status in male reproductive system, leads to mice and human subfertility. Frontiers in Physiology. 2018; 8: 1117.

[2] Esmail M, Kandeil M, El-Zanaty AM, Abdel-Gabbar M. The ameliorative effect of atorvastatin on serum testosterone and testicular oxidant/antioxidant system of HFD-fed male albino rats. F1000Research. 2020; 9: 1300.

[3] Jia Y, Feng Q, Ge Z, Guo Y, Zhou F, Zhang K, et al. Obesity impairs male fertility through long-term effects on spermatogenesis. BMC Urology. 2018; 18: 42.

[4] Russo AJ, Mensah A, Bowman J. Increased Hmgb1 associated with low zinc and symptom severity in children with autism. Advances in Neurology and Neuroscience. 2020; 3: 45–48.

[5] Geng Y, Ma Q, Liu YN, Peng N, Yuan FF, Li XG, et al. Heatstroke induces liver injury via IL-1beta and HMGB1-induced pyroptosis. Journal of Hepatology. 2015; 63: 622–633.

[6] Tavalaee M, Rahmani M, Drevet JR, Nasr-Esfahani MH. The NLRP3 inflammasome: molecular activation and regulation in spermatogenesis and male infertility; a systematic review. Basic and Clinical Andrology. 2022; 32: 8.

[7] Poli G, Fabi C, Sugoni C, Bellet MM, Costantini C, Luca G, et al. The role of NLRP3 inflammasome activation and oxidative stress in varicocoele-mediated male hypofertility. International Journal of Molecular Sciences. 2022; 23: 5233.

[8] Walenta L, Schmid N, Schwarzer JU, Köhn F, Urbanski HF, Behr R, et al. NLRP3 in somatic non-immune cells of rodent and primate testes. Reproduction. 2018; 156: 231–238.

[9] Gao Z, Liang Y, Yang S, Zhang T, Gong Z, Li M, et al. Bariatric surgery does not improve semen quality: evidence from a meta-analysis. Obesity Surgery. 2022; 32: 1341–1350.

[10] Zhang W, Tian Z, Qi X, Chen P, Yang Q, Guan Q, et al. Switching from high-fat diet to normal diet ameliorate BTB integrity and improve fertility potential in obese male mice. Scientific Reports. 2023; 13: 14152.

[11] Nematollahi A, Kazeminasab F, Tavalaee M, Marandi SM, Ghaedi K, Nazem MN, et al. Effect of aerobic exercise, low-fat and high‐fat diet on the testis tissue and sperm parameters in obese and nonobese mice model. Andrologia. 2019; 51: e13273.

[12] Crean AJ, Pulpitel TJ, Pini T, Rickard JP, de Graaf SP, Senior AM, et al. Low-fat, high-carbohydrate diets reduce body weight and sperm count but increase sperm motility in mice. The Journal of Nutrition. 2024; 154: 60–68.

[13] Prasad AS, Bao B. Molecular mechanisms of zinc as a pro-antioxidant mediator: clinical therapeutic implications. Antioxidants. 2019; 8: 164.

[14] Abozaid ER, Hany A, Kattawy El. Vitamin D3 nanoemulsion ameliorates testicular dysfunction in high-fat diet-induced obese rat model. The Medical Journal of Cairo University. 2020; 88: 775–785.

[15] Yin Y, Yu Z, Xia M, Luo X, Lu X, Ling W. Vitamin D attenuates high fat diet—induced hepatic steatosis in rats by modulating lipid metabolism. European Journal of Clinical Investigation. 2012; 42: 1189–1196.

[16] Ma J, Han R, Li Y, Cui T, Wang S. The mechanism of zinc sulfate in improving fertility in obese rats analyzed by sperm proteomic analysis. BioMed Research International. 2020; 2020: 9876363.

[17] Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry. 1979; 95: 351–358.

[18] Thanh TN, Van PD, Cong TD, Minh TL, Vu QHN. Assessment of testis histopathological changes and spermatogenesis in male mice exposed to chronic scrotal heat stress. Journal of Animal Behaviour and Biometeorology. 2020; 8: 174–180.

[19] Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. The Lancet. 2014; 384: 766–781.

[20] Bakos HW, Henshaw RC, Mitchell M, Lane M. Paternal body mass index is associated with decreased blastocyst development and reduced live birth rates following assisted reproductive technology. Fertility and Sterility. 2011; 95: 1700–1704.

[21] Naomi R, Teoh SH, Embong H, Balan SS, Othman F, Bahari H, et al. The role of oxidative stress and inflammation in obesity and its impact on cognitive impairments—a narrative review. Antioxidants. 2023; 12: 1071.

[22] Fernández-Sánchez A, Madrigal-Santillán E, Bautista M, Esquivel-Soto J, Morales-González A, Esquivel-Chirino C, et al. Inflammation, oxidative stress, and obesity. International Journal of Molecular Sciences. 2011; 12: 3117–3132.

[23] Ibáñez CA, Erthal RP, Ogo FM, Peres MNC, Vieira HR, Conejo C, et al. A high fat diet during adolescence in male rats negatively programs reproductive and metabolic function which is partially ameliorated by exercise. Frontiers in Physiology. 2017; 8: 807.

[24] Erdemir F, Atilgan D, Markoc F, Boztepe O, Suha-Parlaktas B, Sahin S. The effect of diet induced obesity on testicular tissue and serum oxidative stress parameters. Actas UrolóGicas EspañOlas. 2012; 36: 153–159.

[25] Liu Y, Zhao W, Gu G, Lu L, Feng J, Guo Q, et al. Palmitoyl‐protein thioesterase 1 (PPT1): an obesity-induced rat testicular marker of reduced fertility. Molecular Reproduction and Development. 2014; 81: 55–65.

[26] Leisegang K, Sengupta P, Agarwal A, Henkel R. Obesity and male infertility: mechanisms and management. Andrologia. 2021; 53: e13617.

[27] Bhardwaj JK, Panchal H, Saraf P. Ameliorating effects of natural antioxidant compounds on female infertility: a review. Reproductive Sciences. 2021; 28: 1227–1256.

[28] Dutta S, Sengupta P, Slama P, Roychoudhury S. Oxidative stress, testicular inflammatory pathways, and male reproduction. International Journal of Molecular Sciences. 2021; 22: 10043.

[29] Aslani F, Schuppe H, Guazzone VA, Bhushan S, Wahle E, Lochnit G, et al. Targeting high mobility group box protein 1 ameliorates testicular inflammation in experimental autoimmune orchitis. Human Reproduction. 2015; 30: 417–431.

[30] Arab HH, Elhemiely AA, El-Sheikh AAK, Khabbaz HJA, Arafa EA, Ashour AM, et al. Repositioning linagliptin for the mitigation of cadmium-induced testicular dysfunction in rats: targeting HMGB1/TLR4/NLRP3 axis and autophagy. Pharmaceuticals. 2022; 15: 852.

[31] Minutoli L, Antonuccio P, Irrera N, Rinaldi M, Bitto A, Marini H, et al. NLRP3 inflammasome involvement in the organ damage and impaired spermatogenesis induced by testicular ischemia and reperfusion in mice. Journal of Pharmacology and Experimental Therapeutics. 2015; 355: 370–380.

[32] Minutoli L, Puzzolo D, Rinaldi M, Irrera N, Marini H, Arcoraci V, et al. ROS-mediated NLRP3 inflammasome activation in brain, heart, kidney, and testis ischemia/reperfusion injury. Oxidative Medicine and Cellular Longevity. 2016; 2016: 2183026.

[33] Mu Y, Yin T, Zhang Y, Yang J, Wu Y. Diet-induced obesity impairs spermatogenesis: the critical role of NLRP3 in Sertoli cells. Inflammation and Regeneration. 2022; 42: 24.

[34] Kehinde E, Anim J, Oriowo M, Memon A, Omu A, Al-Azemi M, et al. Molecular basis for the effects of zinc deficiency on spermatogenesis: an experimental study in the Sprague-dawley rat model. Indian Journal of Urology. 2015; 31: 57–64.

[35] Olechnowicz J, Tinkov A, Skalny A, Suliburska J. Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism. The Journal of Physiological Sciences. 2018; 68: 19–31.

[36] Fallah A, Mohammad-Hasani A, Colagar AH. Zinc is an essential element for male fertility: a review of Zn roles in men’s health, germination, sperm quality, and fertilization. Journal of Reproduction & Infertility. 2018; 19: 69–81.

[37] Aziz NM, Kamel MY, Mohamed MS, Ahmed SM. Antioxidant, anti-inflammatory, and anti-apoptotic effects of zinc supplementation in testes of rats with experimentally induced diabetes. Applied Physiology, Nutrition, and Metabolism. 2018; 43: 1010–1018.

[38] Hewlings S, Kalman D. A review of zinc-l-carnosine and its positive effects on oral mucositis, taste disorders, and gastrointestinal disorders. Nutrients. 2020; 12: 665.

[39] Ooi TC, Chan KM, Sharif R. Antioxidant, anti-inflammatory, and genomic stability enhancement effects of zinc l-carnosine: a potential cancer chemopreventive agent? Nutrition and Cancer. 2017; 69: 201–210.

[40] Ooi TC, Chan KM, Sharif R. Zinc L-carnosine inhibits the secretion of pro-inflammatory HMGB1 protein from lipopolysaccharide-induced RAW 264.7 murine macrophage. To be published in Research Square. 2021. [Preprint].

[41] Siddiqui S, Dhar C, Sundaramurthy V, Sasmal A, Yu H, Bandala-Sanchez E, et al. Acidosis, zinc and HMGB1 in sepsis: a common connection involving sialoglycan recognition. BioRxiv. 2020.

[42] Siddiqui SS, Dhar C, Sundaramurthy V, Sasmal A, Yu H, Bandala-Sanchez E, et al. Sialoglycan recognition is a common connection linking acidosis, zinc, and HMGB1 in sepsis. Proceedings of the National Academy of Sciences. 2021; 118: e2018090118.

[43] Summersgill H, England H, Lopez-Castejon G, Lawrence CB, Luheshi NM, Pahle J, et al. Zinc depletion regulates the processing and secretion of IL-1β. Cell Death & Disease. 2014; 5: e1040.

[44] Fan Y, Zhang X, Yang L, Wang J, Hu Y, Bian A, et al. Zinc inhibits high glucose-induced NLRP3 inflammasome activation in human peritoneal mesothelial cells. Molecular Medicine Reports. 2017; 16: 5195–5202.


Top