Cross-talk between inflammatory markers, cytokines, and growth factors in varicocele; emphasis on testicular macrophages involvement

• Grant number: 21/09149-3
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: December 01, 2022
• End date: May 31, 2026
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Ricardo Pimenta Bertolla
• Grantee: Aram Minas
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated scholarship(s): 23/08009-9 - Establishment of a varicocele mouse model, and characterization of varicocele-induced inflammation in testis and epididymis; insight into immune cell infiltration, and acute and chronic chemokine and cytokine expression, BE.EP.DD

Abstract

Varicocele (VCL) multi-pathologically affects testicular tissue and sperm parameters. In addition, VCL-induced inflammation has a blatant relevance with VCL-induced oxidative stress and VCL-induced negative effects on male fertility. However, it has been revealed that the VCL increases the level of the inflammatory cytokine in both testicular tissue and seminal fluid, there is no evidence for macrophages involvement in VCL condition. Moreover, there is no recommended medicine or approach in order to face VCL-induced inflammation. Thus, it is essential to fully understand the VCL-induced inflammation origin and effects in VCL-induced animal models as well as VCL patients. Moreover, it is important to investigate testicular macrophage involvement and possible useable medicines in order to face this condition in patients with VCL. The main hypothesizes of this study are to follow up on VCL-induced inflammatory cytokines changes in a time-dependent manner in VCL-induced rats, evaluate testicular macrophages involvement in VCL condition, the inflammatory cytokines change effects on growth factors production, and possible medicine usage to inhibit VCL-induced inflammation. In order to perform the current study, we will have a 4 step study including (I) A time-dependently examination of the VCL condition using rat animal model, (II) A cell culture study of testicular somatic cells changes in VCL-induced inflammation mimic condition and examination of our selective medicine in cell culture condition, (III) A in vivo study, using VCL-induced rats in order to evaluate our selected anti-inflammatory efficiency in in vivo condition and also analyze possible effective time after usage, (IV) Finally, in the last stage of our study, we will use semen samples in order to follow up on inflammatory cytokines changes in semen and compare their results with animal model samples to find out any possible correlation between them. Moreover, we are going to investigate any possible relationship between semen cytokines level, embryo quality and embryo development in VCL patients. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MINAS, ARAM; RAZI, MAZDAK; NASR-ESFAHANI, MOHAMMAD HOSSEIN; HASHEMI-ASL, SEYED MOHAMMAD; TAVALAEE, MARZIYEH. Oxidative Stress and Cell Cycle Arrest in Seminiferous Tubules Nearby Varicose Vessels: New Perspectives from Experimental Varicocele. REPRODUCTIVE SCIENCES, v. 30, n. 8, p. 15-pg., 2023-02-23. (21/09149-3)

MINAS, ARAM; MAHMOUDABADI, SINA; GAMCHI, NAEIMEH SHAMSI; ANTONIASSI, MARIANA PEREIRA; ALIZADEH, ARASH; BERTOLLA, RICARDO PIMENTA. Testicular torsion in vivo models: Mechanisms and treatments. ANDROLOGY, v. N/A, p. 19-pg., 2023-03-14. (21/09149-3)

MINAS, ARAM; DUNIA-WAKED; MACIEL, VALTER LUIZ, JR.; ANTONIASSI, MARIANA P.; GUILHARDUCCI, RAQUEL; VERAS, MARIANA MATERA; BERTOLLA, RICARDO P.. SHORT AND LONG-TERM EFFECTS OF EXPERIMENTAL VARICOCELE. Fertility and Sterility, v. 122, n. 4, p. 1-pg., 2024-10-01. (23/08009-9, 21/09149-3)

MINAS, ARAM; WAKED, DUNIA; MACIEL JR, VALTER LUIZ; MIYAZAKI, MIKA ALEXIA; GUILHARDUCCI, RAQUEL LOZANO; ANTONIASSI, MARIANA PEREIRA; VERAS, MARIANA MATERA; BERTOLLA, RICARDO PIMENTA. Short and long-term effects of experimental varicocele. ANDROLOGY, v. N/A, p. 10-pg., 2025-01-13. (21/09149-3, 23/08009-9)

MINAS, ARAM; COSTA, LUCAS VASCONCELOS SOARES; MIYAZAKI, MIKA ALEXIA; ANTONIASSI, MARIANA PEREIRA. Insight toward inflammasome complex contribution to male infertility. American Journal of Reproductive Immunology, v. 90, n. 2, p. 14-pg., 2023-08-01. (21/09149-3, 21/03753-6)