Universität zu Köln

Omrani, Sara ORCID: 0009-0003-6851-7874 (2026). Effects of scrotal hyperthermia on inducing signaling pathways of Alkaliptosis and Oxeiptosis in testicular tissue of adult male mice. PhD thesis, Universität zu Köln.

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Abstract

Background: Alkaliptosis and Oxeiptosis are important pathways in cell-death regulation, which can be induced by exposing to high temperature. Alkaliptosis is a pH-dependent form of regulated cell death driven by activation of the IKBKB-NF-B pathway-dependent downregulation of CA9. On the other hand, Oxeiptosis is a novel oxygen radical-induced caspase-independent regulated cell death driven by the activation of the KEAP1-PGAM5-AIFM1 pathway. The objective of this study was to examine the effects of scrotal hyperthermia on the induction of Alkaliptosis and Oxeiptosis molecular pathways, and its influence on testicular tissue and sperm analysis in adult male mice. Method: In the present study, 20 adult male mice weighing 25-30 g were randomly divided into two groups, a hyperthermia group and a control group. Each animal in the hyperthermia group is induced by scrotal hyperthermia at 43°C for 20 minutes. At the end of the experimental period, serum testosterone, sperm analyses including sperm concentration, motility, survival, morphology, and testicular histological studies such as stereoscopic examination and non-apoptotic cell death were performed in both groups. In addition, the expression of genes involved in the alkaliptosis (IKBKB-NF-κB and CA9) and oxeiptosis (KEAP1, PGAM5, and AIFM1) molecular pathways was analyzed using real-time PCR. Results: In the hyperthermia group, the total sperm count and the percentage of sperm exhibiting normal motility, viability, and morphology were significantly lower than those in the control group (P<0.001). Additionally, serum testosterone measurements revealed a significant reduction in the hyperthermia group (P<0.001). Testis volume, length of seminiferous tubules, and the number of testicular cells were also significantly decreased in the hyperthermia group compared to the control group (P<0.001). Assessment of the gene expression in the Oxeiptosis and Alkaliptosis pathways revealed the following findings. In the Alkaliptosis pathway, there was a notable increase in the relative expression of NF-κB (P<0.001), while the relative expression of CA9 exhibited a significant decrease (P<0.0001) in the scrotal hyperthermia group when compared to the control group. For the IKBKB gene, the relative expression showed no significant difference between scrotal hyperthermia and control groups. Considering Oxeiptosis pathway, the AIFM1 gene showed a significant decrease in the scrotal hyperthermia group compared to the control group (P<0.001). While, the relative expression of KEAP1 and PGAM5 genes demonstrated a significant increase (P<0.001 and P<0.0001 respectively) in the scrotal hyperthermia group compared to the control group. Conclusion: Real-time PCR analysis revealed a remarkable deregulation in the gene expression pattern of Oxeiptosis and Alkaliptosis markers. Therefore, it can be concluded that scrotal11 hyperthermia can induce non-apoptotic cell death and activate the signaling pathways associated with Oxeiptosis and Alkaliptosis

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Omrani, Sara saraomrani1373@yahoo.com https://orcid.org/0009-0003-6851-7874 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-797945
Date:	2026
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Frauenheilkunde > Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language scrotal hyperthermia English Oxeiptosis English Alkaliptosis English
Date of oral exam:	9 December 2025
Referee:	Name Academic Title Rahimi, Gohar Professorin Dr. med. Kashkar, Hamid Universitätsprofessor Dr. rer. nat.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/79794