P-032 Exploration of the common genetic landscape of COVID-19 and male infertility
Authors: Chen Y , Yuan P , Liu C 
Published: June 2023

Abstract

Study question
What is the cross-talk molecular mechanisms between COVID-19 and male infertility?

Summary answer
The present study identified and validated hub COVID-19-related differentially expressed genes (CORGs) in COVID-19 and male infertility, and systematically explored molecular interactions and regulatory features.

What is known already
COVID-19 has spread widely across continents since 2019, causing serious damage to human health. Accumulative research uncovered that SARS-CoV-2 poses a great threat to male fertility. SARS-CoV-2 has been confirmed to exist in semen specimens and seminiferous tubes in the testes of male COVID-19 patients. COVID-19 had an unfavorable influence on the semen parameters in infertile men, including sperm count, motility, and morphology. Male infertility (MI) is a common comorbidity for the COVID-19 pandemic.

Study design, size, duration
The study included the bioinformatic calculation, participant recruitment, specimen collection, and experimental validation in the university hospital.

Participants/materials, setting, methods
Four transcriptome data regarding COVID-19 and male infertility were downloaded from the GEO repository, and were divided for initial analysis and external validation. Differentially expressed genes analysis, GO and pathway annotation, PPI network, connectivity ranking, ROC analysis, and immune infiltration were performed to gain hub CORGs. We recorded medical information of COVID-19 patients with male infertility and matched controls, and harvested their sperm samples. Expressions of hub CORGs were detected through the qRT-PCR technique.

Main results and the role of chance
We identified 460 overlapped CORGs in both the COVID-19 differentially expressed genes (DEGs) and MI DEGs. CORGs were significantly enriched in DNA damage and repair-associated, cell cycle-associated, ubiquitination-associated, and coronavirus-associated signaling. Module assessment of PPI network revealed that enriched GO functions were closely related to cell cycle and DNA metabolism processes. Pharmacologic agent prediction displayed protein-drug interactions of ascorbic acid, biotin, caffeine, and L-cysteine with CORGs. After connectivity ranking and external validation, three hub CORGs (ENTPD6, CIB1, and EIF3B) showed good diagnostic performance (area under the curve &gt; 0.75). Subsequently, three types of immune cells (CD8+ T cells, monocytes, and macrophages M0) were dominantly enriched, and 24 transcription factor-CORGs interactions and 13 miRNA-CORGs interactions were constructed in the network. Finally, qRT-PCR analysis confirmed that there were significant differences in the expression of hub CORGs (CIB1 and EIF3B) between the patient and control groups.

Limitations, reasons for caution
Diverse sequencing platforms and different ethnic subjects in the genetic data have influence on the accuracy of our analysis to some extent.

Wider implications of the findings
It is the first time for us to mine the genetic interrelationship between COVID-19 and male infertility. Our study provided new clues for the pathogenesis of these two diseases, and shared emerging potential biomarkers and drug targets for COVID-19-associated male infertility.

Trial registration number
National Natural Science Foundation of China (No. 82201758, No. 81700667, and No. 82201775)