The quality of genome is connected to human reproduction

• Applicant: Maria Krivega, Ph.D.
• Subject Area: Reproductive Medicine, Urology ; General Genetics and Functional Genome Biology ; Developmental Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 565829094

The genetic mutation underlying infertility in humans can be very different, which complicates the development of unified targeted diagnostic and eventually treatment approaches. Furthermore, the genetic basis of many infertility cases including idiopathic germ cell aplasia and rare genetic syndromes remain largely unknown, raising questions about the rationale behind genetic diagnostics. Instead, there is a pressing need to gain a deeper understanding of the common molecular mechanisms underlying pathological infertility phenotypes in humans. Previously, we showed that infertile individuals share similar disease phenotypes associated with genotoxic stress and altered Androgen Receptor (AR) expression. In the current project we would like to further explore the role of the specific signaling cascade that translates signals from degenerating genome influencing cellular physiology. It contributes to the Genotoxic Stress Phenotypes via deregulation of autophagy and the innate immune response, and telomeres maintenance in the context of human infertility. The cGAS-STING pathway plays a significant role in transmitting genotoxic stress and could be that universal molecular mechanism leading to gonadal tissue pathologies and consequent infertility in humans. While dysfunction of androgens has long been associated with infertility in both men and women, our study expands this perspective by investigating the role of androgen receptor signaling in regulating genomic integrity, with a specific focus on the involvement of the cGAS-STING pathway. This project is aimed to shift focus from excessive genetic sequencing efforts towards characterizing molecular mechanisms that have a great potential for human reproductive medicine and could be used for a development of distinct diagnostic tools and potentially therapies for the majority of infertile patients.

• DFG Programme: Research Grants