What is the Molecular Link Between Infertility and Cancer?

Abstract

Female unexplained infertility is a multifactorial disorder, and its molecular underpinnings remain poorly understood. Approximately 15-20% of infertility cases are unexplained, posing a significant challenge for reproductive medicine. The endometrial epithelium's molecular network and signalling pathways play a crucial role in unexplained infertility, where the preservation of structural and functional integrity of maternal uterine tissue is essential for successful implantation and conception. The molecular environment within the uterus influences pregnancy establishment and development, with key components such as extracellular matrix (ECM) components, adhesion molecules, cytokines, and growth factors contributing to structural support and cellular processes. However, the intricate nature of these molecular networks necessitates further investigation. In our study, we employed proteome profiling techniques to analyse uterine tissue samples from women with unexplained infertility, aiming to identify potential alterations in specific proteins and pathways associated with infertility. Interestingly, emerging evidence suggests a molecular link between infertility and cancer in women. Infertility has been associated with an increased risk of certain cancers, including ovarian, endometrial, and breast cancer. Dysregulations in the uterine molecular environment may contribute to the development of cancer by promoting abnormal cell growth, impairing DNA repair mechanisms, and disrupting hormonal balance. Understanding the shared molecular mechanisms between infertility and cancer could provide valuable insights into both conditions. Using high-resolution two-dimensional gel electrophoresis and mass spectrometry, we identified twenty-four differentially expressed proteins, including ANKRD36, ZNF658B, MALRD1, and PRRC2A. Additionally, enrichment analysis revealed numerous pathways associated with infertility morbidity, highlighting their potential relevance to cancer development. These findings underscore the significance of investigating the molecular link between infertility and cancer, paving the way for future research aiming to unravel shared pathways and develop targeted interventions.