The Role of Lipocalin 2 in the Reproductive System - Insights on Expression and Function in the Testis

• Applicant: Dr. Sarah Katharina Schröder-Lange
• Subject Area: Reproductive Medicine, Urology ; Biochemistry ; Cell Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 572481158

Lipocalin 2 (LCN2), originally isolated from neutrophils and described as a transporter of small hydrophobic molecules, has been intensively studied in liver-related pathologies. Additionally, there is high expression of LCN2 in various reproductive cancers which classifies it as a valuable biomarker and a potential therapeutic target. To fully comprehend LCN2 in a pathophysiological context, it is essential to study its physiological functions. However, there is limited data on the physiological expression and function of LCN2 in reproductive systems. LCN2 expression can be regulated by steroid hormones, particularly by estrogens as the LCN2 promoter contains an estrogen responsive element. Recently, it has been shown that depletion of estrogen receptor alpha, a major component in estrogen signaling, results in significantly increased LCN2 expression in murine ovaries and testes. Moreover, there is evidence linking LCN2 to fertility, as global depletion of LCN2 negatively impacts reproductive capacity in mice. Conversely, induced infertility models in male mice have led to increased testicular LCN2 expression. However, a comprehensive understanding of its physiological role in the reproductive system is still lacking. The aim of this project is to gain a thorough understanding of the role of LCN2 in male reproductive system. Initially, we will decipher the precise expression patterns of LCN2 in the male reproductive tissue under physiological conditions, focusing on the testicular system. Additionally, tissues from Lcn2-deficient mice will be utilized to unravel the functions of LCN2 by assessing histology, spermatogenesis and steroidogenesis. In vitro, we will study how LCN2 elicits its functions by stimulating appropriate primary testicular cells and cell lines with exogenous LCN2 to characterize the signaling pathways in which LCN2 is involved. Lastly, LCN2 expression will be investigated in the diseased human testis to assess whether the mouse data can be extended to human physiology. The overall aim of this project is to gain new insights into the function and regulation of LCN2 in the testis. The project will enhance our knowledge of LCN2 and its role in the male reproductive tract, providing a foundation for better understanding the transition to pathophysiological diseases.

• DFG Programme: Research Grants