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Insulin-like peptide 3 (INSL3) is a small peptide hormone produced almost exclusively by testicular Leydig cells in males and thus serves as an essential biomarker of the maturation and functionality of these cells. Accumulated evidence suggests that INSL3 is a crucial factor affecting testicular descent during fetal development by regulating the growth of the gubernaculum. However, the physiological roles of INSL3 in adults remain unclear. Here, we reported that relaxin family peptide 2 (RXFP2), the receptor of INSL3, is expressed on macrophages, and treatment with INSL3 can promote M2 macrophage polarization via the Akt/mTOR/S6K and PKA/CREB pathways. In addition, INSL3 can inhibit macrophage phagocytosis and promote their migration via the Epac and PKA signaling pathways, respectively. These findings reveal a new role for INSL3 in regulating macrophage function and shed new light on our understanding of the role of INSL3 in adulthood.
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http://dx.doi.org/10.1016/j.intimp.2025.114540 | DOI Listing |
PLoS One
August 2025
Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México.
In mammals, insulin-like peptide 3 (INSL3) and its cognate receptor (RXFP2) are reported to be essential regulators of male reproductive physiology. It is also believed that INSL3/RXFP2 signaling has a role in female ovarian function and follicle development, although its exact mechanisms and functions are still being studied. This research aimed to explore the transcriptional landscape of INSL3/RXFP2 genes in adult hamsters.
View Article and Find Full Text PDFReprod Toxicol
July 2025
Biochemistry and Molecular Biology Department, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt. Electronic address:
Plasticizers are widely employed in various applications. Therefore, these products may have an impact on the biological systems of humans and other organisms. Thus, seeking a potent and eco-friendly protective agent becomes a great challenge.
View Article and Find Full Text PDFAndrology
July 2025
School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, UK.
Background: The constitutive Leydig cell hormone insulin-like peptide 3 (INSL3) is considered a good estimate of the adult Leydig cell functional capacity and appears to remain relatively consistent throughout adult male life, only gradually declining into old age. Importantly, in younger men it appears to predict hypogonadism and hence later health and morbidity.
Objectives: Here, we have used the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort of boys and young men to assess those factors during pregnancy, infancy, childhood, and adolescence, when the adult-type Leydig cell population is being established, which by association might influence the final circulating INSL3 concentration in young adulthood.
Medicine (Baltimore)
June 2025
Department of Gynaecology of Obstetrics, Medicana Atakoy Hospital, Istanbul, Turkiye.
Accurate assessment of ovarian reserve remains challenging in clinical practice, particularly when conventional markers like anti-müllerian hormone (AMH) and antral follicle count show inconsistent results. Despite widespread use, AMH has limitations in predicting reproductive lifespan and oocyte quality. This study evaluated 2 emerging biomarkers, insulin-like peptide-3 (INSL3) and tumor necrosis factor receptor 2 (TNFR2), for ovarian reserve assessment.
View Article and Find Full Text PDFCells
June 2025
Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece.
Male reproductive aging proceeds gradually and involves complex alterations across germ cells, somatic cells, and the testicular niche. Multi-omics analyses highlight shifts in spermatogonial stem cell dynamics, diminished sperm quantity and quality, and reconfigured support from Sertoli and Leydig cells. These somatic cells show numerical declines and exhibit senescence-associated changes that amplify inflammatory signals and compromise blood-testis barrier integrity.
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