Sperm develop from puberty in the seminiferous tubules, inside the blood-testis barrier to prevent their recognition as "non-self" by the immune system, and it is widely assumed that human sperm-specific proteins cannot access the circulatory or immune systems. Sperm-specific proteins aberrantly expressed in cancer, known as cancer-testis antigens (CTAs), are often pursued as cancer biomarkers and therapeutic targets based on the assumption they are neoantigens absent from the circulation in healthy men. Here, we identify a wide range of germ cell-derived and sperm-specific proteins, including multiple CTAs, that are selectively deposited by the Sertoli cells of the adult mouse and human seminiferous tubules into testicular interstitial fluid (TIF) that is "outside" the blood-testis barrier. From TIF, the proteins can access the circulatory- and immune systems. Disruption of spermatogenesis decreases the abundance of these proteins in mouse TIF, and a sperm-specific CTA is significantly decreased in TIF from infertile men, suggesting that exposure of certain CTAs to the immune system could depend on fertility status. The results provide a rationale for the development of blood-based tests useful in the management of male infertility and indicate CTA candidates for cancer immunotherapy and biomarker development that could show sex-specific and male-fertility-related responses.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898903 | PMC |
| http://dx.doi.org/10.1096/fj.202002484R | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Antagonistic interaction between miR-143 and KRAS gene regulating male mouse germ cell apoptosis.
Theriogenology
January 2025
College of Agriculture and Bioengineering, Heze University, Heze, 274000, China. Electronic address:
Precisely regulated spermatocyte growth, differentiation, and apoptosis are crucial for sustainable male fertility. miR-143 has been demonstrated to regulate gene expression and cell apoptosis in various human cancers. However, the function of mmu-mir-143 (miR-143) in mammalian testes and its underlying mechanism remains unexplored.
View Article and Find Full Text PDFImpact of leachate from boiled-water-treated plastic products on male reproductive health: Insights from transcriptomic and metabolomic profiling.
Ecotoxicol Environ Saf
January 2025
Department of Urology & Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China. Electronic address:
Given the extensive use of plastic materials in modern society, there is an escalating concern about the potential risks associated with exposure to plastic products. This study investigated the impact of plastic leachates from boiled-water-treated cups, including polypropylene (PP), high-density polyethylene (HDPE), low-density polyethylene (LDPE), polystyrene (PS), and polyethylene terephthalate (PET), on male reproductive health. Experimental mice were administered daily doses of the plastic leachates for 180 consecutive days.
View Article and Find Full Text PDFUtilization of the QuPath open-source software platform for analysis of mammalian spermatogenesis.
Biol Reprod
January 2025
Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, NC USA.
The adult mammalian testis is filled with seminiferous tubules, which contain somatic Sertoli cells along with germ cells undergoing all phases of spermatogenesis. During spermatogenesis in postnatal mice, male germ cells undergo at least 17 different nomenclature changes as they proceed through mitosis as spermatogonia (=8), meiosis as spermatocytes (=6), and spermiogenesis as spermatids (=3) [1-6]. Adding to this complexity, combinations of germ cells at each of these stages of development are clumped together along the length of the seminiferous tubules.
View Article and Find Full Text PDFEffect of vortioxetine and fluoxetine on immunohistochemical expression of Caspase-8, RANKL, and IL-6 in testicular tissue in an experimental depression model.
Biotech Histochem
January 2025
Faculty of Medicine, Department of Medical Pathology, Sivas Cumhuriyet University, Sivas, Turkey.
The main symptoms of depression, a chronic mental illness, include sadness, low self-esteem, and a diminished sense of enjoyment in life. Many factors have been suggested to be associated with depression, one of which is low testosterone in men. The serotonin reuptake inhibitor fluoxetine (FLU), used to treat depression, has been reported to potentially have detrimental effects on spermatogenesis in rats after long-term use.
View Article and Find Full Text PDFInvestigating intrauterine exposure to methamphetamine on serine-threonine kinase pathway in male rat testis.
Cell Mol Biol (Noisy-le-grand)
January 2025
Department of Physiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Article Synopsis
- Intrauterine exposure to methamphetamine (METH) during pregnancy negatively impacts testicular development in offspring, leading to apoptosis in spermatids.
- Research focused on proteins involved in sperm growth pathways, particularly TSSK and RIPK2, showing significant changes in their expression levels due to METH exposure.
- Findings indicated that METH exposure resulted in decreased TSSK expression, increased RIPK2 expression, thinner germ layers, more inflammatory cells, and a reduction in the thickness of seminiferous tubules in rat testes.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!