Sertoli Cell-Only Syndrome Human Transcriptome Profiling Study

Sertoli cell-only syndrome is severe form of human male infertility in which most seminiferous tubules appear to lack all spermatogenic cells, including spermatogonial stem cells (SSCs). However, a few small tubule segments of some patients have active spermatogenesis and, thus, functional stem cell niches and SSCs. Normally SSCs replicate, migrate and refill adjacent empty niches, but this does not appear to occur in SCO syndrome. We hypothesized that this failure occurs because most niches are dysfunctional. As Sertoli cells are essential to formation of these niches, we used RNAseq to compare the transcriptomes of human testes with qualitatively normal (complete) spermatogenesis (n=4) with the transcriptomes of human testes with SCO syndrome (n=7). We then focused our analysis on the expression of transcripts that bioinformatic analyses identified as Sertoli cell signature transcripts. Results show that Sertoli cells in SCO testes express abnormally low levels of GDNF, FGF8 and BMP4, all of which are important regulators of mouse SSCs and/or progenitor spermatogonia. Sertoli cells in SCO testes express significantly reduced levels of transcripts for proteins that polarize the Sertoli cell plasma membrane and regulate the trafficking of cell adhesion and gap junction proteins in and out of that plasma membrane.]]> Testis biopsies were collected as part of standard care of infertile men undergoing retrieval of testicular sperm by micro-testicular sperm extraction. A fragment of each biopsy was deposited in the Weill Cornell Department of Urology Testicular Tissue Repository; the other fragment was used for histological evaluation of the testis. Collections occurred in 2013. RNAseq was performed on 11 biopsies. Four testes exhibited complete spermatogenesis. Seven testes were diagnosed with Sertoli cell-only syndrome. The samples we analyzed were selected in order to insure similar ages, weights and heights of the patients for the patients in the two groups.]]> This study is one of a number conducted by the Department of Urology at Weill Cornell Medical College to identify molecular bases of testicular failure. 11 testes biopsies were collected and sequenced in 2013. The analysis and interpretation of data were conducted in collaboration with the Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health. This collaboration was funded in part by grants from the Eunice Kennedy Shriver National Institute for Child Health and Human Development, National Centers for Translational Research in Reproduction and Infertility Program (NCTRI).]]>