PTN from Leydig cells activates SDC2 and modulates human spermatogonial stem cell proliferation and survival via GFRA1.

BACKGROUND: Spermatogonial stem cells (SSCs) are essential for the maintenance and initiation of male spermatogenesis. Despite the advances in understanding SSC biology in mouse models, the mechanisms underlying human SSC development remain elusive. RESULTS: Here, we analyzed the signaling pathways involved in SSC regulation by testicular somatic cells using single-cell sequencing data (GEO datasets: GSE149512 and GSE112013) and identified that Leydig cells communicate with SSCs through pleiotrophin (PTN) and its receptor syndecan-2 (SDC2). Immunofluorescence, STRING prediction, and protein immunoprecipitation assays confirmed the interaction between PTN and SDC2 in spermatogonia, but their co-localization was observed only in approximately 50% of the cells. The knockdown of SDC2 in human SSC lines impaired cell proliferation, DNA synthesis, and the expression of PLZF, a key marker for SSC self-renewal. Transcriptome analysis revealed that SDC2 knockdown downregulated the expression of GFRA1, a crucial factor for SSC proliferation and self-renewal, and inhibited the HIF-1 signaling pathway. Exogenous PTN rescued the proliferation and GFRA1 expression in SDC2 knockdown SSC lines. In addition, we found downregulation of PTN and SDC2 as well as altered localization in non-obstructive azoospermia (NOA) patients, suggesting that downregulation of PTN and SDC2 may be associated with impaired spermatogenesis. CONCLUSIONS: Our results uncover a novel mechanism of human SSC regulation by the testicular microenvironment and suggest a potential therapeutic target for male infertility.

A rare case of meningitis and septicemia caused by Streptococcus suis in a woman without a history of live pig contact or eating raw pork.

Streptococcus suis (S. suis) is a zoonotic pathogen that primarily inhabits the upper respiratory tract of pigs. Therefore, pigs that carry these pathogens are the major source of infection. Most patients are infected through contact with live pigs or unprocessed pork products and eating uncooked pork. S. Suis mainly causes sepsis and meningitis. The disease has an insidious onset and rapid progress. The patient becomes critically ill and the mortality is high. In this case report, we described a rare case of S. suis isolated from a middle-aged woman in Jinhua City, Zhejiang Province, China, who did not have any contact with live pigs and had not eaten uncooked pork. S. Suis was isolated from both the patient's blood and cerebrospinal fluid samples.