Adult Leydig cells develop from undifferentiated mesenchymal-like stem cells (stem Leydig cells, SLCs) present in the interstitial compartment of the early postnatal testis. Putative SLCs also have been identified in peritubular and perivascular locations of the adult testis. The latter cells, which normally are quiescent, are capable of regenerating new Leydig cells upon the loss of the adult cells. Recent studies have identified several protein markers to identify these cells, including nestin, PDGFRα, COUP-TFII, CD51 and CD90. We have shown that the proliferation of the SLCs is stimulated by DHH, FGF2, PDGFBB, activin and PDGFAA. Suppression of proliferation occurred with TGFβ, androgen and PKA signaling. The differentiation of the SLCs into testosterone-producing Leydig cells was found to be regulated positively by DHH (Desert hedgehog), lithium-induced signaling and activin; and negatively by TGFβ, PDGFBB, FGF2, Notch and Wnt signaling. DHH, by itself, was found to induce SLC differentiation into LH-responsive steroidogenic cells, suggesting that DHH plays a critical role in the commitment of SLC into the Leydig lineage. These studies, taken together, address the function and regulation of low turnover stem cells in a complex, adult organ, and also have potential application to the treatment of androgen deficiency.
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http://dx.doi.org/10.1016/j.mce.2016.10.010 | DOI Listing |
J Mol Histol
January 2025
Department of Histology and Embryology, Faculty of Veterinary Medicine, Sivas Cumhuriyet University, Sivas, Türkiye.
Although minimal increases in testicular temperature can compromise spermatogenesis and lead to fertility-related problems, the basic mechanism involved in germ cell destruction as a response to heat stress is still unclear. However, necroptosis is known to regulate a number of physiological and pathological events. This study investigated the role of RIPK1/RIPK3 and MLKL, the main regulators of necroptosis, against different heat stresses in testis tissue.
View Article and Find Full Text PDFCurr Issues Mol Biol
December 2024
College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China.
Spermatogenesis is an advanced biological process, relying on intricate interactions between somatic and germ cells in testes. Investigating various cell types is challenging because of cellular heterogeneity. Single-cell RNA sequencing (scRNA-seq) offers a method to analyze cellular heterogeneity.
View Article and Find Full Text PDFCells
January 2025
Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece.
Phosphodiesterases, particularly the type 5 isoform (PDE5), have gained recognition as pivotal regulators of male reproductive physiology, exerting significant influence on testicular function, sperm maturation, and overall fertility potential. Over the past several decades, investigations have expanded beyond the original therapeutic intent of PDE5 inhibitors for erectile dysfunction, exploring their broader reproductive implications. This narrative review integrates current evidence from in vitro studies, animal models, and clinical research to clarify the roles of PDEs in effecting the male reproductive tract, with an emphasis on the mechanistic pathways underlying cyclic nucleotide signaling, the cellular specificity of PDE isoform expression, and the effects of PDE5 inhibitors on Leydig and Sertoli cell functions.
View Article and Find Full Text PDFIran J Basic Med Sci
January 2025
Department of Animal Nutrition and Nutritional Disorders, Faculty of Veterinary Medicine, Ataturk University, Erzurum 25240, Turkey.
Objectives: This experiment was carried out to investigate the protective effects of curcumin (CUR) on testicular damage induced by the valproic acid (VPA) administration.
Materials And Methods: Male Wistar-Albino rats (n=28, 250-300 g) were randomly divided into four groups: Control (1 ml saline, oral), VPA (500 mg/kg, IP), CUR (200 mg/kg, oral), or VPA+CUR (500 mg/kg, VPA, IP plus 200 mg/kg CUR, oral). The treatments were applied for 14 days.
World J Mens Health
January 2025
TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Environmental endocrine disruptors, as exogenous chemicals that interfere with hormonal behavior, are known to cause testicular Leydig cell death and senescence. The incidence of diseases of the male reproductive system has been increasing over the past half-century. Genetic defects alone cannot explain the rapid increase in incidence, and there is growing evidence that environmental factors or lifestyle changes are responsible for the high incidence in recent years.
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