Glutathione S-transferases (GSTs) are a family of detoxification isoenzymes present in different tissues including the testis and that conjugate many toxic substrates to glutathione. Among these substrates are carcinogens, mutagens and products of oxidative processes. In the present report we show that GSTalpha is expressed in somatic testicular Leydig cells and Sertoli cells. GSTalpha expression in Sertoli cells is under the hormonal control of FSH, testosterone, and estradiol. In Leydig cells, immunoreactive GSTalpha was present at the neonatal, pubertal, and adult periods. In Sertoli cells, GSTalpha was predominant in pubertal and adult testes (but not in neonatal testes), suggesting that its expression is controlled by gonadotropins. The regulatory action and the mechanisms of action of FSH and testosterone on GSTalpha mRNA and protein levels were studied by using a model of primary cultures of porcine testicular Sertoli cells. FSH increased GSTalpha mRNA levels in a dose-dependent manner (ED50 = 18.5 nm/ml) with a maximal effect observed after 48 h of exposure (a 3-fold increase; P < 0.001). In addition, FSH increased GSTalpha protein, which was detected as a doublet of 28 kDa. Treatment with testosterone enhanced GSTalpha mRNA levels in a dose-dependent (ED50 = 1.4 ng/ml) and time-dependent manner with a maximal effect delayed at 8 h of exposure (a 2-fold increase; P < 0.001). Similarly, Sertoli cell treatment with testosterone metabolites, dihydrotestosterone (DHT) and estradiol, led to an increase in GSTalpha mRNA levels. Because stimulatory effects of FSH and androgens were also observed on GSTalpha protein, we therefore had to determine whether the different hormones were affecting GSTalpha gene transcriptional activity, or GSTalpha mRNA stability, or both. FSH and 8-Br-cAMP (but not testosterone) increased the stability of GSTalpha mRNA. The effects of FSH and testosterone on GSTalpha protein were additive, confirming that both hormones act through distinct mechanisms on the expression of the enzyme. Taken together, the present observations indicate that Sertoli cell GSTalpha is targeted by FSH, testosterone, and its metabolites, and they reinforce the concept that Sertoli cells exert a protective role and are under endocrine control to ward against toxic agents in the context of Sertoli-germ cell interactions during spermatogenesis.
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http://dx.doi.org/10.1095/biolreprod66.6.1734 | DOI Listing |
BMC Med Genomics
January 2025
Department of Surgery, Faculty of General of Medicine, Koya University, Koya, Kurdistan Region - F.R., KOY45, Iraq.
Background: During mammalian spermatogenesis, the cytoskeleton system plays a significant role in morphological changes. Male infertility such as non-obstructive azoospermia (NOA) might be explained by studies of the cytoskeletal system during spermatogenesis.
Methods: The cytoskeleton, scaffold, and actin-binding genes were analyzed by microarray and bioinformatics (771 spermatogenic cellsgenes and 774 Sertoli cell genes).
Hum Reprod Update
January 2025
Amsterdam UMC, Location Vrije Universiteit Amsterdam, Centre of Expertise on Gender Dysphoria, Amsterdam, The Netherlands.
Background: Transgender and gender diverse (TGD) people seek gender-affirming care at any age to manage gender identities or expressions that differ from their birth gender. Gender-affirming hormone treatment (GAHT) and gender-affirming surgery may alter reproductive function and/or anatomy, limiting future reproductive options to varying degrees, if individuals desire to either give birth or become a biological parent.
Objective And Rationale: TGD people increasingly pursue help for their reproductive questions, including fertility, fertility preservation, active desire for children, and future options.
Curr 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 PDFZool Res
January 2025
Department of Reproductive Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210000, China.
Increasing evidence implicates disruptions in testicular fatty acid metabolism as a contributing factor in non-obstructive azoospermia (NOA), a severe form of male infertility. However, the precise mechanisms linking fatty acid metabolism to NOA pathogenesis have not yet been fully elucidated. Multi-omics analyses, including microarray analysis, single-cell RNA sequencing (scRNA-seq), and metabolomics, were utilized to investigate disruptions in fatty acid metabolism associated with NOA using data from public databases.
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