The transcriptional regulation of NUPR1 expression by MYC is implicated in the regulation of ferroptosis in human spermatogonial stem cells.

Non-obstructive azoospermia (NOA) is a leading cause of male infertility, characterized by impaired spermatogenesis. Recent studies suggest that ferroptosis, an iron-dependent form of cell death, may contribute to testicular dysfunction, however, its role in NOA remains underexplored. In this study, we investigated the roles of NUPR1 and MYC in regulating ferroptosis in human spermatogonial stem cells (SSCs) and evaluated their potential as therapeutic targets for NOA.

G proteins of the G family expressed by POMC neurons regulate key metabolic functions.

Proopiomelanocortin (POMC) neurons play a key role in maintaining glucose and energy homeostasis. POMC neurons express many heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors that are linked to different functional classes of G proteins. The potential role of G in regulating the function of central POMC neurons remains unknown.

[Retracted] Genistein inhibits lung cancer cell stem-like characteristics by modulating MnSOD and FoxM1 expression.

[This retracts the article DOI: 10.3892/ol.2020.

Micro-proteomics reveals distinct protein profiles and SPARC/FGF2/CDH1 regulation of human Sertoli cells between Sertoli cell-only syndrome and normal men.

Sertoli cell-only syndrome (SCOS) is one of the most severe non-obstructive azoospermia (NOA) types, since only Sertoli cells with not any male germ cells exist with the seminiferous tubules. As such, it is of particular significance to elucidate molecular mechanisms underlying SCOS for improving the diagnosis and treatment strategies for this disease. Due to the difficulties in obtaining sufficient human testicular tissues and the limited availability of human cells, the traditional proteomics is inadequate for comparing the differences in large scale of protein expression patterns of human Sertoli cells between SCOS and normal men.

Essential Regulation of YAP1 in Fate Determinations of Spermatogonial Stem Cells and Male Fertility by Interacting with RAD21 and Targeting NEDD4 in Humans and Mice.

Spermatogenesis is a sophisticated biological process by which spermatogonial stem cells (SSCs) undergo self-renewal and differentiation into spermatozoa. Molecular mechanisms underlying fate determinations of human SSCs by key genes and signaling pathways remain elusive. Here, we report for the first time that Yes1-associated transcriptional regulator (YAP1) is required for fate determinations of SSCs and male fertility by interacting with RAD21 and targeting NEDD4 in humans and mice.

G-mediated signaling stimulates hepatic glucose production and has a major impact on whole body glucose homeostasis.

Altered hepatic glucose fluxes are critical during the pathogenesis of type 2 diabetes. G protein-coupled receptors represent important regulators of hepatic glucose production. Recent studies have shown that hepatocytes express GPCRs that can couple to G, a subfamily of heterotrimeric G proteins that has attracted relatively little attention in the past.

Activation of Gs signaling in mouse enteroendocrine K cells greatly improves obesity- and diabetes-related metabolic deficits.

Following a meal, glucagon-like peptide 1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP), the 2 major incretins promoting insulin release, are secreted from specialized enteroendocrine cells (L and K cells, respectively). Although GIP is the dominant incretin in humans, the detailed molecular mechanisms governing its release remain to be explored. GIP secretion is regulated by the activity of G protein-coupled receptors (GPCRs) expressed by K cells.

Establishment and Characterization of Testis Organoids with Proliferation and Differentiation of Spermatogonial Stem Cells into Spermatocytes and Spermatids.

Organoids play pivotal roles in uncovering the molecular mechanisms underlying organogenesis, intercellular communication, and high-throughput drug screening. Testicular organoids are essential for exploring the genetic and epigenetic regulation of spermatogenesis in vivo and the treatment of male infertility. However, the formation of testicular organoids with full spermatogenesis has not yet been achieved.

LncRNA ACVR2B-as1 interacts with ALDOA to regulate the self-renewal and apoptosis of human spermatogonial stem cells by controlling glycolysis activity.

Human spermatogonial stem cells (SSCs) have significant applications in reproductive medicine and regenerative medicine because of their great plasticity. Nevertheless, it remains unknown about the functions and mechanisms of long non-coding RNA (LncRNA) in regulating the fate determinations of human SSCs. Here we have demonstrated that LncRNA ACVR2B-as1 (activin A receptor type 2B antisense RNA 1) controls the self-renewal and apoptosis of human SSCs by interaction with ALDOA via glycolysis activity.

The functions and mechanisms of piRNAs in mediating mammalian spermatogenesis and their applications in reproductive medicine.

As the most abundant small RNAs, piwi-interacting RNAs (piRNAs) have been identified as a new class of non-coding RNAs with 24-32 nucleotides in length, and they are expressed at high levels in male germ cells. PiRNAs have been implicated in the regulation of several biological processes, including cell differentiation, development, and male reproduction. In this review, we focused on the functions and molecular mechanisms of piRNAs in controlling spermatogenesis, including genome stability, regulation of gene expression, and male germ cell development.

Intra-islet α-cell Gs signaling promotes glucagon release.

Glucagon, a hormone released from pancreatic α-cells, is critical for maintaining euglycemia and plays a key role in the pathophysiology of diabetes. To stimulate the development of new classes of therapeutic agents targeting glucagon release, key α-cell signaling pathways that regulate glucagon secretion need to be identified. Here, we focused on the potential importance of α-cell G signaling on modulating α-cell function.

WNT5A regulates the proliferation, apoptosis and stemness of human stem Leydig cells via the β-catenin signaling pathway.

Stem Leydig cells (SLCs) are essential for maintaining normal spermatogenesis as the significant component of testis microenvironment and gonadal aging. Although progress has been achieved in the regulation of male germ cells in mammals and humans, it remains unknown about the genes and signaling pathways of human SLCs. Here we have demonstrated, for the first time, that WNT5A (Wnt family member 5a) mediates the proliferation, apoptosis, and stemness of human SLCs, namely NGFR Leydig cells.

KLF2 controls proliferation and apoptosis of human spermatogonial stem cells via targeting GJA1.

Human spermatogonial stem cells (SSCs) are essential for spermatogenesis and male fertility. However, molecular mechanisms regulating fate determinations of human SSCs remain elusive. In this study, we revealed that KLF2 decreased the proliferation, DNA synthesis, and colonization of human SSCs as well as increased apoptosis of these cells.

ZBTB40 is a telomere-associated protein and protects telomeres in human ALT cells.

Alternative lengthening of telomeres (ALTs) mechanism is activated in some somatic, germ cells, and human cancer cells. However, the key regulators and mechanisms of the ALT pathway remain elusive. Here we demonstrated that ZBTB40 is a novel telomere-associated protein and binds to telomeric dsDNA through its N-terminal BTB (BR-C, ttk and bab) or POZ (Pox virus and Zinc finger) domain in ALT cells.

OIP5 Interacts with NCK2 to Mediate Human Spermatogonial Stem Cell Self-Renewal and Apoptosis through Cell Cyclins and Cycle Progression and Its Abnormality Is Correlated with Male Infertility.

Spermatogonial stem cells (SSCs) have important applications in both reproduction and regenerative medicine. Nevertheless, specific genes and signaling transduction pathways in mediating fate decisions of human SSCs remain elusive. Here, we have demonstrated for the first time that OIP5 (Opa interacting protein 5) controlled the self-renewal and apoptosis of human SSCs.

Deficiency Leads to Morphological and Phenotypic Abnormalities of Spermatocytes and Spermatozoa and Causes Male Infertility.

Studies on the gene regulation of spermatogenesis are of unusual significance for maintaining male reproduction and treating male infertility. Here, we have demonstrated, for the first time, that a loss of ZBTB40 function leads to abnormalities in the morphological and phenotypic characteristics of mouse spermatocytes and spermatids as well as male infertility. We revealed that Zbtb40 was expressed in spermatocytes of mouse testes, and it was co-localized with γH2AX in mouse secondary spermatocytes.

MAP4K4/JNK Signaling Pathway Stimulates Proliferation and Suppresses Apoptosis of Human Spermatogonial Stem Cells and Lower Level of MAP4K4 Is Associated with Male Infertility.

Spermatogonial stem cells (SSCs) serve as a foundation for spermatogenesis and they are essential for male fertility. The fate of SSC is determined by genetic and epigenetic regulatory networks. Many molecules that regulate SSC fate determinations have been identified in mice.

RNF144B stimulates the proliferation and inhibits the apoptosis of human spermatogonial stem cells via the FCER2/NOTCH2/HES1 pathway and its abnormality is associated with azoospermia.

Studies on gene regulation and signaling transduction pathways of human spermatogonial stem cells (SSCs) are of the utmost significance for unveiling molecular mechanisms underlying human spermatogenesis and gene therapy of male infertility. We have demonstrated, for the first time, that RNF144B stimulated cell proliferation and inhibited the apoptosis of human SSCs. The target of RNF144B was identified as FCER2 by RNA sequencing.

Generation of male germ cells from the stem cells.

Infertility has become a serious disease since it affects 10%-15% of couples worldwide, and male infertility contributes to about 50% of the cases. Notably, a significant decrease occurs in the newborn population by 7.82 million in 2020 compared to 2016 in China.

Adipocyte G signaling is a regulator of glucose and lipid homeostasis in mice.

Obesity is the major driver of the global epidemic in type 2 diabetes (T2D). In individuals with obesity, impaired insulin action leads to increased lipolysis in adipocytes, resulting in elevated plasma free fatty acid (FFA) levels that promote peripheral insulin resistance, a hallmark of T2D. Here we show, by using a combined genetic/biochemical/pharmacologic approach, that increased adipocyte lipolysis can be prevented by selective activation of adipocyte G signaling in vitro and in vivo (in mice).