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International Journal of Gynecological... Dec 2023
PubMed: 38088150
DOI: 10.1136/ijgc-2023-004321 -
Autophagy Dec 2023Reproduction is characterized by a series of massive renovations at molecular, cellular, and tissue levels. Recent studies have strongly tended to reveal the involvement... (Review)
Review
Reproduction is characterized by a series of massive renovations at molecular, cellular, and tissue levels. Recent studies have strongly tended to reveal the involvement of basic molecular pathways such as autophagy, a highly conserved eukaryotic cellular recycling, during reproductive processes. This review comprehensively describes the current knowledge, updated to September 2022, of autophagy contribution during reproductive processes in males including spermatogenesis, sperm motility and viability, and male sex hormones and females including germ cells and oocytes viability, ovulation, implantation, fertilization, and female sex hormones. Furthermore, the consequences of disruption in autophagic flux on the reproductive disorders including oligospermia, azoospermia, asthenozoospermia, teratozoospermia, globozoospermia, premature ovarian insufficiency, polycystic ovarian syndrome, endometriosis, and other disorders related to infertility are discussed as well. AKT/protein kinase B: AKT serine/threonine kinase; AMPK: AMP-activated protein kinase; ATG: autophagy related; E estrogen; EDs: endocrine disruptors; ER: endoplasmic reticulum; FSH: follicle stimulating hormone; FOX: forkhead box; GCs: granulosa cells; HIF: hypoxia inducible factor; IVF: in vitro fertilization; IVM: in vitro maturation; LCs: Leydig cells; LDs: lipid droplets; LH: luteinizing hormone; LRWD1: leucine rich repeats and WD repeat domain containing 1; MAP1LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MTOR: mechanistic target of rapamycin kinase; NFKB/NF-kB: nuclear factor kappa B; P: progesterone; PCOS: polycystic ovarian syndrome; PDLIM1: PDZ and LIM domain 1; PI3K: phosphoinositide 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; PtdIns3K: class III phosphatidylinositol 3-kinase; POI: premature ovarian insufficiency; ROS: reactive oxygen species; SCs: Sertoli cells; SQSTM1/p62: sequestosome 1; TSGA10: testis specific 10; TST: testosterone; VCP: vasolin containing protein.
Topics: Humans; Male; Female; Proto-Oncogene Proteins c-akt; Autophagy; Phosphatidylinositol 3-Kinases; Polycystic Ovary Syndrome; Reproducibility of Results; Sperm Motility; Gonadal Steroid Hormones; Cytoskeletal Proteins
PubMed: 37505071
DOI: 10.1080/15548627.2023.2238577 -
Frontiers in Endocrinology 2024Cryptorchidism is the condition in which one or both testes have not descended adequately into the scrotum. The congenital form of cryptorchidism is one of the most... (Review)
Review
Cryptorchidism is the condition in which one or both testes have not descended adequately into the scrotum. The congenital form of cryptorchidism is one of the most prevalent urogenital anomalies in male newborns. In the acquired form of cryptorchidism, the testis that was previously descended normally is no longer located in the scrotum. Cryptorchidism is associated with an increased risk of infertility and testicular germ cell tumors. However, data on pubertal progression are less well-established because of the limited number of studies. Here, we aim to review the currently available data on pubertal development in boys with a history of non-syndromic cryptorchidism-both congenital and acquired cryptorchidism. The review is focused on the timing of puberty, physical changes, testicular growth, and endocrine development during puberty. The available evidence demonstrated that the timing of the onset of puberty in boys with a history of congenital cryptorchidism does not differ from that of non-cryptorchid boys. Hypothalamic-pituitary-gonadal hormone measurements showed an impaired function or fewer Sertoli cells and/or germ cells among boys with a history of cryptorchidism, particularly with a history of bilateral cryptorchidism treated with orchiopexy. Leydig cell function is generally not affected in boys with a history of cryptorchidism. Data on pubertal development among boys with acquired cryptorchidism are lacking; therefore, more research is needed to investigate pubertal progression among such boys.
Topics: Infant, Newborn; Humans; Male; Cryptorchidism; Testicular Neoplasms; Leydig Cells; Puberty
PubMed: 38532895
DOI: 10.3389/fendo.2024.1347435 -
Science (New York, N.Y.) Nov 2023Sex determination in mammals depends on the differentiation of the supporting lineage of the gonads into Sertoli or pregranulosa cells that govern testis and ovary...
Sex determination in mammals depends on the differentiation of the supporting lineage of the gonads into Sertoli or pregranulosa cells that govern testis and ovary development, respectively. Although the Y-linked testis-determining gene has been identified, the ovarian-determining factor remains unknown. In this study, we identified -KTS, a major, alternatively spliced isoform of the Wilms tumor suppressor WT1, as a key determinant of female sex determination. Loss of - variants blocked gonadal differentiation in mice, whereas increased expression, as found in Frasier syndrome, induced precocious differentiation of ovaries independently of their genetic sex. In XY embryos, this antagonized expression, resulting in male-to-female sex reversal. Our results identify -KTS as an ovarian-determining factor and demonstrate that its time of activation is critical in gonadal sex differentiation.
Topics: Animals; Female; Male; Mice; Ovary; Sex Determination Processes; Sex-Determining Region Y Protein; Testis; WT1 Proteins; Protein Isoforms
PubMed: 37917714
DOI: 10.1126/science.add8831 -
Reproductive Sciences (Thousand Oaks,... Apr 2024Spermatogenesis is a complex process of germ cell division and differentiation that involves extensive cross-talk between the developing germ cells and the somatic... (Review)
Review
Spermatogenesis is a complex process of germ cell division and differentiation that involves extensive cross-talk between the developing germ cells and the somatic testicular cells. Defective endocrine signaling and/or intrinsic defects within the testes can adversely affect spermatogenic progression, leading to subfertility/infertility. In recent years, male infertility has been recognized as a global public health concern, and research over the last few decades has elucidated the complex etiology of male infertility. Congenital reproductive abnormalities, genetic mutations, and endocrine/metabolic dysfunction have been demonstrated to be involved in infertility/subfertility in males. Furthermore, acquired factors like exposure to environmental toxicants and lifestyle-related disorders such as illicit use of psychoactive drugs have been shown to adversely affect spermatogenesis. Despite the large body of available scientific literature on the etiology of male infertility, a substantial proportion of infertility cases are idiopathic in nature, with no known cause. The inability to treat such idiopathic cases stems from poor knowledge about the complex regulation of spermatogenesis. Emerging scientific evidence indicates that defective functioning of testicular Sertoli cells (Sc) may be an underlying cause of infertility/subfertility in males. Sc plays an indispensable role in regulating spermatogenesis, and impaired functional maturation of Sc has been shown to affect fertility in animal models as well as humans, suggesting abnormal Sc as a potential underlying cause of reproductive insufficiency/failure in such cases of unexplained infertility. This review summarizes the major causes of infertility/subfertility in males, with an emphasis on infertility due to dysregulated Sc function.
Topics: Animals; Male; Humans; Testis; Infertility, Male; Sertoli Cells; Spermatogenesis; Fertility
PubMed: 38036863
DOI: 10.1007/s43032-023-01401-x -
Scientific Reports Jul 2023Sertoli cell-only syndrome (SCOS), a severe testicular spermatogenic failure, is characterized by total absence of male germ cells. To better expand the understanding of...
Sertoli cell-only syndrome (SCOS), a severe testicular spermatogenic failure, is characterized by total absence of male germ cells. To better expand the understanding of the potential molecular mechanisms of SCOS, we used microarray datasets from the Gene Expression Omnibus (GEO) and ArrayExpress databases to determine the differentially expressed genes (DEGs). In addition, functional enrichment analysis including the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed. Protein-protein interaction (PPI) networks, modules, and miRNA-mRNA regulatory networks were constructed and analyzed and the validation of hub genes was performed. A total of 601 shared DEGs were identified, including 416 down-regulated and 185 up-regulated genes. The findings of the enrichment analysis indicated that the shared DEGs were mostly enriched in sexual reproduction, reproductive process, male gamete generation, immune response, and immunity-related pathways. In addition, six hub genes (CCNA2, CCNB2, TOP2A, CDC20, BUB1, and BUB1B) were selected from the PPI network by using the cytoHubba and MCODE plug-ins. The expression levels of the hub genes were significantly decreased in patients with SCOS compared to that in normal spermatogenesis controls as indicated by the microarray data, single-cell transcriptomic data, and clinical sample levels. Furthermore, the potential miRNAs were predicted via the miRNA-mRNA network construction. These hub genes and miRNAs can be used as potential biomarkers that may be related to SCOS. However, it has not been proven that the differential expression of these biomarkers is the molecular pathogenesis mechanisms of SCOS. Our findings suggest that these biomarkers can be serve as clinical tool for diagnosis targets and may have some impact on the spermatogenesis of SCOS from a testicular germ cell perspective.
Topics: Humans; Male; Sertoli Cell-Only Syndrome; Gene Regulatory Networks; Gene Expression Profiling; MicroRNAs; Biomarkers, Tumor; Computational Biology; RNA, Messenger; Gene Expression Regulation, Neoplastic
PubMed: 37500704
DOI: 10.1038/s41598-023-38947-4 -
The Science of the Total Environment Dec 2023Cypermethrin is a pyrethroid insecticide that is used to control insects and protect crops. However, pesticide residues and their possible toxicity to non-target animals...
Cypermethrin is a pyrethroid insecticide that is used to control insects and protect crops. However, pesticide residues and their possible toxicity to non-target animals such as mammals are concerning. Although cypermethrin reduces testosterone levels, the molecular mechanisms involved, particularly those regarding endoplasmic reticulum (ER) stress and autophagy regulation, have not yet been fully elucidated. In this study, we demonstrated testicular toxicity of cypermethrin in mouse Leydig (TM3) and Sertoli (TM4) cells. Cypermethrin suppresses TM3 and TM4 cell proliferation and induces apoptosis. Moreover, it interrupted calcium homeostasis in intracellular organelles and dissipated mitochondrial membrane polarization in mouse testicular cells. Moreover, we verified the accumulation of Sqstm1/p62 protein in the mitochondria of cypermethrin-treated TM3 and TM4 cells. Furthermore, we confirmed that cypermethrin activated autophagy and the ER stress pathway in a time-dependent manner in both cell types. Finally, we determined that cypermethrin downregulated testicular function-related genes, steroidogenesis, and spermatogenesis in mouse testis cells. Therefore, we conclude that cypermethrin regulates autophagy and ER stress, leading to testicular dysfunction.
Topics: Male; Animals; Mice; Testis; Pyrethrins; Endoplasmic Reticulum Stress; Autophagy; Apoptosis; Mammals
PubMed: 37567297
DOI: 10.1016/j.scitotenv.2023.166167