The role of the mammalian Y chromosome in spermatogenesis

Development ◽  
1987 ◽  
Vol 101 (Supplement) ◽  
pp. 133-141
Author(s):  
Paul S. Burgoyne
Keyword(s):  
Y Chromosome ◽  
Germ Cells ◽  
Germ Line ◽  
Fetal Life ◽  
Chromosomal Gene ◽  
Male Germ Line ◽  
Germ Cell Differentiation ◽  
Sperm Abnormalities ◽  
Male Phenotype

All aspects of the mammalian male phenotype are due either directly or indirectly to Y-chromosome activity. This review summarizes what is known of the role of the Y in male germ cell differentiation in the mouse. The initial diversion of germ cells to the male pathway in fetal life (that is the formation of amitotic T1-prospermatogonia rather than meiotic oocytes) is an indirect effect of the Y: the Y-chromosomal testis determining gene (Tdy) acts to create a testis and the testicular environment causes the germ cells to follow the male pathway. XX and XO germ cells can therefore form T1-prospermatogonia, but the extra X of XX prospermatogonia in some way causes their death perinatally. The first direct effect of the Y in the germ line occurs at the initiation of the spermatogenic cycles (approx. 1 week after birth) when a Y-chromosomal gene (Spy) is needed for normal spermatogonial survival and progression to meiosis. Spy is present in the Y-derived Sxr fragment so XOSxr germ cells enter meiosis normally. An Sxr derivative, Sxr′, which has lost the capacity to produce H-Y antigen, has also lost the Spy function, raising the possibility that H-Y antigen is the mediator of Spy activity. The Y is next required in the male germ line during meiotic prophase, when it provides a pairing partner for the X chromosome. If the X (or, indeed, the Y when present) remains unpaired, there are severe spermatogenic losses and the second meiotic division is frequently omitted, leading to the formation of diploid spermatids. Spermatogenesis in XOSxr males is affected in this way and the few sperm produced are morphologically abnormal. These sperm abnormalities could also be a consequence of the X univalence, but there is some evidence suggesting that there is another gene on the Y, lacking in Sxr, which is involved in sperm morphogenesis.

Dual role of Ovol2 on the germ cell lineage segregation during gastrulation in mouse embryogenesis

Development ◽  
2022 ◽  
Author(s):  
Yuki Naitou ◽  
Go Nagamatsu ◽  
Nobuhiko Hamazaki ◽  
Kenjiro Shirane ◽  
Masafumi Hayashi ◽  
...  
Keyword(s):  
Germ Cells ◽  
Splice Variant ◽  
Epithelial To Mesenchymal Transition ◽  
Functional Relationship ◽  
Germ Line ◽  
Primordial Germ Cells ◽  
Cell Lineage ◽  
Animal Kingdom ◽  
Mesenchymal Transition

In mammals, primordial germ cells (PGCs), the origin of the germ line, are specified from the epiblast at the posterior region where gastrulation simultaneously occurs, yet the functional relationship between PGC specification and gastrulation remains unclear. Here, we show that Ovol2, a transcription factor conserved across the animal kingdom, balances these major developmental processes by repressing the epithelial-to-mesenchymal transition (EMT) driving gastrulation and the upregulation of genes associated with PGC specification. Ovol2a, a splice variant encoding a repressor domain, directly regulates EMT-related genes and consequently induces re-acquisition of potential pluripotency during PGC specification, whereas Ovol2b, another splice variant missing the repressor domain, directly upregulates genes associated with PGC specification. Taken together, these results elucidate the molecular mechanism underlying allocation of the germ line among epiblast cells differentiating into somatic cells through gastrulation.

Developmental expression of c-kit, a proto-oncogene encoded by the W locus

Development ◽  
1990 ◽  
Vol 109 (4) ◽  
pp. 911-923 ◽  
Author(s):  
A. Orr-Urtreger ◽  
A. Avivi ◽  
Y. Zimmer ◽  
D. Givol ◽  
Y. Yarden ◽  
...  
Keyword(s):  
Germ Cells ◽  
Receptor Tyrosine Kinase ◽  
Germ Line ◽  
Primordial Germ Cells ◽  
Mouse Embryos ◽  
Developmental Expression ◽  
Male Germ Line ◽  
Polypeptide Growth Factors ◽  
Adult Ovary

Developmental expression of the c-kit proto-oncogene, a receptor tyrosine kinase encoded by the W locus, was investigated by in situ hybridization in normal mouse embryos. Early after implantation transcripts were detectable only in the maternal placenta (6 1/2-7 1/2 days p.c.). Subsequently (8 1/2 days p.c.) numerous ectodermal (neural tube, sensory placodes) and endodermal (embryonic gut) derivatives expressed c-kit. Later transcripts were detected also in the blood islands of the yolk sac and in the embryonic liver, the main sites of embryonic hemopoiesis. Around midgestation, transcripts accumulated in the branchial pouches and also in primordial germ cells of the genital ridges. This complex pattern of expression remained characteristic also later in gestation, when c-kit was expressed in highly differentiated structures of the craniofacial area, in presumptive melanoblasts and in the CNS. In the adult ovary, maternal c-kit transcripts were detected. They were present in the oocytes of both immature and mature ovarian follicles, but not in the male germ line, where c-kit expression may be down regulated. Thus, c-kit activity is complex and appears in multiple tissues including those that also display defects in mutations at the W locus where c-kit is encoded. Correlation between W phenotypes and c-kit expression, as well as the regulation of the complex and multiple expression of polypeptide growth factors and receptors, is discussed.

DNA methyltransferase 1 (Dnmt1) mutation affects Snrpn imprinting in the mouse male germ line

Genome ◽  
2012 ◽  
Vol 55 (09) ◽  
pp. 673-682 ◽  
Author(s):  
Aabida Saferali ◽  
Sanny Moussette ◽  
Donovan Chan ◽  
Jacquetta Trasler ◽  
Taiping Chen ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Germ Line ◽  
Dna Methyltransferases ◽  
Dna Methyltransferase 1 ◽  
Loss Of Function ◽  
Male Germ Line ◽  
Epigenetic Remodeling ◽  
Genomic Imprints ◽  
Mature Spermatozoa

DNA methylation and DNA methyltransferases are essential for spermatogenesis. Mutations in the DNA methyltransferase Dnmt1 gene exert a paternal effect on epigenetic states and phenotypes of offspring, suggesting that DNMT1 is important for the epigenetic remodeling of the genome that takes place during spermatogenesis. However, the specific role of DNMT1 in spermatogenesis and the establishment of genomic imprints in the male germ line remains elusive. To further characterize the effect of DNMT1 deficiency on the resetting of methylation imprints during spermatogenesis, we analyzed the methylation profiles of imprinted regions in the spermatozoa of mice that were heterozygous for a Dnmt1 loss-of-function mutation. The mutation did not affect the H19 or IG differentially methylated regions (DMRs) that are usually highly methylated but led to a partial hypermethylation of the Snrpn DMR, a region that should normally be unmethylated in mature spermatozoa. This defect does not appear in mouse models with mutations in Dnmt3a and Mthfr genes and, therefore, it is specific for the Dnmt1 gene and is suggestive of a role of DNMT1 in imprint resetting or maintenance in the male germ line.

Male germ line stem cells: from cell biology to cell therapy

2003 ◽  
Vol 15 (6) ◽  
pp. 323 ◽  
Author(s):  
David Pei-Cheng Lin ◽  
Ming-Yu Chang ◽  
Bo-Yie Chen ◽  
Han-Hsin Chang
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Lines ◽  
Germ Cells ◽  
Germ Line ◽  
Current Status ◽  
Seminiferous Tubules ◽  
Male Germ Line ◽  
Male Germ Cells ◽  
Stem Cell Lines

Research using stem cells has several applications in basic biology and clinical medicine. Recent advances in the establishment of male germ line stem cells provided researchers with the ability to identify, isolate, maintain, expand and differentiate the spermatogonia, the primitive male germ cells, as cell lines under in vitro conditions. The ability to culture and manipulate stem cell lines from male germ cells has gradually facilitated research into spermatogenesis and male infertility, to an extent beyond that facilitated by the use of somatic stem cells. After the introduction of exogenous genes, the spermatogonial cells can be transplanted into the seminiferous tubules of recipients, where the transplanted cells can contribute to the offspring. The present review concentrates on the origin, life cycle and establishment of stem cell lines from male germ cells, as well as the current status of transplantation techniques and the application of spermatogonial stem cell lines.

The role of the Y chromosome in male infertility

2001 ◽  
Vol 3 (3) ◽  
pp. 1-16 ◽  
Author(s):  
Nabeel A. Affara
Keyword(s):  
Cell Differentiation ◽  
Male Infertility ◽  
Germ Cell ◽  
Candidate Gene ◽  
Y Chromosome ◽  
Comparative Data ◽  
Male Germ Cell ◽  
Functional Genes ◽  
Germ Cell Differentiation

It was suggested by Ronald Fisher in 1931 that genes that benefit the male (including those required for spermatogenesis) would accumulate on the Y chromosome. Following the discovery that microdeletions of the Y chromosome were associated with diverse spermatogenic phenotypes, at least three intervals that contain one or more genes controlling male germ-cell differentiation have been identified in humans. These intervals, named AZFa, AZFb and AZFc, have been mapped, cloned and examined in detail for the presence of functional genes. In this review, I have discussed the genes that map to the AZF intervals and the evidence indicating which ones are the most likely candidates underlying Y-linked male infertility. In addition, I have considered the analysis of key intervals on the mouse Y chromosome, where it provides comparative data supporting the role of a candidate gene in an infertility phenotype.

scholarly journals Haploid expression of a unique c-abl transcript in the mouse male germ line.

1985 ◽  
Vol 5 (7) ◽  
pp. 1791-1794 ◽  
Author(s):  
C Ponzetto ◽  
D J Wolgemuth
Keyword(s):  
Molecular Weight ◽  
Germ Cells ◽  
Germ Line ◽  
Low Molecular Weight ◽  
Male Germ Line ◽  
Predominant Species ◽  
Testicular Cells ◽  
Regulated Expression ◽  
Immature Mouse ◽  
Normal Differentiation

RNA from immature mouse testes was shown to lack a low-molecular-weight c-abl transcript previously noted to be the predominant species in adult testes. The developmental pattern of appearance of this c-abl variant was determined by analyzing RNA obtained from purified populations of testicular cells in different stages of spermatogenesis. The appearance of the c-abl testicular variant was coincident with the entry of the germ cells into their haploid state and suggested that the regulated expression of this proto-oncogene may be important in the normal differentiation of the male germ line.

scholarly journals AZFa candidate gene UTY and its X homologue UTX are expressed in human germ cells

2021 ◽  
Author(s):  
Peter H Vogt ◽  
Jutta Zimmer ◽  
Ulrike Bender ◽  
Thomas Strowitzki
Keyword(s):  
Germ Cell ◽  
Candidate Gene ◽  
Y Chromosome ◽  
Germ Cells ◽  
Protein Interactions ◽  
Germ Line ◽  
Primordial Germ Cells ◽  
Basal Membrane ◽  
Specific Protein ◽  
Disorders Of Sexual Development

The Ubiquitous Transcribed Y (UTY) AZFa candidate gene on the human Y chromosome and its paralog on the X chromosome, UTX, encode a histone lysine demethylase removing chromatin H3K27 methylation marks at genes transcriptional start sites for activation. Both proteins harbour the conserved Jumonji C (JmjC) domain, functional in chromatin metabolism, and an extended N-terminal tetratrico peptide repeat (TPR) block involved in specific protein-interactions. Specific antisera for human UTY and UTX proteins were developed to distinguish expression of both proteins in human germ cells by immunohistochemical experiments on appropriate tissue sections. In the male germ line, UTY was expressed in the fraction of A spermatogonia located at the basal membrane probably including spermatogonia stem cells. UTX expression was more spread in all spermatogonia and in early spermatids. In female germ line, UTX expression was found in the primordial germ cells of the ovary. UTY was also expressed during fetal male germ cell development, whereas UTX expression was visible only at distinct gestation weeks. Based on these results and the conserved neighboured location of UTY and DDX3Y in Yq11 found in mammals of distinct lineages, we conclude that UTY –like DDX3Y- is part of the Azoospermia factor a (AZFa) locus functioning in human spermatogonia to support the balance of their proliferation-differentiation rate before meiosis. Comparable UTY and DDX3Y expression was also found in gonadoblastoma and dysgerminoma cells found in germ cell nests of the dysgenetic gonads of individuals with disorders of sexual development and a Y chromosome in karyotype (DSD-XY). This confirms that AZFa overlaps with GBY, the Gonadoblastoma susceptibility Y locus, and includes the UTY gene.

scholarly journals 002.Human spermatozoa: fruits of creation, seed of doubt

2004 ◽  
Vol 16 (9) ◽  
pp. 2
Author(s):  
R. J. Aitken
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Dna Repair ◽  
Germ Cells ◽  
Oxidative Dna Damage ◽  
Germ Line ◽  
Early Embryo ◽  
Human Spermatozoa ◽  
Obstructive Azoospermia ◽  
Male Germ Line

Defective sperm function is the largest defined cause of human infertility, affecting one in twenty Australian males. Despite its prevalence, we are only just beginning to understand the underlying mechanisms. The past decade has seen two major advances in this field: (1) the discovery that Y chromosome deletions play a key role in the aetiology of non-obstructive azoospermia/oligozoospermia; and (2) recognition that oxidative stress can impact upon the functional competence of human spermatozoa through peroxidative damage to the sperm plasma membrane. Oxidative stress has also been found to disrupt the integrity of DNA in the male germ line and may represent an important mechanism by which environmental impacts on human health are mediated. Thus, paternal exposure to various toxicants (cigarette smoke, organic solvents, heavy metals) has been linked with oxidative DNA damage in spermatozoa and developmental defects, including cancer, in the F1 generation. The male germ line becomes particularly vulnerable to such factors during the post meiotic stages of differentiation. Pre-meiotic germ cells always have the option of undergoing apoptosis if DNA damage is severe. However, post meiotic germ cells have lost both the ability to mount an apoptotic response and the capacity for DNA repair. As a result, germ cells are particularly vulnerable to genotoxic agents during spermiogenesis and epididymal maturation. If the fertilizing capacity of the spermatozoa is retained following toxicant exposure, then DNA damage will be transferred to the zygote and must be repaired subsequently by the oocyte and/or early embryo. Aberrant DNA repair at this stage has the potential to create mutations that will compromise embryonic development and, ultimately, the normality of the offspring. Elucidating the causes of oxidative damage in spermatozoa should help resolve the aetiology of conditions such as male infertility, early pregnancy loss and childhood disease, including cancer.

Hypothesis: a Y-chromosomal gene causes gonadoblastoma in dysgenetic gonads

Development ◽  
1987 ◽  
Vol 101 (Supplement) ◽  
pp. 151-155 ◽  
Author(s):  
David C. Page
Keyword(s):  
Y Chromosome ◽  
Dna Hybridization ◽  
Physiological Function ◽  
Hybridization Analysis ◽  
Chromosomal Gene ◽  
Normal Males ◽  
Part Model ◽  
Human Y Chromosome

The role of the human Y chromosome in the etiology of gonadoblastoma, a gonadal neoplasm, is considered and a two-part model is presented. According to this hypothesis: (1) There is a gene on the Y chromosome that strongly predisposes dysgenetic gonads to develop gonadoblastomas (Page, 1986) and (2) this postulated GBY gene (GonadoBlastoma locus on Y chromosome) has some physiological function in normal males. GBY may, for example, function in or prior to spermatogenesis in normal testes. Y-DNA hybridization analysis of individuals with gonadoblastoma and partial deletions of the Y chromosome should be of use in testing this proposal. To date, such studies suggest that GBY maps to the region that includes deletion intervals 4B to 7, i.e. it is located near the centromere or on the long arm of the Y chromosome.

Germ cells of the mammalian female: A limited or renewable resource?

2021 ◽  
Author(s):  
Mathilde Hainaut ◽  
Hugh J Clarke
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Germ Cells ◽  
Germ Line ◽  
Marker Gene ◽  
Somatic Cells ◽  
Renewable Resource ◽  
Weight Of Evidence ◽  
Fetal Life

Abstract In many non-mammalian organisms, a population of germ-line stem cells supports continuing production of gametes during most or all the life of the individual, and germ-line stem cells are also present and functional in male mammals. Traditionally, however, they have been thought not to exist in female mammals, who instead generate all their germ cells during fetal life. Over the last several years, this dogma has been challenged by several reports, while supported by others. We describe and compare these conflicting studies with the aim of understanding how they came to opposing conclusions. We first consider studies that, by examining marker-gene expression, the fate of genetically marked cells, and consequences of depleting the oocyte population, addressed whether ovaries of post-natal females contain oogonial stem cells (OSC) that give rise to new oocytes. We next discuss whether ovaries contain cells that, even if inactive under physiological conditions, nonetheless possess OSC properties that can be revealed through cell-culture. We then examine studies of whether cells harvested after long-term culture of cells obtained from ovaries can, following transplantation into ovaries of recipient females, give rise to oocytes and offspring. Finally, we note studies where somatic cells have been re-programmed to acquire a female germ-cell fate. We conclude that the weight of evidence strongly supports the traditional interpretation that germ-line stem cells do not exist post-natally in female mammals. However, the ability to generate germ cells from somatic cells in vitro establishes a method to generate new gametes from cells of post-natal mammalian females.

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