scholarly journals Two Y Genes Can Replace the Entire Y Chromosome for Assisted Reproduction in the Mouse

Science ◽  
2013 ◽  
Vol 343 (6166) ◽  
pp. 69-72 ◽  
Author(s):  
Yasuhiro Yamauchi ◽  
Jonathan M. Riel ◽  
Zoia Stoytcheva ◽  
Monika A. Ward
Keyword(s):  
Male Infertility ◽  
Y Chromosome ◽  
Assisted Reproduction ◽  
Germ Cells ◽  
Male Reproduction ◽  
Fetal Life ◽  
Human Male ◽  
Determinant Factor ◽  
Spermatogonial Proliferation ◽  
Live Mouse

The Y chromosome is thought to be important for male reproduction. We have previously shown that, with the use of assisted reproduction, live offspring can be obtained from mice lacking the entire Y chromosome long arm. Here, we demonstrate that live mouse progeny can also be generated by using germ cells from males with the Y chromosome contribution limited to only two genes, the testis determinant factorSryand the spermatogonial proliferation factorEif2s3y.Sryis believed to function primarily in sex determination during fetal life.Eif2s3ymay be the only Y chromosome gene required to drive mouse spermatogenesis, allowing formation of haploid germ cells that are functional in assisted reproduction. Our findings are relevant, but not directly translatable, to human male infertility cases.

DECREASED AMOUNTS OF DESOXYRIBOSE NUCLEIC ACID (DNA) IN MALE GERM CELLS AS A POSSIBLE CAUSE OF HUMAN MALE INFERTILITY

1956 ◽  
Vol 6 (2) ◽  
pp. 272-278
Author(s):  
Cecilie Leuchtenberger ◽  
D.R. Weir ◽  
F. Schrader ◽  
R. Leuchtenberger
Keyword(s):  
Nucleic Acid ◽  
Male Infertility ◽  
Germ Cells ◽  
Male Germ Cells ◽  
Human Male ◽  
Possible Cause

Specific Expression of VCY2 in Human Male Germ Cells and Its Involvement in the Pathogenesis of Male Infertility

2003 ◽  
Vol 69 (3) ◽  
pp. 746-751 ◽  
Author(s):  
J.Y.M. Tse ◽  
E.Y.M. Wong ◽  
A.N.Y. Cheung ◽  
W.S. O ◽  
P.C. Tam ◽  
...  
Keyword(s):  
Male Infertility ◽  
Germ Cells ◽  
Specific Expression ◽  
Male Germ Cells ◽  
Human Male

scholarly journals Loss of protein phosphatase 1cγ (PPP1CC) leads to impaired spermatogenesis associated with defects in chromatin condensation and acrosome development: an ultrastructural analysis

Reproduction ◽  
2010 ◽  
Vol 139 (6) ◽  
pp. 1021-1029 ◽  
Author(s):  
Nicole Forgione ◽  
A Wayne Vogl ◽  
Susannah Varmuza
Keyword(s):  
Electron Microscopy ◽  
Male Infertility ◽  
Germ Cells ◽  
Chromatin Condensation ◽  
Light And Electron Microscopy ◽  
Testicular Development ◽  
Tissue Architecture ◽  
Genetic Abnormality ◽  
Human Male ◽  
Testicular Failure

Human male infertility affects ∼5% of men, with one-third suffering from testicular failure, likely the result of an underlying genetic abnormality that disrupts spermatogenesis during development. Mouse models of male infertility such as thePpp1ccknockout mouse display very similar phenotypes to humans with testicular failure. MalePpp1ccmutant mice are sterile due to disruptions in spermatogenesis that begin during prepubertal testicular development, and continue into adulthood, often resulting in loss of germ cells to the point of Sertoli cell-only syndrome. The current study employs light and electron microscopy to identify new morphological abnormalities inPpp1ccmutant seminiferous epithelium. This study reveals that germ cells become delayed in their development around stages VII and VIII of spermatogenesis. Loss of these cells likely results in the reduced numbers of elongating spermatids and spermatozoa previously observed in mutant animals. Interestingly,Ppp1ccmutants also display reduced numbers of spermatogonia compared with their wild-type counterparts. Using electron microscopy, we have shown that junction complexes inPpp1ccmutants are ultrastructurally normal, and therefore do not contribute to the breakdown in tissue architecture seen in mutants. Electron microscopy revealed major acrosomal and chromatin condensation defects inPpp1ccmutants. Our observations are discussed in the context of known molecular changes inPpp1ccmutant testes.

scholarly journals Long non-coding RNAs (lncRNAs) in spermatogenesis and male infertility

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Meghali Joshi ◽  
Singh Rajender
Keyword(s):  
Male Infertility ◽  
Germ Cell ◽  
Germ Cells ◽  
Motile Sperm ◽  
Rna Seq ◽  
Small Noncoding Rnas ◽  
Cellular Processes ◽  
Human Male ◽  
Non Coding Rnas

Abstract Background Long non-coding RNAs (lncRNAs) have a size of more than 200 bp and are known to regulate a host of crucial cellular processes like proliferation, differentiation and apoptosis by regulating gene expression. While small noncoding RNAs (ncRNAs) such as miRNAs, siRNAs, Piwi-interacting RNAs have been extensively studied in male germ cell development, the role of lncRNAs in spermatogenesis remains largely unknown. Objective In this article, we have reviewed the biology and role of lncRNAs in spermatogenesis along with the tools available for data analysis. Results and conclusions Till date, three microarray and four RNA-seq studies have been undertaken to identify lncRNAs in mouse testes or germ cells. These studies were done on pre-natal, post-natal, adult testis, and different germ cells to identify lncRNAs regulating spermatogenesis. In case of humans, five RNA-seq studies on different germ cell populations, including two on sperm, were undertaken. We compared three studies on human germ cells to identify common lncRNAs and found 15 lncRNAs (LINC00635, LINC00521, LINC00174, LINC00654, LINC00710, LINC00226, LINC00326, LINC00494, LINC00535, LINC00616, LINC00662, LINC00668, LINC00467, LINC00608, and LINC00658) to show consistent differential expression across these studies. Some of the targets of these lncRNAs included CENPB, FAM98B, GOLGA6 family, RPGR, TPM2, GNB5, KCNQ10T1, TAZ, LIN28A, CDKN2B, CDKN2A, CDKN1A, CDKN1B, CDKN1C, EZH2, SUZ12, VEGFA genes. A lone study on human male infertility identified 9879 differentially expressed lncRNAs with three (lnc32058, lnc09522, and lnc98497) of them showing specific and high expression in immotile sperm in comparison to normal motile sperm. A few lncRNAs (Mrhl, Drm, Spga-lncRNAs, NLC1-C, HongrES2, Tsx, LncRNA-tcam1, Tug1, Tesra, AK015322, Gm2044, and LncRNA033862) have been functionally validated for their roles in spermatogenesis. Apart from rodents and humans, studies on sheep and bull have also identified lncRNAs potentially important for spermatogenesis. A number of these non-coding RNAs are strong candidates for further research on their roles in spermatogenesis.

scholarly journals Analysis of Y chromosome microdeletions and CFTR gene mutations as genetic markers of infertility in Serbian men

2007 ◽  
Vol 64 (4) ◽  
pp. 253-256 ◽  
Author(s):  
Jelena Dinic ◽  
Jelena Kusic ◽  
Аleksandra Nikolic ◽  
Aleksandra Divac ◽  
Momcilo Ristanovic ◽  
...  
Keyword(s):  
Male Infertility ◽  
Y Chromosome ◽  
Assisted Reproduction ◽  
Sperm Quality ◽  
Gene Mutations ◽  
Cftr Gene ◽  
Common Mutation ◽  
Infertile Men ◽  
Y Chromosome Microdeletions ◽  
Cftr Gene Mutations

Background/Aim. Impaired fertility of a male partner is the main cause of infertility in up to one half of all infertile couples. At the genetic level, male infertility can be caused by chromosome aberrations or gene mutations. The presence and types of Y chromosome microdeletions and cystic fybrosis transmembrane conductance regulator (CFTR) gene mutations as genetic cause of male infertility was tested in Serbian men. The aim of this study was to analyze CFTR gene mutations and Y chromosome microdelations as potential causes of male infertility in Serbian patients, as well as to test the hypothesis that CFTR mutations in infertile men are predominantly located in the several last exons of the gene. Methods. This study has encompassed 33 men with oligo- or azoospermia. The screening for Y chromosome microdeletions in the azoospermia factor (AZF) region was performed by multiplex PCR analysis. The screening of the CFTR gene was performed by denaturing gradient gel electrophoresis (DGGE) method. Results. Deletions on Y chromosome were detected in four patients, predominantly in AZFc region (four of total six deletions). Mutations in the CFTR gene were detected on eight out of 66 analyzed chromosomes of infertile men. The most common mutation was F508del (six of total eight mutations). Conclusion. This study confirmed that both Y chromosome microdeletions and CFTR gene mutations played important role in etiology of male infertility in Serbian infertile men. Genetic testing for Y chromosome microdeletions and CFTR gene mutations has been introduced in routine diagnostics and offered to couples undergoing assisted reproduction techniques. Considering that both the type of Y chromosome microdeletion and the type of CFTR mutation have a prognostic value, it is recommended that AZF and CFTR genotyping should not only be performed in patients with reduced sperm quality before undergoing assisted reproduction, but also for the purpose of preimplantation and prenatal diagnostics in couples in which in vitro fertilization has been performed successfully.

scholarly journals TRIM71 deficiency causes germ cell loss during mouse embryogenesis and promotes human male infertility

2021 ◽  
Author(s):  
Lucia A. Torres-Fernández ◽  
Jana Emich ◽  
Yasmine Port ◽  
Sibylle Mitschka ◽  
Marius Wöste ◽  
...  
Keyword(s):  
Male Infertility ◽  
Germ Cell ◽  
Germ Cells ◽  
Cell Loss ◽  
Seminiferous Tubules ◽  
Obstructive Azoospermia ◽  
Sequencing Analysis ◽  
Mouse Embryogenesis ◽  
Human Male

AbstractMutations affecting the germline can result in infertility or the generation of germ cell tumors (GCT), highlighting the need to identify and characterize the genes controlling the complex molecular network orchestrating germ cell development. TRIM71 is a stem cell-specific factor essential for embryogenesis, and its expression has been reported in GCT and adult mouse testes. To investigate the role of TRIM71 in mammalian germ cell embryonic development, we generated a germline-specific conditional Trim71 knockout mouse (cKO) using the early primordial germ cell (PGC) marker Nanos3 as a Cre-recombinase driver. cKO mice are infertile, with male mice displaying a Sertoli cell-only (SCO) phenotype, which in humans is defined as a specific subtype of non-obstructive azoospermia characterized by the absence of developing germ cells in the testes’ seminiferous tubules. Infertility originates during embryogenesis, as the SCO phenotype was already apparent in neonatal mice. The in vitro differentiation of mouse embryonic stem cells (ESCs) into PGC-like cells (PGCLCs) revealed reduced numbers of PGCLCs in Trim71-deficient cells. Furthermore, in vitro growth competition assays with wild type and CRISPR/Cas9-generated TRIM71 mutant NCCIT cells, a human GCT-derived cell line which we used as a surrogate model for proliferating PGCs, showed that TRIM71 promotes NCCIT cell proliferation and survival. Our data collectively suggest that germ cell loss in cKO mice results from combined defects during the specification and maintenance of PGCs prior to their sex determination in the genital ridges. Last, via exome sequencing analysis, we identified several TRIM71 variants in a cohort of infertile men, including a loss-of-function variant in a patient with SCO phenotype. Our work reveals for the first time an association of TRIM71 variants with human male infertility, and uncovers further developmental roles for TRIM71 in the generation and maintenance of germ cells during mouse embryogenesis.

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.

scholarly journals Human male infertility and Y chromosome deletions: role of the AZF-candidate genes DAZ, RBM and DFFRY

1999 ◽  
Vol 14 (7) ◽  
pp. 1710-1716 ◽  
Author(s):  
A. Ferlin ◽  
E. Moro ◽  
A. Garolla ◽  
C. Foresta
Keyword(s):  
Male Infertility ◽  
Candidate Genes ◽  
Y Chromosome ◽  
Human Male ◽  
Chromosome Deletions
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