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

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.

1985 ◽  
Vol 5 (7) ◽  
pp. 1791-1794
Author(s):  
C Ponzetto ◽  
D J Wolgemuth

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.


Development ◽  
1990 ◽  
Vol 109 (4) ◽  
pp. 911-923 ◽  
Author(s):  
A. Orr-Urtreger ◽  
A. Avivi ◽  
Y. Zimmer ◽  
D. Givol ◽  
Y. Yarden ◽  
...  

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.


Reproduction ◽  
2007 ◽  
Vol 134 (3) ◽  
pp. 445-453 ◽  
Author(s):  
Jiří Kalina ◽  
Filip Šenigl ◽  
Alena Mičáková ◽  
Jitka Mucksová ◽  
Jana Blažková ◽  
...  

Chicken testicular cells, including spermatogonia, transplanted into the testes of recipient cockerels sterilized by repeated γ-irradiation repopulate the seminiferous epithelium and resume the exogenous spermatogenesis. This procedure could be used to introduce genetic modifications into the male germ line and generate transgenic chickens. In this study, we present a successful retroviral infection of chicken testicular cells and consequent transduction of the retroviral vector into the sperm of recipient cockerels. A vesicular stomatitis virus glycoprotein G-pseudotyped recombinant retroviral vector, carrying the enhanced green fluorescent protein reporter gene was applied to the short-term culture of dispersed testicular cells. The efficiency of infection and the viability of infected cells were analyzed by flow cytometry. No significant CpG methylation was detected in the infected testicular cells, suggesting that epigenetic silencing events do not play a role at this stage of germ line development. After transplantation into sterilized recipient cockerels, these retrovirus-infected testicular cells restored exogenous spermatogenesis within 9 weeks with approximately the same efficiency as non-infected cells. Transduction of the reporter gene encoding the green fluorescent protein was detected in the sperms of recipient cockerels with restored spermatogenesis. Our data demonstrate that, similarly as in mouse and rat, the transplantation of retrovirus-infected spermatogonia provides an efficient system to introduce genes into the chicken male germ line.


2003 ◽  
Vol 15 (6) ◽  
pp. 323 ◽  
Author(s):  
David Pei-Cheng Lin ◽  
Ming-Yu Chang ◽  
Bo-Yie Chen ◽  
Han-Hsin Chang

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.


2010 ◽  
Vol 365 (1546) ◽  
pp. 1653-1662 ◽  
Author(s):  
Debra J. Wolgemuth ◽  
Shelby S. Roberts

Key components of the cell cycle machinery are the regulatory subunits, the cyclins, and their catalytic partners the cyclin-dependent kinases. Regulating the cell cycle in the male germ line cells represents unique challenges for this machinery given the constant renewal of gametes throughout the reproductive lifespan and the induction of the unique process of meiosis, a highly specialized kind of cell division. With challenges come opportunities to the critical eye, recognizing that understanding these specialized modes of regulation will provide considerable insight into both normal differentiation as well as disease conditions, including infertility and oncogenesis.


1990 ◽  
Vol 111 (5) ◽  
pp. 1785-1792 ◽  
Author(s):  
Z F Zakeri ◽  
W J Welch ◽  
D J Wolgemuth

The properties and inducibility of the heat shock protein 70 (hsp 70) gene products were examined during differentiation of mouse testicular cells by one and two-dimensional gel electrophoresis and immunoblotting. Low levels of the 72- and 73-kD heat shock proteins normally found in mouse cell lines were detected in the mouse testis. A novel isoform with a relative molecular mass of 73 kD (called 73T) was also observed, in the presence or absence of heat shock. 73T was shown to be produced by germ cells since it was not detected in testes from mutant mice devoid of germ cells. Furthermore, 73T was found only in adult mouse testicular cells, not in testes from animals that lack meiotic germ cells. 73T was synthesized in enriched cell populations of both meiotic prophase and postmeiotic cells, but was not inducible by in vitro heat shock. In the adult testis, low levels of the bona fide 72-kD heat-inducible (hsp72) were induced in response to elevated temperatures. In contrast, in testes from animals in which only somatic cells and premeiotic germ cells were present, there was a substantial induction of hsp 72. It is suggested that hsp 72 is inducible in the somatic compartment and possibly in the premeiotic germ cells, but not in germ cells which have entered meiosis and which are expressing members of the hsp 70 gene family in a developmentally regulated fashion.


2004 ◽  
Vol 16 (9) ◽  
pp. 2
Author(s):  
R. J. Aitken

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.


Reproduction ◽  
2018 ◽  
Vol 156 (3) ◽  
pp. 269-282 ◽  
Author(s):  
Miguel J Xavier ◽  
Lisa A Mitchell ◽  
Kristen E McEwan ◽  
Rodney J Scott ◽  
R John Aitken

The Big Blue λSelect-cII selection system has been employed along with whole-exome sequencing to examine the susceptibility of the male germ line to mutation in two challenging situations (i) exposure to a chemotherapeutic regime including bleomycin, etoposide and cis-platinum (BEP) and (ii) the ageing process. A 3-week exposure to BEP induced complete azoospermia associated with a loss of developing germ cells and extensive vacuolization of Sertoli cell cytoplasm. Following cessation of treatment, spermatozoa first appeared in the caput epididymis after 6 weeks and by 12 weeks motile spermatozoa could be recovered from the cauda, although the count (P < 0.001) and motility (P < 0.01) of these cells were significantly reduced and superoxide generation was significantly elevated (P < 0.001). Despite this increase in free radical generation, no evidence of chromatin instability was detected in these spermatozoa. Furthermore, embryos obtained from females mated at this 12-week time point showed no evidence of an increased mutational load. Similarly, progressive ageing of Big Blue mice had no impact on the quality of the spermatozoa, fertility or mutation frequency in the offspring despite a significant increase in the mutational load carried by somatic tissues such as the liver (P < 0.05). We conclude that the male germ line is highly resistant to mutation in keeping with the disposable soma hypothesis, which posits that genetic integrity in the germ cells will be maintained at the expense of the soma, in light of the former’s sentinel position in safeguarding the stability of the genome.


2009 ◽  
Vol 29 (22) ◽  
pp. 6128-6139 ◽  
Author(s):  
Maia Dorsett ◽  
Tim Schedl

ABSTRACT During normal development as well as in diseased states such as cancer, extracellular “niches” often provide cues to proximal cells and activate intracellular pathways. Activation of such signaling pathways in turn instructs cellular proliferation and differentiation. In the Caenorhabditis elegans gonad, GLP-1/Notch signaling instructs germ line stem cells to self-renew through mitotic cell division. As germ cells progressively move out of the niche, they differentiate by entering meiosis and eventually form gametes. In this model system, we uncovered an unexpected role for the dynein motor complex in promoting normal differentiation of proliferating germ cells. We demonstrate that dynein light chain 1 (DLC-1) and its partner, dynein heavy chain 1, inhibit the proliferative cell fate, in part through regulation of METT-10, a conserved putative methyltransferase. We show that DLC-1 physically interacts with METT-10 and promotes both its overall levels and nuclear accumulation. Our results add a new dimension to the processes controlled by the dynein motor complex, demonstrating that dynein can act as an antiproliferative factor.


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