scholarly journals Germ cell loss is associated with fading Lin28a expression in a mouse model for Klinefelter's syndrome

Reproduction ◽  
2014 ◽  
Vol 147 (3) ◽  
pp. 253-264 ◽  
Author(s):  
Steffi Werler ◽  
Hannah Demond ◽  
Oliver S Damm ◽  
Jens Ehmcke ◽  
Ralf Middendorff ◽  
...  
Keyword(s):  
Mouse Model ◽  
Germ Cell ◽  
Germ Cells ◽  
Germ Line ◽  
Cell Loss ◽  
Klinefelter’S Syndrome ◽  
Klinefelter's Syndrome ◽  
Proliferating Cells ◽  
Underlying Causes ◽  
Marker Expression

Klinefelter's syndrome is a male sex-chromosomal disorder (47,XXY), causing hypogonadism, cognitive and metabolic deficits. The majority of patients are infertile due to complete germ cell loss after puberty. As the depletion occurs during development, the possibilities to study the underlying causes in humans are limited. In this study, we used the 41,XXY* mouse model to characterise the germ line postnatally. We examined marker expression of testicular cells focusing on the spermatogonial stem cells (SSCs) and found that the number of germ cells was approximately reduced fivefold at day 1pp in the 41,XXY* mice, indicating the loss to start prenatally. Concurrently, immunohistochemical SSC markers LIN28A and PGP9.5 also showed decreased expression on day 1pp in the 41,XXY* mice (48.5 and 38.9% of all germ cells were positive), which dropped to 7.8 and 7.3% on 3dpp, and were no longer detectable on days 5 and 10pp respectively. The differences in PCNA-positive proliferating cells in XY* and XXY* mice dramatically increased towards day 10pp. The mRNA expression of the germ cell markers Lin28a (Lin28), Pou5f1 (Oct4), Utf1, Ddx4 (Vasa), Dazl, and Fapb1 (Sycp3) was reduced and the Lin28a regulating miRNAs were deregulated in the 41,XXY* mice. We suggest a model for the course of germ cell loss starting during the intrauterine period. Neonatally, SSC marker expression by the already lowered number of spermatogonia is reduced and continues fading during the first postnatal week, indicating the surviving cells of the SSC population to be disturbed in their stem cell characteristics. Subsequently, the entire germ line is then generally lost when entering meiosis.

GATA-like protein-1 (GLP-1) is required for normal germ cell development during embryonic oogenesis

Reproduction ◽  
2011 ◽  
Vol 141 (2) ◽  
pp. 173-181 ◽  
Author(s):  
Tamara J Strauss ◽  
Diego H Castrillon ◽  
Stephen R Hammes
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Germ Line ◽  
Primordial Follicle ◽  
Cell Loss ◽  
Basement Membranes ◽  
Cell Protein ◽  
Null Mouse ◽  
Cell Functions ◽  
Expression Of Genes

Oogenesis and primordial follicle formation are tightly linked processes, requiring organized and precisely timed communication between somatic and germ cells. Deviations in ovarian cell cross talk, or aberrant gene expression within one of the cell populations, can lead to follicle loss or dysfunction, resulting in infertility. Expression of GATA-like protein-1 (GLP-1) in ovarian somatic cells is required for normal fertility in female mice, as GLP-1 deficiency leads to the absence of oocytes at birth. However, the timing and nature of this germ cell loss is not well understood. In this study, we characterize the embryonic germ cell loss in GLP-1 null mice. Quantitative PCR demonstrates that ovarian Glp-1 mRNA is expressed in a bimodal pattern during embryogenesis, peaking at E13.5–14.5 and again at birth. In contrast, adult ovaries express low but detectable levels of Glp-1 mRNA. Analysis of developing GLP-1 null mouse ovaries shows that germ cells are appropriately specified and migrate normally to nascent gonads. Upon arrival at the gonad, precocious loss of germ cells begins at around E13.5. This loss is completed by birth and is accompanied by defects in the expression of genes associated with meiotic entry. Interestingly, somatic pregranulosa cells still form basement membranes surrounding germ line cysts and express mRNA encoding paracrine signaling molecules that communicate with oocytes, albeit at lower levels than normal. Together, these data imply that the somatic cell protein GLP-1 is not necessary for many pregranulosa cell functions but is required for germ cell survival.

scholarly journals BCL2-modifying factor promotes germ cell loss during murine oogenesis

Reproduction ◽  
2016 ◽  
Vol 151 (5) ◽  
pp. 553-562 ◽  
Author(s):  
Kavitha Vaithiyanathan ◽  
Seng H Liew ◽  
Nadeen Zerafa ◽  
Thilini Gamage ◽  
Michele Cook ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Germ Line ◽  
Cell Loss ◽  
Regulatory Proteins ◽  
Primordial Follicles ◽  
Large Numbers ◽  
Female Germ Line ◽  
Low Levels

Abstract Apoptosis plays a prominent role during ovarian development by eliminating large numbers of germ cells from the female germ line. However, the precise mechanisms and regulatory proteins involved in germ cell death are yet to be determined. In this study, we characterised the role of the pro-apoptotic BH3-only protein, BCL2-modifying factor (BMF), in germ cell apoptosis in embryonic and neonatal mouse ovaries. BMF protein was immunohistochemically localised to germ cells at embryonic days 15.5 (E15.5) and E17.5 and postnatal day 1 (PN1), coincident with entry into the meiotic prophase, but was undetectable at E13.5, and only present at low levels at PN3 and PN5. Consistent with this expression pattern, loss of BMF in female mice was associated with a decrease in apoptosis at E15.5 and E17.5. Furthermore, increased numbers of germ cells were found in ovaries from Bmf−/− mice compared with WT animals at E15.5 and PN1. However, germ cell numbers were comparable between Bmf−/− and WT ovaries at PN3, PN5 and PN10. Collectively, these data indicate that BMF mediates foetal oocyte loss and its action limits the maximal number of germ cells attained in the developing ovary, but does not influence the number of primordial follicles initially established in ovarian reserve.

Progressive depletion of germ cells in a man with nonmosaic Klinefelter's syndrome: optimal time for sperm recovery

Urology ◽  
2004 ◽  
Vol 63 (2) ◽  
pp. 380-381 ◽  
Author(s):  
Yung Ming Lin ◽  
William J Huang ◽  
Johnny Shinn Nan Lin ◽  
Pao Lin Kuo
Keyword(s):  
Germ Cells ◽  
Optimal Time ◽  
Klinefelter’S Syndrome ◽  
Klinefelter's Syndrome ◽  
Sperm Recovery

The fog-3 gene and regulation of cell fate in the germ line of Caenorhabditis elegans.

Genetics ◽  
1995 ◽  
Vol 139 (2) ◽  
pp. 561-577 ◽  
Author(s):  
R E Ellis ◽  
J Kimble
Keyword(s):  
Caenorhabditis Elegans ◽  
Germ Cell ◽  
Sexual Identity ◽  
Cell Fate ◽  
Germ Cells ◽  
Regulatory Network ◽  
Germ Line ◽  
The Other ◽  
Nematode Caenorhabditis Elegans ◽  
Inhibitory Interactions

Abstract In the nematode Caenorhabditis elegans, germ cells normally adopt one of three fates: mitosis, spermatogenesis or oogenesis. We have identified and characterized the gene fog-3, which is required for germ cells to differentiate as sperm rather than as oocytes. Analysis of double mutants suggests that fog-3 is absolutely required for spermatogenesis and acts at the end of the regulatory hierarchy controlling sex determination for the germ line. By contrast, mutations in fog-3 do not alter the sexual identity of other tissues. We also have characterized the null phenotype of fog-1, another gene required for spermatogenesis; we demonstrate that it too controls the sexual identity of germ cells but not of other tissues. Finally, we have studied the interaction of these two fog genes with gld-1, a gene required for germ cells to undergo oogenesis rather than mitosis. On the basis of these results, we propose that germ-cell fate might be controlled by a set of inhibitory interactions among genes that specify one of three fates: mitosis, spermatogenesis or oogenesis. Such a regulatory network would link the adoption of one germ-cell fate to the suppression of the other two.

Expression of selected genes escaping from X inactivation in the 41, XXY* mouse model for Klinefelter’s syndrome

2011 ◽  
Vol 100 (6) ◽  
pp. 885-891 ◽  
Author(s):  
Steffi Werler ◽  
Andreas Poplinski ◽  
Jörg Gromoll ◽  
Joachim Wistuba
Keyword(s):  
Mouse Model ◽  
X Inactivation ◽  
Klinefelter’S Syndrome ◽  
Klinefelter's Syndrome

A Case of Primary Mediastinal Germ Cell Tumor Associated with Klinefelter's Syndrome

1996 ◽  
Vol 43 (6) ◽  
pp. 1035
Author(s):  
Yong Jo Kim ◽  
Gyo Seon Kwun ◽  
Young Wo Lee ◽  
Kyung Tae Kim ◽  
Yeon Hee Park ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Cell Tumor ◽  
Klinefelter’S Syndrome ◽  
Klinefelter's Syndrome ◽  
Mediastinal Germ Cell Tumor

Klinefelter's syndrome associated with mediastinal germ cell neoplasms.

1987 ◽  
Vol 5 (8) ◽  
pp. 1290-1294 ◽  
Author(s):  
C R Nichols ◽  
N A Heerema ◽  
C Palmer ◽  
P J Loehrer ◽  
S D Williams ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Case Reports ◽  
Germ Cell Tumors ◽  
Cell Tumor ◽  
Klinefelter’S Syndrome ◽  
Klinefelter's Syndrome ◽  
Cell Neoplasm ◽  
Mediastinal Germ Cell Tumor ◽  
Mediastinal Germ Cell Tumors

Several case reports have suggested an association of primary mediastinal germ cell tumor (PMGCT) and Klinefelter's syndrome (KS). In an effort to confirm this association, 22 patients with mediastinal germ cell tumors had chromosome studies performed in a prospective fashion. Five patients (22%) had karyotypic or pathologic evidence of KS. All of the patients with KS had germ cell tumors of the nonseminomatous subtype and were relatively young (median age, 15 years). The literature confirms the findings of a young median age (18 years), nonseminomatous subtype, and mediastinal location of the germ cell neoplasm. We conclude that patients with KS are predisposed to the development of mediastinal nonseminomatous germ cell cancers.

scholarly journals PUMA regulates germ cell loss and primordial follicle endowment in mice

Reproduction ◽  
2014 ◽  
Vol 148 (2) ◽  
pp. 211-219 ◽  
Author(s):  
Michelle Myers ◽  
F Hamish Morgan ◽  
Seng H Liew ◽  
Nadeen Zerafa ◽  
Thilini Upeksha Gamage ◽  
...  
Keyword(s):  
Cell Death ◽  
Germ Cell ◽  
Germ Cells ◽  
Ovarian Development ◽  
Fold Increase ◽  
Cell Loss ◽  
Postnatal Life ◽  
Critical Determinant ◽  
Primordial Follicles ◽  
Female Mice

The number of primordial follicles initially established within the ovary is influenced by the extent of germ cell death during foetal ovarian development, but the mechanisms that mediate this death have not been fully uncovered. In this study, we identified BBC3 (PUMA) (p53 upregulated modulator of apoptosis, also known as BCL2-binding component 3), a pro-apoptotic BH3-only protein belonging to the BCL2 family, as a critical determinant of the number of germ cells during ovarian development. Targeted disruption of the Bbc3 gene revealed a significant increase in the number of germ cells as early as embryonic day 13.5. The number of germ cells remained elevated in Bbc3−/− female mice compared with WT female mice throughout the remainder of embryonic and early postnatal life, resulting in a 1.9-fold increase in the number of primordial follicles in the ovary on postnatal day 10. The increase in the number of germ cells observed in the ovaries of Bbc3−/− mice could not be attributed to the altered proliferative activity of germ cells within the ovaries. Furthermore, BBC3 was found to be not required for the massive germ cell loss that occurs during germ cell nest breakdown. Our data indicate that BBC3 is a critical regulator of germ cell death that acts during the migratory phase of oogenesis or very soon after the arrival of germ cells in the gonad and that BBC3-mediated cell death limits the number of primordial follicles established in the initial ovarian reserve.

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