Bone morphogenetic protein 8A plays a role in the maintenance of spermatogenesis and the integrity of the epididymis

Development ◽  
1998 ◽  
Vol 125 (6) ◽  
pp. 1103-1112 ◽  
Author(s):  
G.Q. Zhao ◽  
L. Liaw ◽  
B.L. Hogan
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Targeted Mutagenesis ◽  
Chromosome 4 ◽  
Female Reproduction ◽  
Cell Degeneration ◽  
Male Germ Cells ◽  
Morphogenetic Protein ◽  
Germ Cell Degeneration

The murine Bmp8a and Bmp8b genes are tightly linked on mouse chromosome 4 and have similar expression during reproduction. Previous studies have shown that targeted mutagenesis of Bmp8b causes male infertility due to germ cell degeneration. To investigate the function of Bmp8a, we have inactivated the gene by homologous recombination. Heterozygous and homozygous Bmp8a mutants reveal normal embryonic and postnatal development. Despite high levels of Bmp8a expression in the deciduum, homozygous mutant females have normal fertility, suggesting that the gene is not essential for female reproduction. Bmp8a and Bmp8b are expressed in similar patterns in male germ cells. Unlike homozygous Bmp8btm1 mutants, homozygous Bmp8atm1 males do not show obvious germ cell defects during the initiation of spermatogenesis. However, germ cell degeneration is observed in 47% of adult homozygous Bmp8atm1 males, establishing a role of Bmp8a in the maintenance of spermatogenesis. A small proportion of the mating homozygous Bmp8atm1 males also show degeneration of the epididymal epithelium, indicating a novel role for BMPs in the control of epididymal function.

scholarly journals Overexpression of peroxisomal testis-specific 1 protein induces germ cell apoptosis and leads to infertility in male mice

2011 ◽  
Vol 22 (10) ◽  
pp. 1766-1779 ◽  
Author(s):  
Karina Kaczmarek ◽  
Maja Studencka ◽  
Andreas Meinhardt ◽  
Krzysztof Wieczerzak ◽  
Sven Thoms ◽  
...  
Keyword(s):  
Cell Death ◽  
Germ Cell ◽  
Germ Cells ◽  
Specific Gene ◽  
Male Mice ◽  
Terminal Part ◽  
Male Germ Cells ◽  
Germ Cell Apoptosis ◽  
Induced Apoptosis

 Peroxisomal testis-specific 1 gene (Pxt1) is the only male germ cell–specific gene that encodes a peroxisomal protein known to date. To elucidate the role of Pxt1 in spermatogenesis, we generated transgenic mice expressing a c-MYC-PXT1 fusion protein under the control of the PGK2 promoter. Overexpression of Pxt1 resulted in induction of male germ cells’ apoptosis mainly in primary spermatocytes, finally leading to male infertility. This prompted us to analyze the proapoptotic character of mouse PXT1, which harbors a BH3-like domain in the N-terminal part. In different cell lines, the overexpression of PXT1 also resulted in a dramatic increase of apoptosis, whereas the deletion of the BH3-like domain significantly reduced cell death events, thereby confirming that the domain is functional and essential for the proapoptotic activity of PXT1. Moreover, we demonstrated that PXT1 interacts with apoptosis regulator BAT3, which, if overexpressed, can protect cells from the PXT1-induced apoptosis. The PXT1-BAT3 association leads to PXT1 relocation from the cytoplasm to the nucleus. In summary, we demonstrated that PXT1 induces apoptosis via the BH3-like domain and that this process is inhibited by BAT3.

Evaluation of degenerating germ cells in normal juvenile mice

Genome ◽  
2009 ◽  
Vol 52 (10) ◽  
pp. 891-896 ◽  
Author(s):  
Anastassia Trifonova ◽  
Peter B. Moens
Keyword(s):  
Cell Death ◽  
Germ Cell ◽  
Germ Cells ◽  
Normal Component ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Electron Microscopic ◽  
Cell Degeneration ◽  
Novel Approach ◽  
Two Generations ◽  
Germ Cell Degeneration

Absence of spermiogenesis in mice with meiotic defects complicates the staging of meiotic arrest using light microscopy. Consequently, new methodologies are required to establish accurate relationships among germ cells. In this study, we utilized a novel approach to analyze germ cell degeneration in juvenile mice. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in combination with meiosis-specific antibodies. Germ cell degeneration is a normal component of early spermatogenesis in juvenile mice. The incidence of germ cell death was monitored at various postnatal ages of mice using the TUNEL assay to quantify the incidence of apoptosis. Cell death occurred predominantly at 15.5 days after birth. It was found that groups of apoptotic cells were apparent in tubules containing two generations of spermatocytes that form in two progressive cohorts. Electron microscopic observations further illustrated that the majority of cells in the first cohort are in late pachytene, while groups of cells in the second cohort can degenerate in early pachytene. The methodology utilized in this study is significant because it allows one to accurately determine the point at which germ cells arrest. Consequently, we believe that these methods can be applied to study animals with meiotic defects that prevent spermiogenesis.

Germ-cell degeneration in experimental unilateral cryptorchidism: role of apoptosis

1998 ◽  
Vol 14 (1-2) ◽  
pp. 9-13 ◽  
Author(s):  
Z. Q. Wang ◽  
T. Todani ◽  
Y. Watanabe ◽  
A. Toki ◽  
K. Ogura ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Degeneration ◽  
Unilateral Cryptorchidism ◽  
Germ Cell Degeneration

scholarly journals Nodal Signaling Regulates the Entry into Meiosis in Fetal Germ Cells

Endocrinology ◽  
2012 ◽  
Vol 153 (5) ◽  
pp. 2466-2473 ◽  
Author(s):  
Benoit Souquet ◽  
Sophie Tourpin ◽  
Sébastien Messiaen ◽  
Delphine Moison ◽  
René Habert ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Target Genes ◽  
Normal Male ◽  
Nodal Signaling ◽  
Male Germ Cells ◽  
Embryonic Germ Cells ◽  
Meiotic Inhibitors ◽  
First Time

The mechanisms regulating the entry into meiosis in mammalian germ cells remain incompletely understood. We investigated the involvement of the TGF-β family members in fetal germ cell meiosis initiation. Nodal, a member of the TGF-β family, and its target genes are precociously expressed in embryonic gonads and show sexual dimorphism in favor of the developing testis. Nodal receptor genes, Acvr2a and Acvr2b, Alk4, and Tdgf1/Cripto, were identified in male germ cells. Nodal itself, Tdgf1, and Lefty1 and Lefty2 are targets of Nodal signaling and were all found specifically expressed in male germ cells. To elucidate the role of this signaling pathway, activin-like kinases that mediate TGF-β/Nodal/activin signaling were inhibited in 11.5 d postconception testis in organotypic culture. Activin-like kinases inhibition disrupted normal male germ cell development and induced germ cell entry into meiosis such as that observed in female germ cells at the equivalent stage. Interestingly Stra8, the gatekeeper of the mitotic/meiotic switch, was induced independently of any change of either Cyp26b1 or Fgf9 expression, the two genes currently identified as testicular meiotic inhibitors. On the other hand, recombinant Nodal significantly dampened Stra8 expression and germ cell meiosis in cultured 11.5 d postconception ovaries. Our results allowed us to propose for the first time an autocrine role of Nodal during the development of germ cells and indicate that members of the TGB-β family may reinforce the male fate and prevent meiosis in embryonic germ cells.

STUDIES ON ARTIFICIAL CRYPTORCHIDISM: DEGENERATIVE AND REGENERATIVE CHANGES IN THE GERMINAL EPITHELIUM OF THE RAT TESTIS

1963 ◽  
Vol 27 (2) ◽  
pp. 241-251 ◽  
Author(s):  
E. J. CLEGG
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Initial Phase ◽  
Environmental Temperature ◽  
Degenerative Changes ◽  
Germinal Epithelium ◽  
Seminiferous Tubules ◽  
Cell Degeneration ◽  
Rat Testis ◽  
Germ Cell Degeneration

SUMMARY 1. In the rat bilateral artificial cryptorchidism results in degenerative changes in the seminiferous tubules which are maximal about the 15th day after operation. Up to this stage all germ cells are reduced in number, spermatogonia being least affected and spermatids most. Spermatogonial mitoses and spermatocytial meioses are also inhibited to some extent. 2. Following this initial phase of degeneration there is a partial regeneration, most marked in the case of spermatocytes and total germ cells, which at the 35th day results in the formation of early spermatids. 3. The degree of germ-cell degeneration after 15 days of cryptorchidism is greater than the maximal degeneration after hypophysectomy. It is considered that the increased environmental temperature of the testes may 'block' the action of gonadotrophins on the seminiferous tubules as well as damage the germ cells directly. The occurrence of a certain degree of regeneration may indicate that this 'block' can be overcome to some extent by increased production of pituitary gonadotrophins.

scholarly journals The developing ovary of the South American plains vizcacha, Lagostomus maximus (Mammalia, Rodentia): massive proliferation with no sign of apoptosis-mediated germ cell attrition

Reproduction ◽  
2011 ◽  
Vol 141 (5) ◽  
pp. 633-641 ◽  
Author(s):  
N P Leopardo ◽  
F Jensen ◽  
M A Willis ◽  
M B Espinosa ◽  
A D Vitullo
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Ovarian Tissue ◽  
Tunel Assay ◽  
South American ◽  
Follicular Atresia ◽  
The South ◽  
Cell Degeneration ◽  
Lagostomus Maximus ◽  
Apoptotic Activity

Apoptosis-dependent massive germ cell death is considered a constitutive trait of the developing mammalian ovary that eliminates 65–85% of the germinal tissue depending on the species. After birth and during adult lifetime, apoptotic activity moves from the germ cell proper to the somatic compartment, decimating germ cells through follicular atresia until the oocyte reserve is exhausted. In contrast, the South American rodent Lagostomus maximus shows suppressed apoptosis-dependent follicular atresia in the adult ovary, with continuous folliculogenesis and massive polyovulation, which finally exhausts the oocyte pool. The absence of follicular atresia in adult L. maximus might arise from a failure to move apoptosis from the germinal stratum to the somatic compartment after birth or being a constitutive trait of the ovarian tissue with no massive germ cell degeneration in the developing ovary. We tested these possibilities by analysing oogenesis, expression of germ cell-specific VASA protein, apoptotic proteins BCL2 and BAX, and DNA fragmentation by TUNEL assay in the developing ovary of L. maximus. Immunolabelling for VASA revealed a massive and widespread colonisation of the ovary and proliferation of germ cells organised in nests that disappeared at late development when folliculogenesis began. No sign of germ cell attrition was found at any time point. BCL2 remained positive throughout oogenesis, whereas BAX was slightly detected in early development. TUNEL assay was conspicuously negative throughout the development. These results advocate for an unrestricted proliferation of germ cells, without apoptosis-driven elimination, as a constitutive trait of L. maximus ovary as opposed to what is normally found in the developing mammalian ovary.

zfh-1 is required for germ cell migration and gonadal mesoderm development in Drosophila

Development ◽  
1998 ◽  
Vol 125 (4) ◽  
pp. 655-666 ◽  
Author(s):  
H.T. Broihier ◽  
L.A. Moore ◽  
M. Van Doren ◽  
S. Newman ◽  
R. Lehmann
Keyword(s):  
Cell Migration ◽  
Germ Cell ◽  
Germ Cells ◽  
Ectopic Expression ◽  
Homeodomain Protein ◽  
Mesoderm Development ◽  
Visceral Mesoderm ◽  
Temporal Course ◽  
Germ Cell Migration

In Drosophila as well as many vertebrate systems, germ cells form extraembryonically and migrate into the embryo before navigating toward gonadal mesodermal cells. How the gonadal mesoderm attracts migratory germ cells is not understood in any system. We have taken a genetic approach to identify genes required for germ cell migration in Drosophila. Here we describe the role of zfh-1 in germ cell migration to the gonadal mesoderm. In zfh-1 mutant embryos, the initial association of germ cells and gonadal mesoderm is blocked. Loss of zfh-1 activity disrupts the development of two distinct mesodermal populations: the caudal visceral mesoderm and the gonadal mesoderm. We demonstrate that the caudal visceral mesoderm facilitates the migration of germ cells from the endoderm to the mesoderm. Zfh-1 is also expressed in the gonadal mesoderm throughout the development of this tissue. Ectopic expression of Zfh-1 is sufficient to induce additional gonadal mesodermal cells and to alter the temporal course of gene expression within these cells. Finally, through analysis of a tinman zfh-1 double mutant, we show that zfh-1 acts in conjunction with tinman, another homeodomain protein, in the specification of lateral mesodermal derivatives, including the gonadal mesoderm.

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