scholarly journals Estrogen Receptor β-Mediated Inhibition of Male Germ Cell Line Development in Mice by Endogenous Estrogens during Perinatal Life

Endocrinology ◽  
2004 ◽  
Vol 145 (7) ◽  
pp. 3395-3403 ◽  
Author(s):  
Géraldine Delbès ◽  
Christine Levacher ◽  
Catherine Pairault ◽  
Chrystèle Racine ◽  
Clotilde Duquenne ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Germ Cell ◽  
Experimental Studies ◽  
Cell Lineage ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Testicular Development ◽  
Fetal Life ◽  
Germ Cell Line ◽  
Highly Sensitive ◽  
Labeling Method

Abstract Epidemiological, clinical, and experimental studies have suggested that excessive exposure to estrogens during fetal/neonatal life can lead to reproductive disorders and sperm abnormalities in adulthood. However, it is unknown whether endogenous concentrations of estrogens affect the establishment of the male fetal germ cell lineage. We addressed this question by studying the testicular development of mice in which the estrogen receptor (ER) β or the ERα gene was inactivated. The homozygous inactivation of ERβ (ERβ−/−) increased the number of gonocytes by 50% in 2- and 6-d-old neonates. The numbers of Sertoli and Leydig cells and the level of testicular testosterone production were unaffected, suggesting that estrogens act directly on the gonocytes. The increase in the number of gonocytes did not occur during fetal life but instead occurred just after birth, when gonocytes resumed mitosis and apoptosis. It seems to result from a decrease in the apoptosis rate evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method and cleaved caspase-3 immunohistochemical detection. Last, mice heterozygous for the ERβ gene inactivation behaved similarly to their ERβ−/− littermates in terms of the number of gonocytes, apoptosis, and mitosis, suggesting that these cells are highly sensitive to the binding of estrogens to ERβ. ERα inactivation had no effect on the number of neonatal gonocytes and Sertoli cells. In conclusion, this study provides the first demonstration that endogenous estrogens can physiologically inhibit germ cell growth in the male. This finding may have important implications concerning the potential action of environmental estrogens.

scholarly journals Estrogen effects on fetal and neonatal testicular development

Reproduction ◽  
2006 ◽  
Vol 132 (4) ◽  
pp. 527-538 ◽  
Author(s):  
Géraldine Delbès ◽  
Christine Levacher ◽  
René Habert
Keyword(s):  
Estrogen Receptor ◽  
Developmental Disorders ◽  
Semen Quality ◽  
Estrogenic Activity ◽  
Experimental Studies ◽  
Cell Lineage ◽  
Testicular Development ◽  
Human Populations ◽  
Healthy Children ◽  
Reproductive Disorders

In recent years, evidences have accumulated that exposure to environmental components with estrogenic activity causes reproductive disorders in human populations. Studies conducted over the past 50 years have clearly shown a continual decline in semen quality accompanied by an increase in male reproductive disorders during this period in industrial countries. As healthy gametes are a prerequisite for healthy children, such disorders are a significant problem not only for the current society, but also for future generations. These male reproductive disorders have been attributed to xenobiotics, and particularly to xenoestrogens, which have steadily increased in diversity and concentration in the environment and food. Epidemiological, clinical, and experimental studies have suggested that excessive exposure to estrogens and xenoestrogens during fetal and neonatal development may induce testicular developmental disorders, leading to alterations in the adult male fertility. Recently, we have clearly demonstrated that fetal and neonatal testes are very sensitive to estrogens, as the inactivation of estrogen receptor α increases steroidogenesis and the inactivation of estrogen receptor β enhances development of the germ cell lineage in the male.

scholarly journals Role of Nodal signalling in testis development and initiation of testicular cancer

Reproduction ◽  
2019 ◽  
Vol 158 (2) ◽  
pp. R67-R77 ◽  
Author(s):  
Katrine Harpelunde Poulsen ◽  
Anne Jørgensen
Keyword(s):  
Testicular Cancer ◽  
Germ Cell ◽  
Sertoli Cell ◽  
Cell Function ◽  
Testicular Development ◽  
Fetal Life ◽  
Cell Specification ◽  
Testis Development ◽  
Fetal Testis ◽  
Cancer Pathogenesis

Testicular development from the initially bipotential gonad is a tightly regulated process involving a complex signalling cascade to ensure proper sequential expression of signalling factors and secretion of steroid hormones. Initially, Sertoli cell specification facilitates differentiation of the steroidogenic fetal Leydig cells and establishment of the somatic niche, which is critical in supporting the germ cell population. Impairment of the somatic niche during fetal life may lead to development of male reproductive disorders, including arrest of gonocyte differentiation, which is considered the first step in the testicular cancer pathogenesis. In this review, we will outline the signalling pathways involved in fetal testis development focusing on the Nodal pathway, which has recently been implicated in several aspects of testicular differentiation in both mouse and human studies. Nodal signalling plays important roles in germ cell development, including regulation of pluripotency factor expression, proliferation and survival. Moreover, the Nodal pathway is involved in establishment of the somatic niche, including formation of seminiferous cords, steroidogenesis and Sertoli cell function. In our outline of fetal testis development, important differences between human and mouse models will be highlighted to emphasise that information obtained from mouse studies cannot always be directly translated to humans. Finally, the implications of dysregulated Nodal signalling in development of the testicular cancer precursor, germ cell neoplasia in situ, and testicular dysgenesis will be discussed – none of which arise in rodents, emphasising the importance of human models in the effort to increase our understanding of origin and early development of these disorders.

scholarly journals Cracd Marks the First Wave of Meiosis during Spermatogenesis and Is Mis-Expressed in Azoospermia Mice

2020 ◽  
Vol 8 (3) ◽  
pp. 21
Author(s):  
Paige L. Snider ◽  
Olga Simmons ◽  
Simon J. Conway
Keyword(s):  
Germ Cell ◽  
Gene Activation ◽  
Cell Lineage ◽  
Cell Loss ◽  
Cell Types ◽  
Round Spermatid ◽  
Testicular Development ◽  
Obstructive Azoospermia ◽  
Capping Protein ◽  
Polypyrimidine Tract Binding Protein

Testicular development starts in utero and maturation continues postnatally, requiring a cascade of gene activation and differentiation into different cell types, with each cell type having its own specific function. As we had previously reported that the Capping protein inhibiting regulator of actin (Cracd) gene was expressed in the adult mouse testis, herein we examine when and where the β-catenin associated Cracd is initially expressed during postnatal testis development. Significantly, Cracd mRNA is present in both the immature postnatal and adult testis in round spermatid cells, with highest level of expression occurring during the first wave of meiosis and spermatogenesis. In the juvenile testes, Cracd is initially expressed within the innermost region but as maturation occurs, Cracd mRNA switches to a more peripheral location. Thereafter, Cracd is downregulated to maintenance levels in the haploid male germ cell lineage. As Cracd mRNA was expressed within developing round spermatids, we tested its effectiveness as a biomarker of non-obstructive azoospermia using transgenic knockout mice models. Meaningfully, Cracd expression was absent in Deleted in azoospermia like (Dazl) null testis, which exhibit a dramatic germ cell loss. Moreover, Cracd was abnormally regulated and ectopically mis-expressed in Polypyrimidine tract binding protein-2 (Ptbp2) conditional germ cell restricted knockout testis, which exhibit a block during spermatid differentiation and a reduction in the number of late stage spermatocytes coincident with reduced β-catenin expression. Combined, these data suggest that Cracd is a useful first wave of spermatogenesis biomarker of azoospermia phenotypes, even prior to an overt phenotype being evident.

A study on cell lineage, especially the germ cell line, in embryos of the teleost fish,Barbus conchonius

1992 ◽  
Vol 201 (5) ◽  
pp. 275-283 ◽  
Author(s):  
Petra Gevers ◽  
John Dulos ◽  
Jos G. M. Boogaart ◽  
Lucy P. M. Timmermans
Keyword(s):  
Germ Cell ◽  
Cell Line ◽  
Teleost Fish ◽  
Cell Lineage ◽  
Germ Cell Line

scholarly journals Molecular dissection of the male germ cell lineage identifies putative spermatogonial stem cells in rhesus macaques

2009 ◽  
Vol 24 (7) ◽  
pp. 1704-1716 ◽  
Author(s):  
Brian P. Hermann ◽  
Meena Sukhwani ◽  
David R. Simorangkir ◽  
Tianjiao Chu ◽  
Tony M. Plant ◽  
...  
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Rhesus Macaques ◽  
Cell Lineage ◽  
Spermatogonial Stem Cells ◽  
Male Germ Cell ◽  
Molecular Dissection

Highly Sensitive MALDI Analyses of Glycans by a New Aminoquinoline-Labeling Method Using 3-Aminoquinoline/α-Cyano-4-hydroxycinnamic Acid Liquid Matrix

2011 ◽  
Vol 83 (10) ◽  
pp. 3663-3667 ◽  
Author(s):  
Kaoru Kaneshiro ◽  
Yuko Fukuyama ◽  
Shinichi Iwamoto ◽  
Sadanori Sekiya ◽  
Koichi Tanaka
Keyword(s):  
Hydroxycinnamic Acid ◽  
Liquid Matrix ◽  
Highly Sensitive ◽  
Labeling Method

scholarly journals Ligand–Receptor Interactions Elucidate Sex-Specific Pathways in the Trajectory From Primordial Germ Cells to Gonia During Human Development

2021 ◽  
Vol 9 ◽  
Author(s):  
Arend W. Overeem ◽  
Yolanda W. Chang ◽  
Jeroen Spruit ◽  
Celine M. Roelse ◽  
Susana M. Chuva De Sousa Lopes
Keyword(s):  
Germ Cell ◽  
Signaling Pathways ◽  
Germ Cells ◽  
Tyrosine Kinases ◽  
Intracellular Localization ◽  
Primordial Germ Cells ◽  
Cell Lineage ◽  
Systematic Analysis ◽  
Receptor Interactions

The human germ cell lineage originates from primordial germ cells (PGCs), which are specified at approximately the third week of development. Our understanding of the signaling pathways that control this event has significantly increased in recent years and that has enabled the generation of PGC-like cells (PGCLCs) from pluripotent stem cells in vitro. However, the signaling pathways that drive the transition of PGCs into gonia (prospermatogonia in males or premeiotic oogonia in females) remain unclear, and we are presently unable to mimic this step in vitro in the absence of gonadal tissue. Therefore, we have analyzed single-cell transcriptomics data of human fetal gonads to map the molecular interactions during the sex-specific transition from PGCs to gonia. The CellPhoneDB algorithm was used to identify significant ligand–receptor interactions between germ cells and their sex-specific neighboring gonadal somatic cells, focusing on four major signaling pathways WNT, NOTCH, TGFβ/BMP, and receptor tyrosine kinases (RTK). Subsequently, the expression and intracellular localization of key effectors for these pathways were validated in human fetal gonads by immunostaining. This approach provided a systematic analysis of the signaling environment in developing human gonads and revealed sex-specific signaling pathways during human premeiotic germ cell development. This work serves as a foundation to understand the transition from PGCs to premeiotic oogonia or prospermatogonia and identifies sex-specific signaling pathways that are of interest in the step-by-step reconstitution of human gametogenesis in vitro.

scholarly journals YAP creates epiblast responsiveness to inductive signals for germ cell fate

Development ◽  
2021 ◽  
Author(s):  
Saya Kagiwada ◽  
Shinya Aramaki ◽  
Guangming Wu ◽  
Borami Shin ◽  
Eva Kutejova ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Germ Cell ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Cell Lineage ◽  
Signaling Molecules ◽  
Hippo Signaling ◽  
Epiblast Stem Cells ◽  
Germ Cell Differentiation ◽  
Cell Induction

The germ cell lineage in mammals is induced by the stimulation of pluripotent epiblast cells with signaling molecules. Previous studies have suggested that the germ cell differentiation competence or responsiveness of epiblast cells to signaling molecules is established and maintained in epiblast cells of a specific differentiation state. However, the molecular mechanism underlying this process has not been well defined. Here, using the differentiation model of epiblast stem cells (EpiSCs), we have shown that two defined EpiSC lines have robust germ cell differentiation competence. However, another defined EpiSC line has no competence. By evaluating the molecular basis of EpiSCs with distinct germ cell differentiation competence, we identified YAP/YAP1/YAP65, an intracellular mediator of the Hippo signaling pathway, as a critical mediator for establishing germ cell induction. Strikingly, deletion of YAP severely affected responsiveness to inductive stimuli, leading to a defect in WNT target activation and germ cell differentiation. In conclusion, we propose that the Hippo/YAP signaling pathway creates a potential for germ cell fate induction via mesodermal WNT signaling in pluripotent epiblast cells.

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