scholarly journals Embryonic Exposure to Bisphenol A Impairs Primordial Germ Cell Migration without Jeopardizing Male Breeding Capacity

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 307 ◽  
Author(s):  
Marta Lombó ◽  
Lidia Getino-Álvarez ◽  
Alexandra Depincé ◽  
Catherine Labbé ◽  
María Herráez
Keyword(s):  
Bisphenol A ◽  
Hormone Receptors ◽  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Morphometric Study ◽  
Embryonic Exposure ◽  
Germ Cell Migration ◽  
Embryonic Life ◽  
And Migration ◽  
Proliferation And Migration

A large amount of chemicals are released to the environment each year. Among them, bisphenol A (BPA) is of utmost concern since it interferes with the reproductive system of wild organisms due to its capacity to bind to hormone receptors. Additionally, BPA epigenotoxic activity is known to affect basic processes during embryonic life. However, its effects on primordial germ cells (PGCs) proliferation and migration, both mechanisms being crucial for gametogenesis, remain unknown. To investigate the effects of BPA on PGCs migration and eventual testicle development, zebrafish embryos were exposed to 100, 2000 and 4000 µg/L BPA during the first 24 h of development. Vasa immunostaining of PGCs revealed that exposure to 2000 and 4000 µg/L BPA impaired their migration to the genital ridge. Two pivotal genes of PGCs migration (cxcr4b and sdf1a) were highly dysregulated in embryos exposed to these doses, whereas DNA methylation and epigenetic marks in PGCs and their surrounding somatic cells were not altered. Once embryos reached adulthood, the morphometric study of their gonads revealed that, despite the reduced number of PGCs which colonized the genital ridges, normal testicles were developed. Although H3K9ac decreased in the sperm from treated fishes, it did not affect the progeny development.

Proliferation and migration of primordial germ cells during compensatory growth in mouse embryos

Development ◽  
1981 ◽  
Vol 64 (1) ◽  
pp. 133-147
Author(s):  
P. P. L. Tam ◽  
M. H. L. Snow
Keyword(s):  
Mitomycin C ◽  
Germ Cells ◽  
Compensatory Growth ◽  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Primitive Streak ◽  
Mouse Embryos ◽  
Newborn Mice ◽  
Embryonic Life ◽  
And Migration

Primitive-streak-stage mouse embryos were treated with Mitomycin C injected intraperitoneally into pregnant females at 6·75–7·0 days post coitum. The newborn mice developed poorly and mortality was high during the suckling period. Many weaned survivors showed impaired fertility and poor breeding performance. Histological examination revealed a paucity of germ cells in the adult gonads. The deficiency was mainly caused by a severe reduction of the primordial germ cell population in early embryonic life, which was not fully compensated for during the compensatory growth phase of the Mitomycin C-treated embryo. Also contributing to such impaired fertility were retarded migration of the primordial germ cells into the genital ridges, poor development of the foetal gonad and secondary loss of the germ cells during gametogenesis in males.

Primordial germ cell migration in Drosophila melanogaster is controlled by somatic tissue

Development ◽  
1994 ◽  
Vol 120 (1) ◽  
pp. 83-89 ◽  
Author(s):  
M.K. Jaglarz ◽  
K.R. Howard
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Characteristic Time ◽  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Somatic Tissue ◽  
Migratory Behavior ◽  
Somatic Tissues ◽  
Germ Cell Migration ◽  
And Migration

In Drosophila, as in many other organisms, primordial germ cells show invasive and migratory behavior moving from their site of origin to the somatic component of the gonad. At a characteristic time in development, the primordial germ cells pass across the primordium of the gut and migrate on its outer surface toward the mesoderm, where they eventually associate with the somatic tissues of the gonad. Here we demonstrate that the exit and migration are specific behaviors of the primordial germ cells and that they are controlled by the somatic tissue of the embryo rather than by a germ cell autonomous clock. Using mutations, we show that these controlling somatic events probably occur in the tissue of the gut primordium itself.

The active migration of Drosophila primordial germ cells

Development ◽  
1995 ◽  
Vol 121 (11) ◽  
pp. 3495-3503 ◽  
Author(s):  
M.K. Jaglarz ◽  
K.R. Howard
Keyword(s):  
Primary Culture ◽  
Germ Cells ◽  
Actin Polymerization ◽  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Cell Polarization ◽  
Germ Cell Migration ◽  
Oriented Movement

We describe our analysis of primordial germ cell migration in Drosophila wild-type and mutant embryos using high resolution microscopy and primary culture in vitro. During migratory events the germ cells form transient interactions with each other and surrounding somatic cells. Both in vivo and in vitro they extend pseudopodia and the accompanying changes in the cytoskeleton suggest that actin polymerization drives these movements. These cellular events occur from the end of the blastoderm stage and are regulated by environmental cues. We show that the vital transepithelial migration allowing exit from the gut primordium and passage into the interior of the embryo is facilitated by changes in the structure of this epithelium. Migrating germ cells extend processes in different directions. This phenomenon also occurs in primary culture where the cells move in an unoriented fashion at substratum concentration-dependent rates. In vivo this migration is oriented leading germ cells to the gonadal mesoderm. We suggest that this guidance involves stabilization of states of an intrinsic cellular oscillator resulting in cell polarization and oriented movement.

Bisphenol A Promotes the Invasive and Metastatic Potential of Ductal Carcinoma In Situ and Protumorigenic Polarization of Macrophages

2019 ◽  
Vol 170 (2) ◽  
pp. 283-295 ◽  
Author(s):  
Hyelim Kim ◽  
Hoe Suk Kim ◽  
Yin Ji Piao ◽  
Woo Kyung Moon
Keyword(s):  
Bisphenol A ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Macrophage Polarization ◽  
Differentially Expressed ◽  
Oral Exposure ◽  
And Migration ◽  
Proliferation And Migration

Abstract Increased cancer risk and immune disorders linked with exposure to environmental endocrine disruptors like bisphenol A (BPA) have been steadily reported. Nevertheless, the impacts of BPA on the breast ductal carcinoma in situ (DCIS) progression and macrophage polarization remain to be elucidated. Here, we analyzed the differentially expressed genes in BPA-exposed DCIS cells and explored BPA effects on DCIS progression and macrophage polarization in vitro and in vivo. Two hundred and ninety-one genes were differentially expressed in 10−8 M BPA-exposed DCIS cells, in which the gene ontology terms of biological processes associated with negative regulation of cell death, cell adhesion, and immune response was enriched. 10−8 M BPA promoted the proliferation and migration of DCIS cells and the migration of macrophages, and upregulated the expression of M1 (NOS2) or M2 markers (Arg-1 and CD206) in macrophages. In coculture system, the migratory capacity of both cells and the expression levels of NOS2, Arg-1, and CD206 in macrophages were significantly enhanced upon 10−8 M BPA. In a DCIS xenograft model, oral exposure to an environmentally human-relevant low dose of 2.5 µg/l BPA for 70 days via drinking water led to an approximately 2-fold promotion in the primary tumor growth rate and a significant enhancement of lymph node metastasis along with increased protumorigenic CD206+ M2 polarization of macrophages. These results demonstrate that BPA acts as an accelerator to promote DCIS progression to invasive breast cancer by affecting DCIS cell proliferation and migration as well macrophage polarization toward a protumorigenic phenotype.

Effects of 2,2',5,5'-tetrachlorobiphenyl (PCB52) on migration of chicken primordial germ cells

2005 ◽  
Vol 17 (5) ◽  
pp. 587 ◽  
Author(s):  
Yixiang Zhang ◽  
Xiumei Jin ◽  
Haitang Han ◽  
Zandong Li
Keyword(s):  
Cell Migration ◽  
Germ Cell ◽  
Germ Cells ◽  
Direct Action ◽  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Initial Stage ◽  
Germ Cell Migration ◽  
Cell Migration And Proliferation ◽  
Migration And Development

Polychlorinated biphenyls cause developmental and physiological anomalies in the reproductive system. This study investigated the effects of 2,2′,5,5′-tetrachlorobiphenyl (PCB52), which can produce oestrogenic effects on the homeostasis of chicken primordial germ cells from the initial stage until completion of their settlement in the gonadal primordium. The blastoderm of chicken embryos was injected with 1 μL PCB52 (10 µmol/L) and oestradiol (100 µmol/L) before incubation, and the number of primordial germ cells was determined during their migration and development. The number of primordial germ cells in germinal crescents in PCB52-treated groups was slightly decreased (P = 0.068), but it was reduced significantly at stages 13–15 and 28–30 (P < 0.01, respectively) compared with controls. No obvious effects on primordial germ cell migration were observed with oestradiol treatments. The present results suggest that the influence of PCB52 on chicken primordial germ cell migration and proliferation may be via its toxic effect, not its oestrogen-mimicking effect, and provide information on the sensitivity of primordial germ cells to the direct action of PCB52.

Mouse primordial germ cells lacking beta1 integrins enter the germline but fail to migrate normally to the gonads

Development ◽  
1999 ◽  
Vol 126 (8) ◽  
pp. 1655-1664 ◽  
Author(s):  
R. Anderson ◽  
R. Fassler ◽  
E. Georges-Labouesse ◽  
R.O. Hynes ◽  
B.L. Bader ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cell Migration ◽  
Germ Cell ◽  
Germ Cells ◽  
Fluorescent Protein ◽  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Integrin Subunit ◽  
Integrin Beta1 ◽  
Germ Cell Migration

Primordial germ cells are the founder cells of the gametes. They are set aside at the initial stages of gastrulation in mammals, become embedded in the hind-gut endoderm, then actively migrate to the sites of gonad formation. The molecular basis of this migration is poorly understood. Here we sought to determine if members of the integrin family of cell surface receptors are required for primordial germ cell migration, as integrins have been implicated in the migration of several other motile cell types. We have established a line of mice which express green fluorescent protein in germline cells that has enabled us to efficiently purify primordial germ cells at different stages by flow cytometry. We have catalogued the spectrum of integrin subunit expression by primordial germ cells during and after migration, using flow cytometry, immunocytochemistry and RT-PCR. Through analysis of integrin beta1(−/−)--&gt;wild-type chimeras, we show that embryonic cells lacking beta1 integrins can enter the germline. However, integrin beta1(−/−) primordial germ cells do not colonize the gonad efficiently. Embryos with targeted deletion of integrin subunit alpha3, alpha6, or alphaV show no major defects in primordial germ cell migration. These results demonstrate a role for beta1-containing integrins in the development of the germline, although an equivalent role for * integrin subunit(s) has yet to be established.

Regulation of zebrafish primordial germ cell migration by attraction towards an intermediate target

Development ◽  
2002 ◽  
Vol 129 (1) ◽  
pp. 25-36
Author(s):  
Gilbert Weidinger ◽  
Uta Wolke ◽  
Marion Köprunner ◽  
Christine Thisse ◽  
Bernard Thisse ◽  
...  
Keyword(s):  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Somatic Cells ◽  
Time Lapse ◽  
Intermediate Target ◽  
Target Time ◽  
Mesoderm Development ◽  
Somatic Tissues ◽  
Germ Cell Migration ◽  
Anterior Trunk

Migration of primordial germ cells (PGCs) from their site of specification towards the developing gonad is controlled by directional cues from somatic tissues. Although in several animals the PGCs are attracted by signals emanating from their final target, the gonadal mesoderm, little is known about the mechanisms that control earlier steps of migration. We provide evidence that a key step of zebrafish PGC migration, in which the PGCs become organized into bilateral clusters in the anterior trunk, is regulated by attraction of PGCs towards an intermediate target. Time-lapse observations of wild-type and mutant embryos reveal that bilateral clusters are formed at early somitogenesis, owing to migration of PGCs towards the clustering position from medial, posterior and anterior regions. Furthermore, PGCs migrate actively relative to their somatic neighbors and they do so as individual cells. Using mutants that exhibit defects in mesoderm development, we show that the ability to form PGC clusters depends on proper differentiation of the somatic cells present at the clustering position. Based on these findings, we propose that these somatic cells produce signals that attract PGCs. Interestingly, fate-mapping shows that these cells do not give rise to the somatic tissues of the gonad, but rather contribute to the formation of the pronephros. Thus, the putative PGC attraction center serves as an intermediate target for PGCs, which later actively migrate towards a more posterior position. This final step of PGC migration is defective in hands off mutants, where the intermediate mesoderm of the presumptive gonadal region is mispatterned. Our results indicate that zebrafish PGCs are guided by attraction towards two signaling centers, one of which may represent the somatic tissues of the gonad.Movies available on-line

scholarly journals Delay in primordial germ cell migration in adamts9 knockout zebrafish

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jonathan J. Carver ◽  
Yuanfa He ◽  
Yong Zhu
Keyword(s):  
Cell Migration ◽  
Germ Cell ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Ring Stage ◽  
C Elegans ◽  
Germ Cell Migration ◽  
A Disintegrin And Metalloproteinase

AbstractAdamts9 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 9) is one of a few metalloproteinases structurally conserved from C. elegans to humans and is indispensable in germ cell migration in invertebrates. However, adamts9′s roles in germ cell migration in vertebrates has not been examined. In the present study, we found zygotic expression of adamts9 started around the germ ring stage and reached peak levels at 3 days post fertilization (dpf) in zebrafish. The migration of primordial germ cells (PGC) was completed within 24 hours (h) in wildtype siblings, while a delay in PGC migration was found at 15 and 24-h post-fertilization (hpf) in the Adamts9 knockout (KO). However, the delayed PGC migration in Adamts9 KO disappeared at 48 hpf. Our study suggests a conserved function of Adamts9 in germ cell migration among invertebrates and vertebrates. In addition, our results also suggest that Adamts9 is not essential for germ cell migration as reported in C. elegans, possibly due to expansion of Adamts family members and compensatory roles from other metalloproteinases in vertebrates. Further studies are required in order to elucidate the functions and mechanisms of metalloproteinases in germ cell migration and gonad formation in vertebrates.

scholarly journals Discrete somatic niches coordinate proliferation and migration of primordial germ cells via Wnt signaling

2016 ◽  
Vol 214 (2) ◽  
pp. 215-229 ◽  
Author(s):  
Andrea V. Cantú ◽  
Svetlana Altshuler-Keylin ◽  
Diana J. Laird
Keyword(s):  
Cell Cycle ◽  
Germ Cell ◽  
Wnt Signaling ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Early Embryo ◽  
Cell Pool ◽  
And Migration ◽  
Selective Mechanism ◽  
Proliferation And Migration

Inheritance depends on the expansion of a small number of primordial germ cells (PGCs) in the early embryo. Proliferation of mammalian PGCs is concurrent with their movement through changing microenvironments; however, mechanisms coordinating these conflicting processes remain unclear. Here, we find that PGC proliferation varies by location rather than embryonic age. Ror2 and Wnt5a mutants with mislocalized PGCs corroborate the microenvironmental regulation of the cell cycle, except in the hindgut, where Wnt5a is highly expressed. Molecular and genetic evidence suggests that Wnt5a acts via Ror2 to suppress β-catenin–dependent Wnt signaling in PGCs and limit their proliferation in specific locations, which we validate by overactivating β-catenin in PGCs. Our results suggest that the balance between expansion and movement of migratory PGCs is fine-tuned in different niches by the opposing β-catenin–dependent and Ror2-mediated pathways through Wnt5a. This could serve as a selective mechanism to favor early and efficient migrators with clonal dominance in the ensuing germ cell pool while penalizing stragglers.

Sign in / Sign up

Export Citation Format

Share Document