scholarly journals Preventing germ cell death by inactivating aryl hydrocarbon receptor (AHR)

2016 ◽  
Vol 7 (2) ◽  
pp. e2116-e2116 ◽  
Author(s):  
P Esakky ◽  
K H Moley
Keyword(s):  
Cell Death ◽  
Germ Cell ◽  
Aryl Hydrocarbon Receptor ◽  
Aryl Hydrocarbon

scholarly journals The Aryl Hydrocarbon Receptor, a Basic Helix-Loop-Helix Transcription Factor of the PAS Gene Family, Is Required for Normal Ovarian Germ Cell Dynamics in the Mouse

Endocrinology ◽  
2000 ◽  
Vol 141 (1) ◽  
pp. 450-453 ◽  
Author(s):  
Rodolfo Robles ◽  
Yutaka Morita ◽  
Koren K. Mann ◽  
Gloria I. Perez ◽  
Shi Yang ◽  
...  
Keyword(s):  
Cell Death ◽  
Transcription Factors ◽  
Germ Cell ◽  
Aryl Hydrocarbon Receptor ◽  
Germ Line ◽  
Wild Type ◽  
Cell Dynamics ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Aryl Hydrocarbon

Abstract The aryl hydrocarbon receptor (AhR), so-designated based on the ability of the protein to bind with and be activated by polycyclic aromatic hydrocarbons (PAH) and related halogenated hydrocarbons, is part of an emerging family of ligand-activated transcriptional regulators that are distinct from the steroid-thyroid hormone receptor superfamily. Once bound by ligand, the AhR interacts with the AhR nuclear translocator (ARNT) protein to form the aryl hydrocarbon receptor complex (AHRC). Both subunits of the AHRC contain sequences corresponding to basic helix-loop-helix domains, a motif that is shared by a number of other dimeric transcription factors. Although the natural ligand(s) for the AhR remains to be elucidated, to date over fifteen genes, including enzymes, growth factors and other transcription factors, have been identified as potential targets for transcriptional regulation by the chemically-activated AHRC. In the ovary, PAH exposure is known to cause destruction of oocytes within immature follicles, implying that one function of the AhR is to mediate cell death signaling in the female germ line. To assess this possibility, we explored AhR expression patterns in the murine ovary, and then determined the impact of AhR-deficiency (gene knockout) on female germ cell dynamics. Immunohistochemical analysis of ovaries of wild-type female mice indicated that AhR protein was abundantly and exclusively expressed in oocytes and granulosa cells of follicles at all stages of development. Histomorphometric analysis of serial ovarian sections revealed a two-fold higher number of primordial follicles in Ahr-null versus wild-type females at day 4 postpartum. This phenotype likely results from a cell-intrinsic death defect in the developing germ line since AhR-deficiency attenuated the magnitude of oocyte apoptosis in fetal ovaries cultured without hormonal support for 72 h. We propose that the AhR, activated by an as yet unknown endogenous ligand(s), serves to regulate the size of the oocyte reserve endowed at birth by affecting germ cell death during female gametogenesis.

Polycyclic Aromatic Hydrocarbons Can Trigger Hepatocyte Release of Extracellular Vesicles by Various Mechanisms of Action Depending on Their Affinity for the Aryl Hydrocarbon Receptor

2019 ◽  
Vol 171 (2) ◽  
pp. 443-462 ◽  
Author(s):  
Nettie van Meteren ◽  
Dominique Lagadic-Gossmann ◽  
Martine Chevanne ◽  
Isabelle Gallais ◽  
Dimitri Gobart ◽  
...  
Keyword(s):  
Cell Death ◽  
Transcription Factor ◽  
Polycyclic Aromatic Hydrocarbons ◽  
Cell Membrane ◽  
Aryl Hydrocarbon Receptor ◽  
Extracellular Vesicles ◽  
Aromatic Hydrocarbons ◽  
Aryl Hydrocarbon ◽  
Polycyclic Aromatic ◽  
Cell Membrane Fluidity

Abstract Extracellular vesicles (EVs) are membrane-enclosed nanostructures released by cells into the extracellular environment. As major actors of physiological intercellular communication, they have been shown to be pathogenic mediators of several liver diseases. Extracellular vesicles also appear to be potential actors of drug-induced liver injury but nothing is known concerning environmental pollutants. We aimed to study the impact of polycyclic aromatic hydrocarbons (PAHs), major contaminants, on hepatocyte-derived EV production, with a special focus on hepatocyte death. Three PAHs were selected, based on their presence in food and their affinity for the aryl hydrocarbon receptor (AhR): benzo[a]pyrene (BP), dibenzo[a,h]anthracene (DBA), and pyrene (PYR). Treatment of primary rat and WIF-B9 hepatocytes by all 3 PAHs increased the release of EVs, mainly comprised of exosomes, in parallel with modifying exosome protein marker expression and inducing apoptosis. Moreover, PAH treatment of rodents for 3 months also led to increased EV levels in plasma. The EV release involved CYP metabolism and the activation of the transcription factor, the AhR, for BP and DBA and another transcription factor, the constitutive androstane receptor, for PYR. Furthermore, all PAHs increased cholesterol levels in EVs but only BP and DBA were able to reduce the cholesterol content of total cell membranes. All cholesterol changes very likely participated in the increase in EV release and cell death. Finally, we studied changes in cell membrane fluidity caused by BP and DBA due to cholesterol depletion. Our data showed increased cell membrane fluidity, which contributed to hepatocyte EV release and cell death.

scholarly journals Association between polymorphisms in the aryl hydrocarbon receptor repressor gene and disseminated testicular germ cell cancer

2013 ◽  
Vol 4 ◽  
Author(s):  
Leon J. S. Brokken ◽  
Yvonne Lundberg-Giwercman ◽  
Ewa Rajpert-De Meyts ◽  
Jakob Eberhard ◽  
Olof Ståhl ◽  
...  
Keyword(s):  
Germ Cell ◽  
Aryl Hydrocarbon Receptor ◽  
Cell Cancer ◽  
Germ Cell Cancer ◽  
Testicular Germ Cell ◽  
Repressor Gene ◽  
Aryl Hydrocarbon ◽  
Testicular Germ Cell Cancer

scholarly journals Activation of the aryl hydrocarbon receptor by a component of cigarette smoke reduces germ cell proliferation in the human fetal ovary

2015 ◽  
Vol 21 (9) ◽  
pp. 753-753 ◽  
Author(s):  
Richard A. Anderson ◽  
Luke McIlwain ◽  
Shiona Coutts ◽  
Hazel L. Kinnell ◽  
Paul A. Fowler ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Germ Cell ◽  
Aryl Hydrocarbon Receptor ◽  
Cigarette Smoke ◽  
Aryl Hydrocarbon ◽  
Fetal Ovary ◽  
Germ Cell Proliferation

scholarly journals The Aryl Hydrocarbon Receptor Relays Metabolic Signals to Promote Cellular Regeneration

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Fanny L. Casado
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Transcription Factor ◽  
Regenerative Medicine ◽  
Aryl Hydrocarbon Receptor ◽  
Signaling Pathways ◽  
Metabolic Efficiency ◽  
Aryl Hydrocarbon ◽  
Cellular Regeneration

While sensing the cell environment, the aryl hydrocarbon receptor (AHR) interacts with different pathways involved in cellular homeostasis. This review summarizes evidence suggesting that cellular regeneration in the context of aging and diseases can be modulated by AHR signaling on stem cells. New insights connect orphaned observations into AHR interactions with critical signaling pathways such as WNT to propose a role of this ligand-activated transcription factor in the modulation of cellular regeneration by altering pathways that nurture cellular expansion such as changes in the metabolic efficiency rather than by directly altering cell cycling, proliferation, or cell death. Targeting the AHR to promote regeneration might prove to be a useful strategy to avoid unbalanced disruptions of homeostasis that may promote disease and also provide biological rationale for potential regenerative medicine approaches.

Activation of aryl hydrocarbon receptor reduces carbendazim-induced cell death

2016 ◽  
Vol 306 ◽  
pp. 86-97 ◽  
Author(s):  
Kuo-Liang Wei ◽  
Fei-Yun Chen ◽  
Chih-Yi Lin ◽  
Guan-Lun Gao ◽  
Wen-Ya Kao ◽  
...  
Keyword(s):  
Cell Death ◽  
Aryl Hydrocarbon Receptor ◽  
Aryl Hydrocarbon

scholarly journals piRNA-associated proteins and retrotransposons are differentially expressed in murine testis and ovary of aryl hydrocarbon receptor deficient mice

Open Biology ◽  
2016 ◽  
Vol 6 (12) ◽  
pp. 160186 ◽  
Author(s):  
Eva M. Rico-Leo ◽  
Nuria Moreno-Marín ◽  
Francisco J. González-Rico ◽  
Eva Barrasa ◽  
Cristina Ortega-Ferrusola ◽  
...  
Keyword(s):  
Transposable Elements ◽  
Germ Cell ◽  
Aryl Hydrocarbon Receptor ◽  
Cell Maturation ◽  
Ovary Development ◽  
Aryl Hydrocarbon ◽  
Sperm Counts ◽  
Associated Proteins ◽  
Pachytene Spermatocytes ◽  
Deficient Mice

Previous studies suggested that the aryl hydrocarbon receptor (AhR) contributes to mice reproduction and fertility. However, the mechanisms involved remain mostly unknown. Retrotransposon silencing by Piwi-interacting RNAs (piRNAs) is essential for germ cell maturation and, remarkably, AhR has been identified as a regulator of murine B1-SINE retrotransposons. Here, using littermate AhR +/+ and AhR −/− mice, we report that AhR regulates the general course of spermatogenesis and oogenesis by a mechanism likely to be associated with piRNA-associated proteins, piRNAs and retrotransposons. piRNA-associated proteins MVH and Miwi are upregulated in leptotene to pachytene spermatocytes with a more precocious timing in AhR −/− than in AhR +/+ testes. piRNAs and transcripts from B1-SINE , LINE-1 and IAP retrotransposons increased at these meiotic stages in AhR-null testes. Moreover, B1-SINE transcripts colocalize with MVH and Miwi in leptonema and pachynema spermatocytes. Unexpectedly, AhR −/− males have increased sperm counts, higher sperm functionality and enhanced fertility than AhR +/+ mice. In contrast, piRNA-associated proteins and B1-SINE and IAP -derived transcripts are reduced in adult AhR −/− ovaries. Accordingly, AhR-null female mice have lower numbers of follicles when compared with AhR +/+ mice. Thus, AhR deficiency differentially affects testis and ovary development possibly by a process involving piRNA-associated proteins, piRNAs and transposable elements.

Sign in / Sign up

Export Citation Format

Share Document