Multigenerational and transgenerational effects of endocrine disrupting chemicals: A role for altered epigenetic regulation?

Xin, Frances; Susiarjo, Martha; Bartolomei, Marisa S.

doi:10.1016/j.semcdb.2015.05.008

Cited by 200 publications

(127 citation statements)

References 116 publications

(127 reference statements)

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“…Recently, early life FGF2 has been shown to have epigenetic effects. Epigenetic marks can include DNA methylation, histone post-translational modifications and non-coding RNAs [77]. FGF2 can influence the methylation status of histones and be influenced by histone methylation.…”

Section: Fgf System In Psychiatric Disordersmentioning

confidence: 99%

Dysregulated fibroblast growth factor (FGF) signaling in neurological and psychiatric disorders

Turner

Eren-Koçak

Inui³

et al. 2016

Seminars in Cell & Developmental Biology

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The role of the fibroblast growth factor (FGF) system in brain-related disorders has received considerable attention in recent years. To understand the role of this system in neurological and psychiatric disorders, it is important to identify the specific members of the FGF family that are implicated, their location and the various mechanisms they can be modulated. Each disorder appears to impact specific molecular players in unique anatomical locations, and all of these could conceivably become targets for treatment. In the last several years, the issue of how to target this system directly has become an area of increasing interest. To date, the most promising therapeutics are small molecule inhibitors and antibodies that modulate FGF receptor (FGFR) function. Beyond attempting to modify the primary players affected by a given brain disorder, it may prove useful to target molecules, such as membrane-bound or extracellular proteins that interact with FGF ligands or FGFRs to modulate signaling.

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Section: Fgf System In Psychiatric Disordersmentioning

confidence: 99%

Dysregulated fibroblast growth factor (FGF) signaling in neurological and psychiatric disorders

Turner

Eren-Koçak

Inui³

et al. 2016

Seminars in Cell & Developmental Biology

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“…Unusual modes of inheritance such as PofO and transgenerational epigenetic effects are readily characterized with mouse TGCT models (45,46). For instance, Sl gb/+ heterozygous mutant males that carry a Kitl deletion transmit strong protection to wildtype male offspring (47).…”

Section: Significancementioning

confidence: 99%

Parent-of-origin effects of A1CF and AGO2 on testicular germ-cell tumors, testicular abnormalities, and fertilization bias

Carouge

Blanc

Knoblaugh

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Testicular tumors, the most common cancer in young men, arise from abnormalities in germ cells during fetal development. Unconventional inheritance for testicular germ cell tumor (TGCT) risk both in humans and mice implicates epigenetic mechanisms. Apolipoprotein B mRNA-editing enzyme complex 1 (APOBEC1) cytidine deaminase and Deadend-1, which are involved in C-to-U RNA editing and microRNA-dependent mRNA silencing, respectively, are potent epigenetic modifiers of TGCT susceptibility in the genetically predisposed 129/Sv inbred mouse strain. Here, we show that partial loss of either APOBEC1 complementation factor (A1CF), the RNA-binding cofactor of APOBEC1 in RNA editing, or Argonaute 2 (AGO2), a key factor in the biogenesis of certain noncoding RNAs, modulates risk for TGCTs and testicular abnormalities in both parent-of-origin and conventional genetic manners. In addition, non-Mendelian inheritance was found among progeny of A1cf and Ago2 mutant intercrosses but not in backcrosses and without fetal loss. Together these findings suggest nonrandom union of gametes rather than meiotic drive or preferential lethality. Finally, this survey also suggested that A1CF contributes to long-term reproductive performance. These results directly implicate the RNA-binding proteins A1CF and AGO2 in the epigenetic control of germ-cell fate, urogenital development, and gamete functions.he germline is the only cell lineage that transmits genetic and epigenetic information across generations. Early in mammalian development, primordial germ cells (PGCs) escape a somatic fate to become unipotent precursors of gametes, the highly specialized cells that give rise to the totipotent zygote upon fertilization (1). Various molecular mechanisms regulate pluripotency by modulating gene expression and protein activity throughout development (2). Failure of pluripotency control can lead to infertility, carcinoma in situ, gamete dysfunctions, and unusual modes of inheritance. Carcinoma in situ anomalously express markers of pluripotency and can give rise to testicular germ cell tumors (TGCTs) (3-7). Studying the genetics, epigenetics, and biology of germ cells (GCs) and TGCTs can provide unique insights about GC development, pluripotency control, tumorigenesis, and unconventional inheritance.TGCTs are the third most heritable cancer and are the most common cancers in young men 15-35 y old (8). Genome-wide association studies (GWAS) in humans identified susceptibility loci such as KIT ligand (KITL), Sprouty 4 (SPRY4), Bcl2 antagonist killer (BAK1), Doublesex-and Mab3-related transcription factor (DMRT1), Deleted in azoospermia RNA-binding protein (DAZL), PRDM transcriptional regulator (PRDM14), the telomerase reverse transcriptase TERT, and its cofactor AFT7IP (9-15). Individually and collectively, however, these susceptibility genes account for only a modest portion of inherited risk. Many genes and inherited factors remain to be discovered, their functions in normal development characterized, and the ways that dysfunction leads to TGCTs inve...

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“…The compounds such as bisphenol-A, di-2-ethylhexyl phthalate (DEHP) and dibutyl phthalate, vinclozolin promote epigenetic transgenerational inheritance into subsequent generations [25]. Hence, extensive screening and multi-generation studies are required prior to registration of agrochemicals and before commercialization of pharmaceutical products.…”

Section: Tripathy and Mohantymentioning

confidence: 99%

Mesenchymal Stem Cells: An Innovative Approach in Pharmacokinetics

Tripathy¹,

Mohanty²

2017

Asian J Pharm Clin Res

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Multipotent mesenchymal stem cells (MSCs) are special kind of stem cells which originate from mesenchyme. These cells can be used as an imperative tool to study reproductive toxicity, carcinogenicity, mutagenicity, genotoxicity, and pharmacokinetics. This novel system may reveal toxicantinduced etiology, decipher detailed understanding on molecular mechanisms of toxicants induced pathways and also enumerate the safe dose of an investigational product. Hence, this could ultimately replace, improve or overtake current predictive models in toxicology. The particular review describes the utilization of MSCs in different field of toxicological and pharmacological research.

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Multigenerational and transgenerational effects of endocrine disrupting chemicals: A role for altered epigenetic regulation?

Cited by 200 publications

References 116 publications

Dysregulated fibroblast growth factor (FGF) signaling in neurological and psychiatric disorders

Dysregulated fibroblast growth factor (FGF) signaling in neurological and psychiatric disorders

Parent-of-origin effects of A1CF and AGO2 on testicular germ-cell tumors, testicular abnormalities, and fertilization bias

Mesenchymal Stem Cells: An Innovative Approach in Pharmacokinetics

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