Recent Advances in Tomato Gene Editing.

The use of gene-editing tools, such as zinc finger nucleases, TALEN, and CRISPR/Cas, allows for the modification of physiological, morphological, and other characteristics in a wide range of crops to mitigate the negative effects of stress caused by anthropogenic climate change or biotic stresses. Importantly, these tools have the potential to improve crop resilience and increase yields in response to challenging environmental conditions. This review provides an overview of gene-editing techniques used in plants, focusing on the cultivated tomatoes. Several dozen genes that have been successfully edited with the CRISPR/Cas system were selected for inclusion to illustrate the possibilities of this technology in improving fruit yield and quality, tolerance to pathogens, or responses to drought and soil salinity, among other factors. Examples are also given of how the domestication of wild species can be accelerated using CRISPR/Cas to generate new crops that are better adapted to the new climatic situation or suited to use in indoor agriculture.

Genes involved in auxin biosynthesis, transport and signalling underlie the extreme adventitious root phenotype of the tomato aer mutant.

The use of tomato rootstocks has helped to alleviate the soaring abiotic stresses provoked by the adverse effects of climate change. Lateral and adventitious roots can improve topsoil exploration and nutrient uptake, shoot biomass and resulting overall yield. It is essential to understand the genetic basis of root structure development and how lateral and adventitious roots are produced. Existing mutant lines with specific root phenotypes are an excellent resource to analyse and comprehend the molecular basis of root developmental traits. The tomato aerial roots (aer) mutant exhibits an extreme adventitious rooting phenotype on the primary stem. It is known that this phenotype is associated with restricted polar auxin transport from the juvenile to the more mature stem, but prior to this study, the genetic loci responsible for the aer phenotype were unknown. We used genomic approaches to define the polygenic nature of the aer phenotype and provide evidence that increased expression of specific auxin biosynthesis, transport and signalling genes in different loci causes the initiation of adventitious root primordia in tomato stems. Our results allow the selection of different levels of adventitious rooting using molecular markers, potentially contributing to rootstock breeding strategies in grafted vegetable crops, especially in tomato. In crops vegetatively propagated as cuttings, such as fruit trees and cane fruits, orthologous genes may be useful for the selection of cultivars more amenable to propagation.

Temporal profiling of physiological, histological, and transcriptomic dissection during auxin-induced adventitious root formation in tetraploid Robinia pseudoacacia micro-cuttings.

MAIN CONCLUSION: Optimal levels of indole-3-butyric acid (IBA) applied at the stem base promote adventitious root (AR) initiation and primordia formation, thus promoting the rooting of leafy micro-cuttings of tetraploid Robinia pseudoacacia. Tetraploid Robinia pseudoacacia L. is a widely cultivated tree in most regions of China that has a hard-rooting capability, propagated by stem cuttings. This study utilizes histological, physiological, and transcriptomic approaches to explore how root primordia are induced after indole butyric acid (IBA) treatment of micro-cuttings. IBA application promoted cell divisions in some cells within the vasculature, showing subcellular features associated with adventitious root (AR) founder cells. The anatomical structure explicitly showed that AR initiated from the cambium layer and instigate the inducible development of AR primordia. Meanwhile, the hormone data showed that similar to that of indole-3-acetic acid, the contents of trans-zeatin and abscisic acid peaked at early stages of AR formation and increased gradually in primordia formation across the subsequent stages, suggesting their indispensable roles in AR induction. On the contrary, 24-epibrassinolide roughly maintained at extremely high levels during primordium initiation thoroughly, indicating its presence was involved in cell-specific reorganization during AR development. Furthermore, antioxidant activities transiently increased in the basal region of micro-cuttings and may serve as biochemical indicators for distinct rooting phases, potentially aiding in AR formation. Transcriptomic analysis during the early stages of root formation shows significant downregulation of the abscisic acid and jasmonate signaling pathways, while ethylene and cytokinin signaling seems upregulated. Network analysis of genes involved in carbon metabolism and photosynthesis indicates that the basal region of the micro-cuttings undergoes rapid reprogramming, which results in the breakdown of sugars into pyruvate. This pyruvate is then utilized to fuel the tricarboxylic acid cycle, thereby sustaining growth through aerobic respiration. Collectively, our findings provide a time-course morphophysiological dissection and also suggest the regulatory role of a conserved auxin module in AR development in these species.

Optimization of Callus Induction and Shoot Regeneration from Tomato Cotyledon Explants.

Cultivated tomato (Solanum lycopersicum L.) is one of the most important horticultural crops in the world. The optimization of culture media for callus formation and tissue regeneration of different tomato genotypes presents numerous biotechnological applications. In this work, we have analyzed the effect of different concentrations of zeatin and indole-3-acetic acid on the regeneration of cotyledon explants in tomato cultivars M82 and Micro-Tom. We evaluated regeneration parameters such as the percentage of callus formation and the area of callus formed, as well as the initiation percentage and the number of adventitious shoots. The best hormone combination produced shoot-like structures after 2-3 weeks. We observed the formation of leaf primordia from these structures after about 3-4 weeks. Upon transferring the regenerating micro-stems to a defined growth medium, it was possible to obtain whole plantlets between 4 and 6 weeks. This hormone combination was applied to other genotypes of S. lycopersicum, including commercial varieties and ancestral tomato varieties. Our method is suitable for obtaining many plantlets of different tomato genotypes from cotyledon explants in a very short time, with direct applications for plant transformation, use of gene editing techniques, and vegetative propagation of elite cultivars.

Transcriptomic and hormonal analysis of the roots of maize seedlings grown hydroponically at low temperature.

Prolonged cold stress has a strong effect on plant growth and development, especially in subtropical crops such as maize. Soil temperature limits primary root elongation, mainly during early seedling establishment. However, little is known about how moderate temperature fluctuations affect root growth at the molecular and physiological levels. We have studied root tips of young maize seedlings grown hydroponically at 30 ºC and after a short period (up to 24 h) of moderate cooling (20 ºC). We found that both cell division and cell elongation in the root apical meristem are affected by temperature. Time-course analyses of hormonal and transcriptomic profiles were achieved after temperature reduction from 30 ºC to 20 ºC. Our results highlighted a complex regulation of endogenous pathways leading to adaptive root responses to moderate cooling conditions.

Identification of Transcriptional Networks Involved in De Novo Organ Formation in Tomato Hypocotyl Explants.

Some of the hormone crosstalk and transcription factors (TFs) involved in wound-induced organ regeneration have been extensively studied in the model plant Arabidopsis thaliana. In previous work, we established Solanum lycopersicum "Micro-Tom" explants without the addition of exogenous hormones as a model to investigate wound-induced de novo organ formation. The current working model indicates that cell reprogramming and founder cell activation requires spatial and temporal regulation of auxin-to-cytokinin (CK) gradients in the apical and basal regions of the hypocotyl combined with extensive metabolic reprogramming of some cells in the apical region. In this work, we extended our transcriptomic analysis to identify some of the gene regulatory networks involved in wound-induced organ regeneration in tomato. Our results highlight a functional conservation of key TF modules whose function is conserved during de novo organ formation in plants, which will serve as a valuable resource for future studies.

Unraveling mitochondrial piRNAs in mouse embryonic gonadal cells.

Although mitochondria are widely studied organelles, the recent interest in the role of mitochondrial small noncoding RNAs (sncRNAs), miRNAs, and more recently, piRNAs, is providing new functional perspectives in germ cell development and differentiation. piRNAs (PIWI-interacting RNAs) are single-stranded sncRNAs of mostly about 20-35 nucleotides, generated from the processing of pre-piRNAs. We leverage next-generation sequencing data obtained from mouse primordial germ cells and somatic cells purified from early-differentiating embryonic ovaries and testis from 11.5 to 13.5 days postcoitum. Using bioinformatic tools, we elucidate (i) the origins of piRNAs as transcribed from mitochondrial DNA fragments inserted in the nucleus or from the mitochondrial genome; (ii) their levels of expression; and (iii) their potential roles, as well as their association with genomic regions encoding other sncRNAs (such as tRNAs and rRNAs) and the mitochondrial regulatory region (D-loop). Finally, our results suggest how nucleo-mitochondrial communication, both anterograde and retrograde signaling, may be mediated by mitochondria-associated piRNAs.

Dynamic Hormone Gradients Regulate Wound-Induced de novo Organ Formation in Tomato Hypocotyl Explants.

Plants have a remarkable regenerative capacity, which allows them to survive tissue damage after biotic and abiotic stresses. In this study, we use Solanum lycopersicum 'Micro-Tom' explants as a model to investigate wound-induced de novo organ formation, as these explants can regenerate the missing structures without the exogenous application of plant hormones. Here, we performed simultaneous targeted profiling of 22 phytohormone-related metabolites during de novo organ formation and found that endogenous hormone levels dynamically changed after root and shoot excision, according to region-specific patterns. Our results indicate that a defined temporal window of high auxin-to-cytokinin accumulation in the basal region of the explants was required for adventitious root formation and that was dependent on a concerted regulation of polar auxin transport through the hypocotyl, of local induction of auxin biosynthesis, and of local inhibition of auxin degradation. In the apical region, though, a minimum of auxin-to-cytokinin ratio is established shortly after wounding both by decreasing active auxin levels and by draining auxin via its basipetal transport and internalization. Cross-validation with transcriptomic data highlighted the main hormonal gradients involved in wound-induced de novo organ formation in tomato hypocotyl explants.

piRNA-IPdb: a PIWI-bound piRNAs database to mining NGS sncRNA data and beyond.

BACKGROUND: PIWI-interacting RNAs (piRNAs) are an abundant single-stranded type of small non-coding RNAs (sncRNAs), which initially were discovered in gonadal cells, with a role as defenders of genomic integrity in the germline, acting against the transposable elements. With a regular size range of 21-35 nt, piRNAs are associated with a PIWI-clade of Argonaute family proteins. The most widely accepted mechanisms of biogenesis for piRNAs involve the transcription of longer precursors of RNAs to be processed, by complexes of proteins, to functional size, preferentially accommodating uridine residues at the 5' end and 3' methylation to increase the stability of these molecules. piRNAs have also been detected in somatic cells, with diverse potential functions, indicating their high plasticity and pleiotropic activity. Discovered about two decades ago, piRNAs are a large and versatile type of sncRNA and that remain insufficiently identified and analyzed, through next-generation sequencing (NGS), to evaluate their processing, functions, and biogenesis in different cell types and during development. piRNAs' distinction from other sncRNAs has led to controversial results and interpretation difficulties when using existing databases because of the heterogeneity of the criteria used in making the distinction. DESCRIPTION: We present "piRNA-IPdb", a database based uniquely on datasets obtaining after the defining characteristic of piRNAs: those small RNAs bound to PIWI proteins. We selected and analyzed sequences from piRBase that exclusively cover the binding to PIWI. We pooled a total of 18,821,815 sequences from RNA-seq after immunoprecipitation that included the binding to any of the mouse PIWI proteins (MILI, MIWI, or MIWI2). CONCLUSIONS: In summary, we present the characteristics and potential use of piRNA-IPdb database for the analysis of bona fide piRNAs.

Tissue-Specific Metabolic Reprogramming during Wound-Induced Organ Formation in Tomato Hypocotyl Explants.

Plants have remarkable regenerative capacity, which allows them to survive tissue damage after exposure to biotic and abiotic stresses. Some of the key transcription factors and hormone crosstalk mechanisms involved in wound-induced organ regeneration have been extensively studied in the model plant Arabidopsis thaliana. However, little is known about the role of metabolism in wound-induced organ formation. Here, we performed detailed transcriptome analysis and used a targeted metabolomics approach to study de novo organ formation in tomato hypocotyl explants and found tissue-specific metabolic differences and divergent developmental pathways. Our results indicate that successful regeneration in the apical region of the hypocotyl depends on a specific metabolic switch involving the upregulation of photorespiratory pathway components and the differential regulation of photosynthesis-related gene expression and gluconeogenesis pathway activation. These findings provide a useful resource for further investigation of the molecular mechanisms involved in wound-induced organ formation in crop species such as tomato.

Diversification of piRNAs expressed in PGCs and somatic cells during embryonic gonadal development.

piRNAs are small non-coding RNAs known to play a main role in defence against transposable elements in germ cells. However, other potential functions, such as biogenesis and differences in somatic and germline expression of these regulatory elements, are not yet fully unravelled. Here, we analysed a variety of piRNA sequences detected in mouse male and female primordial germ cells (PGCs) and gonadal somatic cells at crucial stages during embryonic differentiation of germ cells (11.5-13.5 days post-coitum). NGS of sncRNA and bioinformatic characterization of piRNAs from PGCs and somatic cells, in addition to piRNAs associated with TEs, indicated functional diversification in both cell types. Differences in the proportion of the diverse types of piRNAs are detected between somatic and germline during development. However, the global diversified patterns of piRNA expression are mainly shared between germ and somatic cells, we identified piRNAs related with molecules involved in ribosome components and translation pathway, including piRNAs derived from rRNA (34%), tRNA (10%) and snoRNA (8%). piRNAs from both tRNA and snoRNA are mainly derived from 3' and 5' end regions. These connections between piRNAs and rRNAs, tRNAs or snoRNAs suggest important functions of specialized piRNAs in translation regulation during this window of gonadal development.

Combined proteomic and miRNome analyses of mouse testis exposed to an endocrine disruptors chemicals mixture reveals altered toxicological pathways involved in male infertility.

The increase in male idiopathic infertility has been associated with daily exposure to endocrine disruptors chemicals (EDCs). Nevertheless, the mechanisms of action in relation to dysregulating proteins and regulatory microRNAs are unknown. We combined proteomic and miRNome analyses of mouse testis chronically exposed to low doses of a define mixture of EDCs [phthalates: bis(2-ethylhexyl), dibutyl and benzyl-butyl; 4-nonylphenol and 4-tert-octylphenol], administered in the drinking water from conception until adulthood (post-natal Day 60/75) and compared them with no-exposed control mice. We analysed fertility parameters and global changes in the patterns of mice testis proteome by 2D electrophoresis/mass spectrometry, along with bioinformatic analyses of dysregulated microRNAs, and their association with published data in human infertile patients. We detected a decrease in the potential fertility of exposed mice associated with changes in the expression of 18 proteins (10 up-regulated, 8 down-regulated). Functional analysis showed that 89% were involved in cell death. Furthermore, we found a group of 23 microRNAs/isomiRs (down-regulated) correlated with six of the up-regulated target proteins (DIABLO, PGAM1, RTRAF, EIF4E, IVD and CNDP2). Regarding this, PGAM1 up-regulation was validated by Western blot and mainly detected in Sertoli cells. Some of these microRNA/protein dysregulations were reported in human testis with spermatogenic failure. Overall, a chronic exposure to EDCs mixture in human males could potentially lead to spermatogenic failure through changes in microRNA expression, which could post-transcriptionally dysregulate mRNA targets that encode proteins participating in cell death in testicular cells. Finally, these microRNA/protein dysregulations need to be validated with other EDCs mixtures and concentrations.

A phylogenetic approach to the Philippines endemic centipedes of the genus Scolopendra Linnaeus, 1758 (Scolopendromorpha, Scolopendridae), with the description of a new species.

The genus Scolopendra Linnaeus, 1758 is represented in the Philippines' fauna by five species, two of which are endemic. Mitochondrial DNA sequences of gene cytochrome c oxidase subunit I (COI) were obtained from six Scolopendra specimens belonging to two endemic species and a new one, described here as Scolopendra paradoxa Doménech sp. nov. These sequences were analyzed together with another forty-one sequences from GenBank, including additional species of Scolopendra and a few representatives of other Scolopendridae genera. Phylogenetic trees inferred from the COI analysis using maximum likelihood and neighbor joining showed the three Philippines Scolopendra endemic species as a polyphyletic group coherent with their respective morphologies, although the position of S. spinosissima Kraepelin, 1903 varied within the obtained trees. Species delimitation based on standard external morphological characters was also concordant with the observed genetic distances, monophyly and node support, confirming S. subcrustalis Kronmüller, 2009 and S. paradoxa sp. nov. as separate species also at the molecular level, while only the position of S. spinosissima could not be properly established with any of the statistical methods used. In addition, the male genitalia of the three studied species were found to lack gonopods and a penis. Remarks on the ultimate legs prefemoral spinous formula of S. spinosissima plus a key to the species of the genus Scolopendra in the Philippines are provided.

The landscape of mitochondrial small non-coding RNAs in the PGCs of male mice, spermatogonia, gametes and in zygotes.

BACKGROUND: Mitochondria are organelles that fulfill a fundamental role in cell bioenergetics, as well as in other processes like cell signaling and death. Small non-coding RNAs (sncRNA) are now being considered as pivotal post-transcriptional regulators, widening the landscape of their diversity and functions. In mammalian cells, small RNAs encoded by the mitochondrial genome, mitosRNAs were discovered recently, although their biological role remains uncertain. RESULTS: Here, using specific bioinformatics analyses, we have defined the diversity of mitosRNAs present in early differentiated germ cells of male mice (PGCs and spermatogonia), and in the gametes of both sexes and in zygotes. We found strong transcription of mitosRNAs relative to the size of the mtDNA, and classifying these mitosRNAs into different functional sncRNA groups highlighted the predominance of Piwi-interacting RNAs (piRNAs) relative to the other types of mitosRNAs. Mito-piRNAs were more abundant in oocytes and zygotes, where mitochondria fulfill key roles in fecundation process. Functional analysis of some particular mito-piRNAs (mito-piR-7,456,245), also expressed in 3T3-L1 cells, was assessed after exposure to RNA antagonists. CONCLUSIONS: As far as we are aware, this is the first integrated analysis of sncRNAs encoded by mtDNA in germ cells and zygotes. The data obtained suggesting that mitosRNAs fulfill key roles in gamete differentiation and fertilization.

An integrative piRNA analysis of mouse gametes and zygotes reveals new potential origins and gene regulatory roles.

Piwi-interacting RNAs (piRNAs) are a subclass of the small non-coding RNAs (sncRNAs). Their main reported function was to exert control over transposable elements (TEs) in mammalian germline. In this study undertaking a deeper bioinformatics analysis of piRNAs present in mouse oocytes, sperm cells and zygotes, we first elaborated a new piRNA database based on sequences identified as piRNAs by immunoprecipitation with PIWI proteins. Our bioinformatics analysis revealed that, at least in gametes and zygotes, piRNAs could encompass multifunctional cell-dependent regulatory molecules. Indeed, genome analysis of the piRNA mapping density (reads/kb) evidenced in all samples an enrichment of intron-derived piRNAs. Further, piRNA population was classified into sequences not associated to TEs or repeats (NRapiRNAs) and associated to repetitive genome elements (RapiRNAs). In oocytes most of the NRapiRNAs mapped to the 5'UTRs of coding mRNAs, while higher proportion of NRapiRNAs was detected in sperm cells associated to the 3'UTRs of mRNAs. This piRNA complementarity to mRNA UTRs suggests key post-transcriptional regulatory roles over mRNAs such as those encoding MHC genes. In addition, a striking association of RapiRNA with long non-coding RNAs (lncRNAs) was identified. piRNAs associated with relevant lncRNAs such as: Rab26os and GAS5 and key mRNAs, were particularly assessed.

MicroRNA dynamics at the onset of primordial germ and somatic cell sex differentiation during mouse embryonic gonad development.

In mammals, commitment and specification of germ cell lines involves complex programs that include sex differentiation, control of proliferation, and meiotic initiation. Regulation of these processes is genetically controlled by fine-tuned mechanisms of gene regulation in which microRNAs (miRNAs) are involved. We have characterized, by small-RNA-seq and bioinformatics analyses, the miRNA expression patterns of male and female mouse primordial germ cells (PGCs) and gonadal somatic cells at embryonic stages E11.5, E12.5, and E13.5. Differential expression analyses revealed differences in the regulation of key miRNA clusters such as miR-199-214, miR-182-183-96, and miR-34c-5p, whose targets have defined roles during gonadal sexual determination in both germ and somatic cells. Extensive analyses of miRNA sequences revealed an increase in noncanonical isoforms on PGCs at E12.5 and dramatic changes of 3' isomiR expression and 3' nontemplate nucleotide additions in female PGCs at E13.5. Additionally, RT-qPCR analyses of genes encoding proteins involved in miRNA biogenesis and 3' nucleotide addition uncovered sexually and developmentally specific expression, characterized by the decay of Drosha, Dgcr8, and Xpo5 expression along gonadal development. These results demonstrate that miRNAs, their isomiRs, and miRNA machinery are differentially regulated and participate actively in gonadal sexual differentiation in both PGCs and gonadal somatic cells.

Editor's Highlight: Differential Effects of Exposure to Single Versus a Mixture of Endocrine-Disrupting Chemicals on Steroidogenesis Pathway in Mouse Testes.

Endocrine-disrupting chemicals (EDCs) generate reproductive dysfunctions affecting the biosynthesis of steroid hormones and genes of the steroidogenic pathway. EDCs effects are mainly reported as a result of exposure to single compounds. However, humans are environmentally exposed to a mixture of EDCs. Herein, we assess chronic exposure to single alkylphenols and phthalates versus a mixture in mouse testes histology and steroidogenesis. Pregnant mice were exposed through drinking water to: 0.3 mg/kg-body weight (BW)/d of each phthalate (bis (2-ethylhexyl) phthalate, dibutyl phthalate, benzyl butyl phthalate), 0.05 mg/kg-BW/d of each alkylphenol (4-nonylphenol, 4-tert-octylphenol), or their mixture, covering from 0.5 postcoital day to weaning, continuing in the male offspring each exposure until adulthood (60-days old). Body and relative testis weight were increased in mixture-exposed mice along with histological alterations. Intratesticular testosterone (T) changed only in mice exposed to DBP, whereas estradiol (E2) levels were altered in all groups (except benzyl butyl phthalate). mRNA levels of genes encoding hormones of the steroid pathway (Cyp11a1, Hsd3b1, Cyp17a1, and Cyp19a1), cholesterol transporters (Star), and transcriptional factors (Sp1) showed that mice exposed to single or mixed compounds had alterations in at least 2 transcripts. However, none of the different types of exposure induced changes in all transcripts. In addition, changes at the mRNA or protein levels with single compounds were not always the same as those with a mixture. In conclusion, the effects of a chronic exposure to a mixture of EDCs on the expression of genes and proteins of the steroidogenic pathway and hormonal status were different from those exposed to single EDC.

Chronic low-dose exposure to a mixture of environmental endocrine disruptors induces microRNAs/isomiRs deregulation in mouse concomitant with intratesticular estradiol reduction.

Humans are environmentally exposed not only to single endocrine-disrupting chemicals (EDCs) but to mixtures that affect their reproductive health. In reproductive tissues, microRNAs (miRNAs) are emerging as key targets of EDCs. Here, we analysed changes in the testis "miRNome" (and their biogenesis mechanism) in chronically exposed adult mice to a cocktail of five EDCs containing 0.3 mg/kg-body weight (BW)/day of each phthalate (DEHP, DBP, BBP) and 0.05 mg/kg-BW/day of each alkylphenol (NP, OP), from conception to adulthood. The testis "miRNome" was characterised using next-generation sequencing (NGS). Expression levels of genes involved in miRNA biogenesis were measured by RT-qPCR, as well as several physiological and cytological parameters. We found two up-regulated, and eight down-regulated miRNAs and thirty-six differentially expressed isomiRs along with an over-expression of Drosha, Adar and Zcchc11. A significant decrease of intratesticular estradiol but not testosterone was detected. Functional analysis showed altered spermatogenesis, germ cell apoptosis and negative correlation of miR-18a-5p with Nr1h2 involved in the deregulation of the steroidogenesis pathway. Here, we present the first association between miRNA/isomiRs deregulation, their mechanisms of biogenesis and histopathological and hormonal alterations in testes of adult mice exposed to a mixture of low-dose EDCs, which can play a role in male infertility.

Detection and Characterization of Small Noncoding RNAs in Mouse Gametes and Embryos Prior to Zygotic Genome Activation.

Small noncoding RNAs (ncRNAs) are regulatory elements of gene expression in all cell types and tissues. An ever-increasing number of studies have implicated ncRNAs in differentiation and developmental processes. In mammals, as a consequence of fertilization, the content of ncRNAs in the zygote is mostly the result of the maternal material included on oocytes and the potential sperm-borne paternal contributions. The genetic identity program of any individual is the reprogramming of each parental contribution to the zygotic genome activation. In mouse, this activation occurs at 2-cell stage. In this program of early development the small ncRNAs can play important roles. Here, we describe protocols for collection of oocytes, spermatozoa, and zygotes in mouse, followed by RNA purification to analyze the different types of small ncRNA by next-generation sequencing approaches (NGS). Bioinformatics protocols also describe the methodology able to characterize microRNAs (miRNAs) as the most well-known and widespread regulatory small ncRNA. The comparative analysis allows identifying the changes and background previous to zygotic genome activation.

Endocrine disrupters, microRNAs, and primordial germ cells: a dangerous cocktail.

Endocrine-disrupting chemicals (EDCs) are environmental pollutants that may change the homeostasis of the endocrine system, altering the differentiation of germ cells with consequences for reproduction. In mammals, germ cell differentiation begins with primordial germ cells (PGCs) during embryogenesis. Primordial germ cell development and gametogenesis are genetically regulated processes, in which the posttranscriptional gene regulation could be mediated by small noncoding RNAs (sncRNAs) such as microRNAs (miRNAs). Here, we review the deleterious effects of exposure during fetal life to EDCs mediated by deregulation of ncRNAs, and specifically miRNAs on PGC differentiation. Moreover, the environmental stress induced by exposure to some EDCs during the embryonic window of development could trigger reproductive dysfunctions transgenerationally transmitted by epigenetic mechanisms with the involvement of miRNAs expressed in germ line cells.