'; ?> geneimprint : Hot off the Press http://www.geneimprint.com/site/hot-off-the-press Daily listing of the most recent articles in epigenetics and imprinting, collected from the PubMed database. en-us Fri, 31 Mar 2023 09:24:05 EDT Fri, 31 Mar 2023 09:24:05 EDT jirtle@radonc.duke.edu james001@jirtle.com Brain-derived neurotrophic factor (BDNF) epigenomic modifications and brain-related phenotypes in humans: A systematic review. Treble-Barna A, Heinsberg LW, Stec Z, Breazeale S, Davis TS, Kesbhat AA, Chattopadhyay A, VonVille HM, Ketchum AM, Yeates KO, Kochanek PM, Weeks DE, Conley YP
Neurosci Biobehav Rev (Apr 2023)

Epigenomic modifications of the brain-derived neurotrophic factor (BDNF) gene have been postulated to underlie the pathogenesis of neurodevelopmental, psychiatric, and neurological conditions. This systematic review summarizes current evidence investigating the association of BDNF epigenomic modifications (DNA methylation, non-coding RNA, histone modifications) with brain-related phenotypes in humans. A novel contribution is our creation of an open access web-based application, the BDNF DNA Methylation Map, to interactively visualize specific positions of CpG sites investigated across all studies for which relevant data were available. Our literature search of four databases through September 27, 2021 returned 1701 articles, of which 153 met inclusion criteria. Our review revealed exceptional heterogeneity in methodological approaches, hindering the identification of clear patterns of robust and/or replicated results. We summarize key findings and provide recommendations for future epigenomic research. The existing literature appears to remain in its infancy and requires additional rigorous research to fulfill its potential to explain BDNF-linked risk for brain-related conditions and improve our understanding of the molecular mechanisms underlying their pathogenesis.]]> Wed, 31 Dec 1969 19:00:00 EST 4D epigenomics: deciphering the coupling between genome folding and epigenomic regulation with biophysical modeling. Abdulla AZ, Salari H, Tortora MMC, Vaillant C, Jost D
Curr Opin Genet Dev (Apr 2023)

Recent experimental observations suggest a strong coupling between the 3D nuclear chromosome organization and epigenomics. However, the mechanistic and functional bases of such interplay remain elusive. In this review, we describe how biophysical modeling has been instrumental in characterizing how genome folding may impact the formation of epigenomic domains and, conversely, how epigenomic marks may affect chromosome conformation. Finally, we discuss how this mutual feedback loop between chromatin organization and epigenome regulation, via the formation of physicochemical nanoreactors, may represent a key functional role of 3D compartmentalization in the assembly and maintenance of stable - but yet plastic - epigenomic landscapes.]]> Wed, 31 Dec 1969 19:00:00 EST Comparison between indicine and taurine cattle DNA methylation reveals epigenetic variation associated to differences in morphological adaptive traits. Capra E, Lazzari B, Milanesi M, Nogueira GP, Garcia JF, Utsunomiya YT, Ajmone-Marsan P, Stella A
Epigenetics (Dec 2023)

Indicine and taurine subspecies present distinct morphological traits as a consequence of environmental adaptation and artificial selection. Although the two subspecies have been characterized and compared at genome-wide level and at specific loci, their epigenetic diversity has not yet been explored. In this work, Reduced Representation Bisulphite Sequencing (RRBS) profiling of the taurine Angus (A) and indicine Nellore (N) cattle breeds was applied to identify methylation differences between the two subspecies. Genotyping by sequencing (GBS) of the same animals was performed to detect single nucleotide polymorphisms (SNPs) at cytosines in CpG dinucleotides and remove them from the differential methylation analysis. A total of 660,845 methylated cytosines were identified within the CpG context (CpGs) across the 10 animals sequenced (5 N and 5 A). A total of 25,765 of these were differentially methylated (DMCs). Most DMCs clustered in CpG stretches nearby genes involved in cellular and anatomical structure morphogenesis. Also, sequences flanking DMC were enriched in SNPs compared to all other CpGs, either methylated or unmethylated in the two subspecies. Our data suggest a contribution of epigenetics to the regulation and divergence of anatomical morphogenesis in the two subspecies relevant for cattle evolution and sub-species differentiation and adaptation.]]> Wed, 31 Dec 1969 19:00:00 EST Investigation of a pervasive immune, cardiac, and behavioral phenotype in Beckwith-Wiedemann syndrome: A case report. McElroy TD, Duffy KA, Hathaway ER, Byrne ME, Kalish JM
Am J Med Genet A (Apr 2023)

Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder caused by genetic and epigenetic changes in the chromosome 11p15 region. The syndrome is characterized by a wide range of features including macrosomia, lateralized overgrowth, abdominal wall defects, and hypoglycemia. BWS presentation is variable across the entire patient population, but certain areas including immunology, cardiology, and behavioral differences are not well characterized. We present a case of a male patient with BWS due to the most common cause of BWS, loss of methylation at imprinting center 2 with a variable phenotype, including classical features (macrosomia, macroglossia, omphalocele, placentomegaly and mild lateralized overgrowth) in addition to uncommon features (immune deficiency, developmental delays, and pulmonary stenosis) not typically seen in BWS. This study defines a patient's clinical presentation and course and highlights the need to consider atypical organ systems in BWS as either an expansion of the phenotype or co-existing conditions to develop personalized care models.]]> Wed, 31 Dec 1969 19:00:00 EST Uncertainty quantification of reference-based cellular deconvolution algorithms. Vellame DS, Shireby G, MacCalman A, Dempster EL, Burrage J, Gorrie-Stone T, Schalkwyk LS, Mill J, Hannon E
Epigenetics (Dec 2023)

The majority of epigenetic epidemiology studies to date have generated genome-wide profiles from bulk tissues (e.g., whole blood) however these are vulnerable to confounding from variation in cellular composition. Proxies for cellular composition can be mathematically derived from the bulk tissue profiles using a deconvolution algorithm; however, there is no method to assess the validity of these estimates for a dataset where the true cellular proportions are unknown. In this study, we describe, validate and characterize a sample level accuracy metric for derived cellular heterogeneity variables. The CETYGO score captures the deviation between a sample's DNA methylation profile and its expected profile given the estimated cellular proportions and cell type reference profiles. We demonstrate that the CETYGO score consistently distinguishes inaccurate and incomplete deconvolutions when applied to reconstructed whole blood profiles. By applying our novel metric to >6,300 empirical whole blood profiles, we find that estimating accurate cellular composition is influenced by both technical and biological variation. In particular, we show that when using a common reference panel for whole blood, less accurate estimates are generated for females, neonates, older individuals and smokers. Our results highlight the utility of a metric to assess the accuracy of cellular deconvolution, and describe how it can enhance studies of DNA methylation that are reliant on statistical proxies for cellular heterogeneity. To facilitate incorporating our methodology into existing pipelines, we have made it freely available as an R package (https://github.com/ds420/CETYGO).]]> Wed, 31 Dec 1969 19:00:00 EST Lactylation: novel epigenetic regulatory and therapeutic opportunities. Fan H, Yang F, Xiao Z, Luo H, Chen H, Chen Z, Liu Q, Xiao Y
Am J Physiol Endocrinol Metab (Apr 2023)

Lactate, which is an end product of glycolysis, has traditionally been considered a metabolic waste. However, numerous studies have demonstrated that lactate serves metabolic and nonmetabolic functions in physiological processes and multiple diseases. Cancer and pulmonary arterial hypertension have been shown to undergo metabolic reprogramming, which is accompanied by increased lactate production. Metabolic reprogramming and epigenetic modifications have been extensively linked; furthermore, posttranslational modifications of histones caused by metabolites play a vital role in epigenetic alterations. In this paper, we reviewed recent research on lactate-induced histone modifications and provided a new vision about the metabolic effect of glycolysis. Based on our review, the cross talk between the metabolome and epigenome induced by glycolysis may indicate novel epigenetic regulatory and therapeutic opportunities. There is a magnificent progress in the interaction between metabolomics and epigenomics in recent decades, but many questions still remained to be investigated. Lactylation is found in different pathophysiological states and leads to diverse biological effects; however, only a few mechanisms of lactylation have been illustrated. Further research on lactylation would provide us with a better understanding of the cross talk between metabolomics and epigenomics.]]> Wed, 31 Dec 1969 19:00:00 EST RAS and PP2A activities converge on epigenetic gene regulation. Aakula A, Sharma M, Tabaro F, Nätkin R, Kamila J, Honkanen H, Schapira M, Arrowsmith C, Nykter M, Westermarck J
Life Sci Alliance (May 2023)

RAS-mediated human cell transformation requires inhibition of the tumor suppressor protein phosphatase 2A (PP2A). However, the phosphoprotein targets and cellular processes in which RAS and PP2A activities converge in human cancers have not been systematically analyzed. Here, we discover that phosphosites co-regulated by RAS and PP2A are enriched on proteins involved in epigenetic gene regulation. As examples, RAS and PP2A co-regulate the same phosphorylation sites on HDAC1/2, KDM1A, MTA1/2, RNF168, and TP53BP1. We validate RAS- and PP2A-elicited regulation of HDAC1/2 chromatin recruitment, of RNF168-TP53BP1 interaction, and of gene expression. Consistent with their known synergistic effects in cancer, RAS activation and PP2A inhibition resulted in epigenetic reporter derepression and activation of oncogenic transcription. Transcriptional derepression by PP2A inhibition was associated with an increase in euchromatin and a decrease in global DNA methylation. Collectively, the results indicate that epigenetic protein complexes constitute a significant point of convergence for RAS hyperactivity and PP2A inhibition in cancer. Furthermore, the work provides an important resource for future studies focusing on phosphoregulation of epigenetic gene regulation in cancer and in other RAS/PP2A-regulated cellular processes.]]> Wed, 31 Dec 1969 19:00:00 EST Genomic, Transcriptomic, and Proteomic Depiction of Induced Pluripotent Stem Cells-Derived Smooth Muscle Cells As Emerging Cellular Models for Arterial Diseases. Liu L, Jouve C, Henry J, Berrandou TE, Hulot JS, Georges A, Bouatia-Naji N
Hypertension (Apr 2023)

Vascular smooth muscle cells (SMCs) plasticity is a central mechanism in cardiovascular health and disease. We aimed at providing cellular phenotyping, epigenomic and proteomic depiction of SMCs derived from induced pluripotent stem cells and evaluating their potential as cellular models in the context of complex diseases.]]> Wed, 31 Dec 1969 19:00:00 EST Acute Transcriptomic and Epigenetic Alterations at T12 After Rat T10 Spinal Cord Contusive Injury. Xie J, Herr S, Ma D, Wu S, Zhao H, Sun S, Ma Z, Chan MY, Li K, Yang Y, Huang F, Shi R, Yuan C
Mol Neurobiol (May 2023)

Spinal cord injury is a severely debilitating condition affecting a significant population in the USA. Spinal cord injury patients often have increased risk of developing persistent neuropathic pain and other neurodegenerative conditions beyond the primary lesion center later in their life. The molecular mechanism conferring to the "latent" damages at distal tissues, however, remains elusive. Here, we studied molecular changes conferring abnormal functionality at distal spinal cord (T12) beyond the lesion center (T10) by combining next-generation sequencing (RNA- and bisulfite sequencing), super-resolution microscopy, and immunofluorescence staining at 7 days post injury. We observed significant transcriptomic changes primarily enriched in neuroinflammation and synaptogenesis associated pathways. Transcription factors (TFs) that regulate neurogenesis and neuron plasticity, including Egr1, Klf4, and Myc, are significantly upregulated. Along with global changes in chromatin arrangements and DNA methylation, including 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), bisulfite sequencing further reveals the involvement of DNA methylation changes in regulating cytokine, growth factor, and ion channel expression. Collectively, our results pave the way towards understanding transcriptomic and epigenomic mechanism in conferring long-term disease risks at distal tissues away from the primary lesion center and shed light on potential molecular targets that govern the regulatory mechanism at distal spinal cord tissues.]]> Wed, 31 Dec 1969 19:00:00 EST A case of KAT6A syndrome with a newly discovered mutation in the gene, mainly manifested as bone marrow failure syndrome. Ai Q, Jiang L, Chen Y, Yao X, Yin J, Chen S
Hematology (Dec 2023)

The clinical and genetic characteristics of a child with inherited bone marrow failure syndrome as prominent clinical manifestations and special facial features were analyzed, and the etiology and mechanism were explored in, combination with clinical practice. Blood samples and clinical information were collected separately from the proband and their biological parents. The pathogenic variant was verified using next-generation sequencing technology screening, and the candidate variable sites were confirmed by using Sanger sequencing among all members of the family. A heterozygous nonsense mutation in exon 17 of (NM_006766), c.4177G > T (p.E1393*) predicted to cause truncation within the acidic domain of the protein was identified. Pedigree analysis did not reveal any variation in this locus between the proband's father and mother. No report of this pathogenic variant was found in a literature search of domestic and foreign databases, indicating that it is a newly discovered mutation. According to the guidelines of the American College of Medical Genetics, the variation was preliminarily determined to be a pathogenic. The newly discovered heterozygous mutation in may be the cause of the disease in this child. Additionally, inherited bone marrow failure syndrome is a prominent manifestation. This study not only provides us with an in-depth understanding of this rare syndrome but also deepens our understanding of the function of .]]> Wed, 31 Dec 1969 19:00:00 EST Neutral-to-positive cadmium effects on germination and seedling vigor, with and without seed priming. Carvalho MEA, Agathokleous E, Nogueira ML, Brunetto G, Brown PH, Azevedo RA
J Hazard Mater (Apr 2023)

This review gathered and analyzed data about (i) the Cd-induced impacts on seed germination and seedling vigor, and (ii) the use of different priming agents to mitigate Cd-induced impacts on the early plant development. Critical evaluation of the obtained data revealed intriguing results. First, seeds of diverse species can endure exposures to Cd. Such endurance is exhibited as maintenance of or even improvement in the seed germination and vigor (up to 15% and 70%, respectively). Second, the main factors influencing seed tolerance to Cd toxicity are related to temporal variations in anatomical, physiological, and/or biochemical features. Third, Cd can trigger diverse transgenerational effects on plants by shaping seed endophytes, by modulating seed provisioning with resources and regulatory elements, and/or by altering seed (epi)genomics. Fourth, different chemical, biological and physical priming agents can mitigate Cd-induced impacts on seeds, sometimes enhancing their performance over the control (reference) values. Overall, this review shows that the impacts of Cd on seed germination and vigor encompass not only negative outcomes but also neutral and positive ones, depending upon the Cd dose, media properties, plant species and genotypes, plant developmental stage and organ, and management approaches. Increasing our understanding of plant tolerance mechanisms against the growing background Cd pollution is relevant to support breeding programs, agricultural practices, and health-environmental policies.]]> Wed, 31 Dec 1969 19:00:00 EST Mechanisms of transgenerational epigenetic inheritance: lessons from animal model organisms. Santilli F, Boskovic A
Curr Opin Genet Dev (Apr 2023)

Epigenetic inheritance is a phenomenon whereby stochastic or signal-induced changes to parental germline epigenome modulate phenotypic output in one or more subsequent generations, independently of mutations in the genomic DNA. While the number of reported epigenetic inheritance phenomena across phyla is exponentially growing, much remains to be elucidated about their mechanistic underpinnings, and their significance for organismal homeostasis and adaptation. Here, we review the most recent epigenetic inheritance examples in animal models, outlining molecular details behind environmental sensing by the germline, and the functional relationships connecting epigenetic mechanisms and phenotypic traits after fertilization. We touch upon the experimental challenges associated with studying the scope of environmental input on phenotypic outcomes between generations. Finally, we discuss the implications of mechanistic findings from model organisms for the emergent examples of parental effects in human populations.]]> Wed, 31 Dec 1969 19:00:00 EST The impact of histone deacetylase inhibitors on immune cells and implications for cancer therapy. Moran B, Davern M, Reynolds JV, Donlon NE, Lysaght J
Cancer Lett (Apr 2023)

Many cancers possess the ability to suppress the immune response to malignant cells, thus facilitating tumour growth and invasion, and this has fuelled research to reverse these mechanisms and re-activate the immune system with consequent important therapeutic benefit. One such approach is to use histone deacetylase inhibitors (HDACi), a novel class of targeted therapies, which manipulate the immune response to cancer through epigenetic modification. Four HDACi have recently been approved for clinical use in malignancies including multiple myeloma and T-cell lymphoma. Most research in this context has focussed on HDACi and tumour cells, however, little is known about their impact on the cells of the immune system. Additionally, HDACi have been shown to impact the mechanisms by which other anti-cancer therapies exert their effects by, for example, increasing accessibility to exposed DNA through chromatin relaxation, impairing DNA damage repair pathways and increasing immune checkpoint receptor expression. This review details the effects of HDACi on immune cells, highlights the variability in these effects depending on experimental design, and provides an overview of clinical trials investigating the combination of HDACi with chemotherapy, radiotherapy, immunotherapy and multimodal regimens.]]> Wed, 31 Dec 1969 19:00:00 EST Mitochondrial miRNA as epigenomic signatures: Visualizing aging-associated heart diseases through a new lens. Bhatti JS, Khullar N, Vijayvergiya R, Navik U, Bhatti GK, Reddy PH
Ageing Res Rev (Apr 2023)

Aging bears many hard knocks, but heart disorders earn a particular allusion, being the most widespread. Cardiovascular diseases (CVDs) are becoming the biggest concern to mankind due to sundry health conditions directly or indirectly related to heart-linked abnormalities. Scientists know that mitochondria play a critical role in the pathophysiology of cardiac diseases. Both environment and genetics play an essential role in modulating and controlling mitochondrial functions. Even a minor abnormality may prove detrimental to heart function. Advanced age combined with an unhealthy lifestyle can cause most cardiomyocytes to be replaced by fibrotic tissue which upsets the conducting system and leads to arrhythmias. An aging heart encounters far more heart-associated comorbidities than a young heart. Many state-of-the-art technologies and procedures are already being used to prevent and treat heart attacks worldwide. However, it remains a mystery when this heart bomb would explode because it lacks an alarm. This calls for a novel and effective strategy for timely diagnosis and a sure-fire treatment. This review article provides a comprehensive overture of prospective potentials of mitochondrial miRNAs that predict complicated and interconnected pathways concerning heart ailments and signature compilations of relevant miRNAs as biomarkers to plot the role of miRNAs in epigenomics. This article suggests that analysis of DNA methylation patterns in age-associated heart diseases may determine age-impelled biomarkers of heart disease.]]> Wed, 31 Dec 1969 19:00:00 EST Use of histone methyltransferase inhibitors in cancer treatment: A systematic review. Marzochi LL, Cuzziol CI, Nascimento Filho CHVD, Dos Santos JA, Castanhole-Nunes MMU, Pavarino Ã‰C, Guerra ENS, Goloni-Bertollo EM
Eur J Pharmacol (Apr 2023)

Histone modifications are an epigenetic mechanism, and the dysregulation of these proteins is known to be associated with the initiation and progression of cancer. In the search for the development of new and more effective drugs, histone modifications were identified as possible therapeutic targets. Histone methyltransferase (HMT) inhibitors correspond to the third generation of epigenetic drugs capable of writing or deleting epigenetic information. This systematic review summarized the development and prospect for the use of different HMT inhibitors in cancer therapy. An electronic search was applied across CENTRAL, Clinical Trials, Embase, LILACS, LIVIVO, Open Gray, PubMed, Scopus, and Web of Science. Based on the title and abstracts, two authors independently selected eligible studies. After the complete reading of the articles, based on the eligibility criteria, 11 studies were included in the review. Different inhibitors of HMT have been explored in multiple clinical studies, and have shown considerable anti-tumor effects. However, few phase 2 studies have been completed and/or have available results. The most advanced clinical trials mainly include tazemetostat, an Enhancer of zeste homolog 2 (EZH2) inhibitor approved for follicular lymphoma (FL). The use of HMT inhibitors has presented, so far, concise results in the treatment of hematological cancers, moreover, the adverse effects presented after the use of these medicines (alone or in combination) did not show a high level of risk for the patient. These findings, in addition to ongoing clinical studies, can represent a promising future regarding the use of HMT inhibitors in treating different types of cancer.]]> Wed, 31 Dec 1969 19:00:00 EST Advancing CAR T cell therapy through the use of multidimensional omics data. Yang J, Chen Y, Jing Y, Green MR, Han L
Nat Rev Clin Oncol (Apr 2023)

Despite the notable success of chimeric antigen receptor (CAR) T cell therapies in the treatment of certain haematological malignancies, challenges remain in optimizing CAR designs and cell products, improving response rates, extending the durability of remissions, reducing toxicity and broadening the utility of this therapeutic modality to other cancer types. Data from multidimensional omics analyses, including genomics, epigenomics, transcriptomics, T cell receptor-repertoire profiling, proteomics, metabolomics and/or microbiomics, provide unique opportunities to dissect the complex and dynamic multifactorial phenotypes, processes and responses of CAR T cells as well as to discover novel tumour targets and pathways of resistance. In this Review, we summarize the multidimensional cellular and molecular profiling technologies that have been used to advance our mechanistic understanding of CAR T cell therapies. In addition, we discuss current applications and potential strategies leveraging multi-omics data to identify optimal target antigens and other molecular features that could be exploited to enhance the antitumour activity and minimize the toxicity of CAR T cell therapy. Indeed, fully utilizing multi-omics data will provide new insights into the biology of CAR T cell therapy, further accelerate the development of products with improved efficacy and safety profiles, and enable clinicians to better predict and monitor patient responses.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic cues regulating airway development in human lung organoids: Polycomb repressive complex 2 and altered chromatin accessibility determine cell fate. Shirvaliloo M, Akhavan-Sigari R
FASEB J (Apr 2023)

Today, human organoids are becoming an integrated part of genomics and epigenomics, as they provide a platform that can be used for the definite study of molecular and cellular mechanisms occurring at different stages of development, particularly organogenesis, within the human body. Airway development is a complex process heavily influenced by epigenetic regulatory mechanisms in response to environmental changes, and as such, human lung organoids are an indispensable asset for further exploration of these mechanisms as a mode of transition from human in vitro to human ex vivo studies. Cultured primarily in compounds mimicking the extracellular matrix, such as Matrigel, these lung organoids have helped us to come to a better understanding of the role of polycomb repressive complex 2 (PRC2) and enhancer of zeste homolog 2 (EZH2) in lung epithelial cell differentiation and airway development, which was first reported in the FASEB journal in 2019. The following is an extended account of how the histone methylation-regulating PRC2 comes to play in the molding of the human bronchial tree, along with further epigenetic insights based on more recently developed human lung organoids.]]> Wed, 31 Dec 1969 19:00:00 EST Towards a Multi-Omics of Male Infertility. Wagner AO, Turk A, Kunej T
World J Mens Health (Apr 2023)

Infertility is a common problem affecting one in six couples and in 30% of infertile couples, the male factor is a major cause. A large number of genes are involved in spermatogenesis and a significant proportion of male infertility phenotypes are of genetic origin. Studies on infertility have so far primarily focused on chromosomal abnormalities and sequence variants in protein-coding genes and have identified a large number of disease-associated genes. However, it has been shown that a multitude of factors across various omics levels also contribute to infertility phenotypes. The complexity of male infertility has led to the understanding that an integrated, multi-omics analysis may be optimal for unravelling this disease. While there is a vast array of different factors across omics levels associated with infertility, the present review focuses on known factors from the genomics, epigenomics, transcriptomics, proteomics, metabolomics, glycomics, lipidomics, miRNomics, and integrated omics levels. These include: repeat expansions in , , , , and , multiple SNPs, copy number variants in the AZF region, disregulated miRNAs, altered H3K9 methylation, differential , , , and methylation, altered protamine ratios and protein hypo/hyperphosphorylation. This integrative review presents a step towards a multi-omics approach to understanding the complex etiology of male infertility. Currently only a few genetic factors, namely chromosomal abnormalities and Y chromosome microdeletions, are routinely tested in infertile men undergoing intracytoplasmic sperm injection. A multi-omics approach to understanding infertility phenotypes may yield a more holistic view of the disease and contribute to the development of improved screening methods and treatment options. Therefore, beside discovering as of yet unknown genetic causes of infertility, integrating multiple fields of study could yield valuable contributions to the understanding of disease development. Future multi-omics studies will enable to synthesise fragmented information and facilitate biomarker discovery and treatments in male infertility.]]> Wed, 31 Dec 1969 19:00:00 EST Glucocorticoid exposure modifies the miRNA profile of sperm in the guinea pig: Implications for intergenerational transmission. Casciaro C, Hamada H, Kostaki A, Matthews SG
FASEB J (Apr 2023)

Approximately 1%-3% of the adult population are treated with synthetic glucocorticoids (sGCs) for a variety of conditions. Studies have demonstrated that adversities experienced by males prior to conception may lead to abnormal neuroendocrine function and behaviors in offspring and that epigenetic factors including microRNA (miRNA) within sperm may be responsible for driving these effects. However, it remains unclear where in the epididymis sperm miRNA changes are occurring. Here, we hypothesized that sGC exposure will alter the miRNA profile of sperm in the epididymis in a region-specific manner. Adult male guinea pigs were exposed to regular drinking water (Ctrl) or water with the sGC dexamethasone (Dex; 3mg/kg) (n = 6/group) every other day for 48 days. Sperms were collected from epididymal seminal fluid in the caput and cauda regions of the epididymis and total RNA was extracted. miRNAs were assessed by miRNA 4.0 microarray; data were processed by TAC 4.0.1 and R. miRNA analysis revealed one miRNA in the caput that was significantly decreased by Dex in sperm. In the cauda, 31 miRNAs were reduced in sperm following Dex-exposure. The findings of this study demonstrate that Dex-exposure influences miRNA profile of sperm in the cauda but not the caput of the epididymis. This suggests that glucocorticoids target the epididymis to modify sperm miRNA and do not modify the miRNA content during spermiation in the testes.]]> Wed, 31 Dec 1969 19:00:00 EST The kin selection theory of genomic imprinting and modes of reproduction in the eusocial Hymenoptera. da Silva J
Biol Rev Camb Philos Soc (Apr 2023)

Genomic imprinting is known from flowering plants and mammals but has not been confirmed for the Hymenoptera even though the eusocial Hymenoptera are prime candidates for this peculiar form of gene expression. Here, the kin selection theory of genomic imprinting is reviewed and applied to the eusocial Hymenoptera. The evidence for imprinting in eusocial Hymenoptera with the typical mode of reproduction, involving the sexual production of diploid female offspring, which develop into workers or gynes, and the arrhenotokous parthenogenesis of haploid males, is also reviewed briefly. However, the focus of this review is how atypical modes of reproduction, involving thelytokous parthenogenesis, hybridisation and androgenesis, may also select for imprinting. In particular, naturally occurring hybridisation in several genera of ants may provide useful tests of the role of kin selection in the evolution of imprinting. Hybridisation is expected to disrupt the coadaptation of antagonistically imprinted loci, and thus affect the phenotypes of hybrids. Some of the limited data available on hybrid worker reproduction and on colony sex ratios support predictions about patterns of imprinting derived from kin selection theory.]]> Wed, 31 Dec 1969 19:00:00 EST