Further investigation underscores that disruptions in nuclear hormone receptor superfamily signaling can create enduring epigenetic alterations, translating into pathological changes and a heightened susceptibility to various diseases. Early-life exposure, a time of rapid transcriptomic profile evolution, seems to give rise to a more significant impact of these effects. At this time, the regulation and coordination of the complex and interwoven processes of cell proliferation and differentiation defining mammalian development are in progress. Exposure to these elements may also induce alterations in germline epigenetic information, possibly leading to developmental variations and abnormal consequences in later generations. Signaling via thyroid hormone (TH), facilitated by specific nuclear receptors, results in substantial changes to chromatin structure and gene transcription, and simultaneously regulates the factors determining epigenetic modifications. TH's pleiotropic influence in mammals is dynamically regulated during development, responding to the evolving demands of numerous tissues. The molecular mechanisms by which these substances act, along with their precise developmental regulation and significant biological consequences, underscore the crucial role of THs in shaping the epigenetic programming of adult disease and, moreover, through their influence on germ cells, in shaping inter- and transgenerational epigenetic processes. The extant research in these epigenetic areas regarding THs is restricted and in its early phases. Considering their function as epigenetic modifiers and their tightly controlled developmental actions, we review here some findings that emphasize how altered thyroid hormone activity might influence the developmental programming of adult traits and the phenotypic expression of subsequent generations, mediated by germline transmission of modified epigenetic information. Recognizing the relatively high incidence of thyroid conditions and the capacity of certain environmental agents to disrupt thyroid hormone (TH) activity, the epigenetic effects of abnormal thyroid hormone levels may be important factors in the non-genetic pathogenesis of human disease.
Endometriosis is a medical condition defined by the presence of endometrial tissue in places other than within the uterine cavity. This debilitating condition, progressive in nature, impacts up to 15% of women within their reproductive years. Because endometriosis cells can express estrogen receptors (ER, Er, GPER) and progesterone receptors (PR-A, PR-B), the patterns of their growth, cyclical proliferation, and tissue breakdown are similar to those seen in the endometrium. The specific reasons for the development and spread of endometriosis remain a subject of ongoing research. The most widely accepted implantation theory centers on the retrograde transport of viable menstrual endometrial cells, which retain the capacity for attachment, proliferation, differentiation, and invasion into the surrounding pelvic tissue. The abundant cell population found in the endometrium, endometrial stromal cells (EnSCs), exhibit clonogenic potential and share similarities with mesenchymal stem cells (MSCs). Hence, the malfunctioning of endometrial stem cells (EnSCs) is potentially responsible for the formation of endometrial implants in endometriosis. Recent studies reveal the underestimated participation of epigenetic processes in the pathology of endometriosis. The role of hormone-induced epigenetic modifications in the genome, specifically affecting endometrial stem cells (EnSCs) and mesenchymal stem cells (MSCs), was considered crucial in understanding the etiology of endometriosis. In the development of a breakdown in epigenetic homeostasis, excess estrogen exposure and progesterone resistance were additionally recognized as critical components. The purpose of this review was to collate current data on the epigenetic factors influencing EnSCs and MSCs, and the subsequent changes in their properties brought about by imbalances in estrogen and progesterone levels, relating these to endometriosis's origin and progression.
10% of women in their reproductive years experience endometriosis, a benign gynecological condition marked by the presence of endometrial glands and stroma outside the uterine cavity. Endometriosis's impact on health ranges from pelvic discomfort to catamenial pneumothorax, but it is mainly recognized for its association with severe chronic pelvic pain, painful menstrual periods, deep pain during sexual intercourse, and problems related to reproduction. Endometriosis's intricate development involves endocrine system malfunction, specifically estrogen's dominance and progesterone's resistance, coupled with inflammatory responses, and ultimately the problems with cell proliferation and the growth of nerves and blood vessels. The current chapter examines the principal epigenetic processes impacting estrogen receptors (ERs) and progesterone receptors (PRs) within the context of endometriosis. Endometriosis's complex regulatory network involves multiple epigenetic processes acting upon the expression of receptor genes. These include, but are not limited to, the modulation of transcription factors, DNA methylation, histone modifications, microRNAs, and long noncoding RNAs. This uncharted area of investigation may lead to crucial clinical implications, including the creation of epigenetic medications for endometriosis and the discovery of specific and early disease biomarkers.
Type 2 diabetes (T2D) is a metabolic disorder, marked by -cell dysfunction and insulin resistance in the liver, muscles, and adipose tissue. While the detailed molecular mechanisms leading to its formation remain unclear, investigations into its causes repeatedly reveal a multifactorial involvement in its development and progression in most situations. It has been observed that regulatory interactions, mediated by epigenetic modifications including DNA methylation, histone tail modifications, and regulatory RNAs, contribute substantially to T2D. Regarding T2D's pathological features, this chapter discusses the dynamic impact of DNA methylation.
Mitochondrial dysfunction plays a critical role in the genesis and progression of numerous chronic conditions, as highlighted in a large number of research studies. Mitochondria, the powerhouses of cellular energy production, hold a distinct genetic blueprint, unlike other cytoplasmic organelles. Through investigation of mitochondrial DNA copy number, most research efforts to date have been directed towards substantial structural modifications of the complete mitochondrial genome and their impact on human diseases. By utilizing these techniques, researchers have discovered a correlation between mitochondrial dysfunction and the development of cancers, cardiovascular diseases, and metabolic problems. Like the nuclear genome, the mitochondrial genome may be subject to epigenetic modifications, including DNA methylation, which potentially elucidates the relationship between diverse environmental factors and health. Recently, a shift in perspective has occurred regarding human health and disease by considering the concept of the exposome, which aims to meticulously describe and measure each exposure a person encounters during their lifetime. Environmental contaminants, occupational exposures, heavy metals, alongside lifestyle and behavioral elements, make up this group. Tezacaftor manufacturer This chapter's focus is on the current research connecting mitochondria to human health, including a review of mitochondrial epigenetics and a detailed account of experimental and epidemiological studies designed to investigate the relationships between specific environmental factors and mitochondrial epigenetic changes. To propel the field of mitochondrial epigenetics, this chapter's conclusion highlights the necessity of future epidemiologic and experimental research directions.
During the metamorphic transition in amphibian intestines, apoptosis affects the great majority of larval epithelial cells, leaving a minority to dedifferentiate into stem cells. Adult epithelial tissue is consistently recreated by stem cells that actively multiply and then produce new cells, similar to the mammalian model of continuous renewal throughout adulthood. Experimental induction of larval-to-adult intestinal remodeling is achievable via thyroid hormone (TH) interactions with the developing stem cell niche's surrounding connective tissue. Subsequently, the amphibian intestine offers a prime example of how stem cells and their surrounding environment are established during embryonic growth. Tezacaftor manufacturer The identification and extensive analysis of TH response genes in the Xenopus laevis intestine, over the past three decades, have shed light on the TH-induced and evolutionarily conserved mechanism of SC development at the molecular level. This analysis has used wild-type and transgenic Xenopus tadpoles to examine expression and function. Remarkably, the mounting data reveals that thyroid hormone receptor (TR) epigenetically influences the expression of genes that respond to thyroid hormone, playing a role in the remodeling process. Within the context of SC development, this review underscores recent progress in understanding the epigenetic regulation of gene expression mediated by TH/TR signaling in the X. laevis intestine. Tezacaftor manufacturer This study proposes that two TR subtypes, TR and TR, perform distinct tasks in the intestinal stem cell developmental process, achieved via differing histone modifications in various cellular compartments.
PET imaging with the radiolabeled form of estradiol, 16-18F-fluoro-17-fluoroestradiol (18F-FES), provides a noninvasive, whole-body assessment of estrogen receptor (ER). The U.S. Food and Drug Administration has granted approval to 18F-FES as a diagnostic agent for the detection of ER-positive lesions in patients with recurrent or metastatic breast cancer, acting as a useful adjunct to biopsy procedures. The Society of Nuclear Medicine and Molecular Imaging (SNMMI) formed a panel of experts to scrutinize the body of published research concerning 18F-FES PET in patients with ER-positive breast cancer, and to define appropriate use criteria (AUC). Published in 2022 and available at https//www.snmmi.org/auc is the comprehensive report of the SNMMI 18F-FES work group, encompassing their findings, discussions, and example clinical scenarios.