Impact of endocrine-active compounds on adrenal androgen production in pigs during neonatal period.

This study investigated the impact of neonatal exposure to endocrine-active compounds (EACs): flutamide (antiandrogen), 4-tert-octylphenol (an estrogenic compound), and methoxychlor (an organochlorine insecticide exhibiting estrogenic, antiestrogenic and antiandrogenic activities) on androgen production within porcine adrenal glands. The expression of genes related to androgen synthesis and the level of androgen production were analyzed (i) in the adrenal glands of piglets exposed to EACs during the first 10 days of life (in vivo study), and (ii) in adrenal explants from sow-fed or formula-fed 10-day-old piglets incubated with EACs (ex vivo study). EACs affected the expression of genes linked to adrenal androgen biosynthesis. The prominent effect of methoxychlor on downregulation of StAR, CYP11A1 and HSD3B and upregulation of CYP17A1 and SULT2A1 were demonstrated. Furthermore, our study revealed divergent response to EACs between sow-fed and formula-fed piglets, suggesting that natural feeding may provide protection against adverse EACs effects, particularly those interfering with estrogens action.

The Role of Endocrine Disruption Chemical-Regulated Aryl Hydrocarbon Receptor Activity in the Pathogenesis of Pancreatic Diseases and Cancer.

The aryl hydrocarbon receptor (AHR) serves as a ligand-activated transcription factor crucial for regulating fundamental cellular and molecular processes, such as xenobiotic metabolism, immune responses, and cancer development. Notably, a spectrum of endocrine-disrupting chemicals (EDCs) act as agonists or antagonists of AHR, leading to the dysregulation of pivotal cellular and molecular processes and endocrine system disruption. Accumulating evidence suggests a correlation between EDC exposure and the onset of diverse pancreatic diseases, including diabetes, pancreatitis, and pancreatic cancer. Despite this association, the mechanistic role of AHR as a linchpin molecule in EDC exposure-related pathogenesis of pancreatic diseases and cancer remains unexplored. This review comprehensively examines the involvement of AHR in EDC exposure-mediated regulation of pancreatic pathogenesis, emphasizing AHR as a potential therapeutic target for the pathogenesis of pancreatic diseases and cancer.

Combined effects of binary mixtures of 17ß-estradiol and testosterone in western mosquitofish (Gambusia affinis) after full life-cycle exposure.

Estrogens and androgens are typical steroid hormones and often occur together in contaminated aquatic environments, but their mixed effects in aquatic organisms have been less well reported. In this study, the endocrine disrupting effects of binary mixtures of 17ß-estradiol (E2) and testosterone (T) in western mosquitofish (Gambusia affinis) were assessed by analyzing the sex ratio, secondary sex characteristics, gonadal histology, and transcriptional expression of target genes related to the hypothalamic-pituitary-gonadal (HPG) axis in G. affinis (from embryos) continuously exposed to E2 (50 ng/L), T (T1: 50 ng/L; T2: 200 ng/L), and mixtures of both (E2 + T1: 50 + 50 ng/L; E2 + T2: 50 + 200 ng/L) for 119 d. The results showed that exposure to E2 + T1 and E2 + T2 reduced the length ratio of ray 4/6 ratio in male G. affinis, suggesting feminized phenomenon in male G. affinis. Furthermore, 16.7-38.5 % of female G. affinis showed masculinized anal fins and hemal spines when exposed to T alone and in combination with E2. Importantly, the transcriptional levels of certain target genes related to the HPG axis were significantly altered in G. affinis following exposure to E2 and T alone and in combinations. Moreover, exposure to E2 and T in combinations can lead to combined effects (such as synergistic and antagonistic effects) on the transcriptional levels of some genes. These results collectively suggest that exposure to environmentally relevant concentrations of E2 and T alone and in mixtures can impact the endocrine system of G. affinis, and may pose potential risks in aquatic systems.

Endocrine disrupting potential of total and bioaccessible extracts of dust from seven different types of indoor environment.

Information on the indoor environment as a source of exposure with potential adverse health effects is mostly limited to a few pollutant groups and indoor types. This study provides a comprehensive toxicological profile of chemical mixtures associated with dust from various types of indoor environments, namely cars, houses, prefabricated apartments, kindergartens, offices, public spaces, and schools. Organic extracts of two different polarities and bioaccessible extracts mimicking the gastrointestinal conditions were prepared from two different particle size fractions of dust. These extracts were tested on a battery of human cell-based bioassays to assess endocrine disrupting potentials. Furthermore, 155 chemicals from different pollutant groups were measured and their relevance for the bioactivity was determined using concentration addition modelling. The exhaustive and bioaccessible extracts of dust from the different microenvironments interfered with aryl hydrocarbon receptor, estrogen, androgen, glucocorticoid, and thyroid hormone (TH) receptor signalling, and with TH transport. Noteably, bioaccessible extracts from offices and public spaces showed higher estrogenic effects than the organic solvent extracts. 114 of the 155 targeted chemicals were detectable, but the observed bioactivity could be only marginally explained by the detected chemicals. Diverse toxicity patterns across different microenvironments that people inhabit throughout their lifetime indicate potential health and developmental risks, especially for children. Limited data on the endocrine disrupting potency of relevant chemical classes, especially those deployed as replacements for legacy contaminants, requires further study.

Cuidado ás pessoas com agravos endocrinos e metabólicos / Care for people with endocrine and metabolic problems

O objetivo desse trabalho é descrever a sistematização da Assistência de Enfermagem a pessoas com agravos endócrinos e metabólicos pautado na teoria de Calista Roy. Metodologia: Trata-se de um relato de experiência através da aplicação da Sistematização da Assistência de Enfermagem (SAE), voltado para pessoas com agravos endócrinos e metabólicos no contexto hospitalar. Resultados e discussão: Foi aplicado a teoria da adaptação nas seis fases da Teoria de Calista Roy e foi elaborado diagnósticos de enfermagem para os quatro modos de adaptação: fisiológico, interdependência, autoconceito e função de papel. Considerações finais: Ao aplicar a SAE no indivíduo com agravos endócrinos e metabólicos a enfermeira deve realizá-lo em todas as suas etapas, e utilizar os protocolos para oferecer um cuidado holístico e integral, visando a promoção da saúde, prevenção de risco potencial e adaptação diante das necessidades em saúde.(AU)

The aim of this study is to describe the systematization of nursing care for people with endocrine and metabolic disorders, based on Calista Roy's theory. Methodology: This is an experience report on the application of the Systematization of Nursing Care (SNC) to people with endocrine and metabolic disorders in a hospital setting. Results and discussion: The theory of adaptation was applied in the six phases of Calista Roy's theory and nursing diagnoses were drawn up for the four modes of adaptation: physiological, interdependence, self-concept and role function. Final considerations: When applying the SNC to individuals with endocrine and metabolic disorders, the nurse must carry it out in all its stages, and use the protocols to offer holistic and comprehensive care, aimed at promoting health, preventing potential risks and adapting to health needs.(AU)

El objetivo de este estudio es describir la sistematización de los cuidados de enfermería a personas con trastornos endocrinos y metabólicos, basándose en la teoría de Calista Roy. Metodología: Se trata de un informe de experiencia sobre la aplicación de la Sistematización de los Cuidados de Enfermería (SNC) a personas con trastornos endocrinos y metabólicos en un entorno hospitalario. Resultados y discusión: Se aplicó la teoría de la adaptación en las seis fases de la teoría de Calista Roy y se elaboraron diagnósticos de enfermería para los cuatro modos de adaptación: fisiológica, interdependencia, autoconcepto y función de rol. Consideraciones finales: Al aplicar el SNC a individuos con trastornos endocrinos y metabólicos, la enfermera debe llevarlo a cabo en todas sus fases, y utilizar los protocolos para ofrecer cuidados holísticos e integrales, dirigidos a promover la salud, prevenir riesgos potenciales y adaptarse a las necesidades de salud.(AU)

Evaluation of fish pituitary spheroids to study annual endocrine reproductive control.

The pituitary gland is a small endocrine gland located below the hypothalamus. This gland releases several important hormones and controls the function of many other endocrine system glands to release hormones. Fish pituitary hormonal cells are controlled by neuroendocrine and sex steroid feedback. To study the complex pituitary function in vivo, we established an in vitro pituitary spheroid assay and evaluated its suitability for monitoring the annual reproductive physiological conditions in Takifugu rubripes, also known as torafugu, is one of the most economically important species distributed in the northwestern part of the Pacific Ocean, in the western part of the East China Sea, and in more northern areas near Hokkaido, Japan. Fish pituitary spheroids can be easily constructed in liquid or solid plates. The culture medium (L-15) made the aggregation faster than MEM (Hank's). A Rho-kinase inhibitor (Y-27632, 10 µM) and/or fish serum (2.5 %) also promoted spheroid formation. Laser confocal microscopy analysis of spheroids cultured with annual serum of both sexes revealed that luteinizing hormone (LH) synthesis has the highest peak in the final maturation stage (3 years old, May) in accordance with the highest serum sex steroid levels; in contrast, follicle stimulating hormone (FSH) synthesis has no correlation with the dose of serum or nutrients. Similarly, 3D cell propagation assays using female serum showed that total pituitary cells displayed the highest proliferation at puberty onset (2 years old, October) before half a year of the spawning season. These results indicate that pituitary spheroids are useful in vitro models for monitoring the reproductive physiological status of fish in vivo and may be applicable to the in vitro screening of environmental chemicals and bioactive compounds affecting reproductive efficiency in aquaculture.

Multi-omics Investigations in Endocrine Systems and Their Clinical Implications.

Innovative techniques such as the "omics" can be a powerful tool for the understanding of intracellular pathways involved in homeostasis maintenance and identification of new potential therapeutic targets against endocrine-metabolic disorders. Over the last decades, proteomics has been extensively applied in the study of a wide variety of human diseases, including those involving the endocrine system. Among the most endocrine-related disorders investigated by proteomics in humans are diabetes mellitus and thyroid, pituitary, and reproductive system disorders. In diabetes, proteins implicated in insulin signaling, glucose metabolism, and ß-cell activity have been investigated. In thyroid diseases, protein expression alterations were described in thyroid malignancies and autoimmune thyroid illnesses. Additionally, proteomics has been used to investigate the variations in protein expression in adrenal cancers and conditions, including Cushing's syndrome and Addison's disease. Pituitary tumors and disorders including acromegaly and hypopituitarism have been studied using proteomics to examine changes in protein expression. Reproductive problems such as polycystic ovarian syndrome and endometriosis are two examples of conditions where alterations in protein expression have been studied using proteomics. Proteomics has, in general, shed light on the molecular underpinnings of many endocrine-related illnesses and revealed promising biomarkers for both their detection and treatment. The capacity of proteomics to thoroughly and objectively examine complex protein mixtures is one of its main benefits. Mass spectrometry (MS) is a widely used method that identifies and measures proteins based on their mass-to-charge ratio and their fragmentation pattern. MS can perform the separation of proteins according to their physicochemical characteristics, such as hydrophobicity, charge, and size, in combination with liquid chromatography. Other proteomics techniques include protein arrays, which enable the simultaneous identification of several proteins in a single assay, and two-dimensional gel electrophoresis (2D-DIGE), which divides proteins depending on their isoelectric point and molecular weight. This chapter aims to summarize the most relevant proteomics data from targeted tissues, as well as the daily rhythmic variation of relevant biomarkers in both physiological and pathophysiological conditions within the involved endocrine system, especially because the actual modern lifestyle constantly imposes a chronic unentrained condition, which virtually affects all the circadian clock systems within human's body, being also correlated with innumerous endocrine-metabolic diseases.

The role of microbial metabolites in endocrine tumorigenesis: From the mechanistic insights to potential therapeutic biomarkers.

Microbial metabolites have been indicated to communicate with the host's endocrine system, regulating hormone production, immune-endocrine communications, and interactions along the gut-brain axis, eventually affecting the occurrence of endocrine cancer. Furthermore, microbiota metabolites such as short-chain fatty acids (SCFAs) have been found to affect the tumor microenvironment and boost immunity against tumors. SCFAs, including butyrate and acetate, have been demonstrated to exert anti-proliferative and anti-protective activity on pancreatic cancer cells. The employing of microbial metabolic products in conjunction with radiation and chemotherapy has shown promising outcomes in terms of reducing treatment side effects and boosting effectiveness. Certain metabolites, such as valerate and butyrate, have been made known to improve the efficiency of CAR T-cell treatment, whilst others, such as indole-derived tryptophan metabolites, have been shown to inhibit tumor immunity. This review explores the intricate interplay between microbial metabolites and endocrine tumorigenesis, spanning mechanistic insights to the discovery of potential therapeutic biomarkers.

The effect of gonadotropin-releasing hormone analog treatment on the endocrine system in central precocious puberty patients: a meta-analysis.

OBJECTIVES: Gonadotropin-releasing hormone (GnRHa) is the first choice for the treatment of patients with central precocious puberty (CPP). However, the effects of GnRHa on the endocrine system of CPP patients, including insulin sensitivity, lipid level, thyroid function, bone mineral density (BMD), and testosterone (T) level, are currently contradictory. Therefore, the long-term safety of GnRHa therapy remains controversial. CONTENT: A systematic literature search was performed using PubMed, Embase, Cochrane Library, and CNKI databases. The changes in HOMA-IR, TG, LDL-C, HDL-C, TSH, FT3, FT4, T, and BMD in CPP patients before and after GnRHa treatment were compared by meta-analysis. As the heterogeneity between studies, we estimated standard deviation mean differences (SMDs) and 95 % confidence intervals (CIs) using a random-effects model. Egger's test was used to assess publication bias. SUMMARY: A total of 22 studies were included in our meta-analysis. Compared with before GnRHa treatment, there were no statistically significant differences in endocrine indicators including HOMA-IR, TG, LDL-C, HDL-C, TSH, FT4, FT3, T, and BMD of CPP patients treated with GnRHa. OUTLOOK: Treatment with GnRHa for central precocious puberty will not increase the adverse effect on the endocrine system.

Methyltransferase-like 3 modifications of RNAs: Implications for the pathology in the endocrine system.

Methyltransferase-like 3 (METTL3) is the most well-known element of N6-methyladenosine modification on RNAs. METTL3 deposits a methyl group onto target RNAs to modify their expression, ultimately regulating various physiological and pathological events. Numerous studies have suggested the significant role of METTL3 in endocrine dysfunction and related disorders. However, reviews that summarize and interpret these studies are lacking. In this review, we systematically analyze such studies, including obesity, type 2 diabetes mellitus (T2DM), T2DM-induced diseases, pancreatic cancer, and thyroid carcinoma. This review indicates that METTL3 contributes remarkably to the endocrine dysfunction and progression of obesity, T2DM, T2DM-induced diseases, pancreatic cancer, and thyroid carcinoma. In conclusion, this review provides a comprehensive interpretation of the mechanism via which METTL3 functions on RNAs and regulates various endocrine dysfunction events and suggest potential associated correlations. Our review, thus, provides a valuable reference for further fundamental studies and clinical applications.

Grouping of esters of 4-hydroxybenzoic acid for hazard assessment.

Hazardous properties of a large number of esters of 4-hydroxybenzoic acid (parabens) have been proposed by ECHA to be assessed as a group. We recommend to restrict the grouping approach to short chain esters, i.e. methyl, ethyl, propyl and butyl paraben which are very similar in chemical structures, physicochemical properties, toxicokinetics, and hazardous properties. While these parabens show a weak estrogenicity in some in vitro or in vivo screening assays, they do not induce estrogen-receptor-mediated adverse effects in intact animals. Therefore, there is no support regarding classification and labeling of endocrine disruption or reproductive toxicity of these parabens.

Human gut microbiota and endocrinology: paradigm shift from genome to its regulation.

Over the last two decades, it has become clear that the human gut microbiota, a complex community of bacteria, archaea, fungi and viruses, are a critical determinant of human health and disease. Microbiota-derived metabolites provide the host with energy, protect against pathogens, modulate immune and endocrine systems as well as the level of reactive oxygen species in the gut. It has come with no surprise that the human gut microbiota is also linked to the production, utilisation and regulation of host hormones. This implies that the gut microbiota is capable of influencing human behaviour, appetite regulation and metabolism as well as development and immunity. Many of the advances in the field of crosstalk between the gut microbiota and host health, disease and behaviours are generally based on DNA analyses of microbial populations and transplantation of monocultured commensal species to germ-free animals. Recent reports on the activity of the gut microbiota in gastrointestinal diseases such as inflammatory bowel disease and colorectal cancer have highlighted two important points. First, microbial DNA-based abundance does not always correlate with their level of activity and secondly, that metabolism of the complex gut microbiota is regulated by host health status, including the production and metabolism of several human hormones. In this review, we will discuss the lessons learnt from studying the activity and metabolism of the human gut microbiota in health and across gastrointestinal diseases, and how these findings can shape future research on the microbiome-gut-endocrine axis.

Isothiazolinone dysregulates the pattern of miRNA secretion: Endocrine implications for neurogenesis.

Isothiazolinones are extensively used as preservatives and disinfectants in personal care products and household items. The unintended exposure of humans and animals to isothiazolinones has led to increasing concerns about their health hazards. The compound 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT), a representative isothiazolinone, can simultaneously induce endocrine disruption and neurotoxicity. However, the underlying mechanisms and linkages remain unclear. Our purpose was to elucidate the role of miRNAs as the signaling communicator during the crosstalk between endocrine and nervous systems in response to DCOIT stress. H295R cells were exposed to DCOIT, after which the alterations in intracellular miRNA composition, exosome secretory machinery, and extracellular miRNA composition were examined. Then, a PC12 cell line of neuronal differentiation potential was cultured with the extract of extracellular miRNAs from DCOIT-exposed H295R cell media to explore the functional implications in neurogenesis. The results showed that DCOIT exposure resulted in 349 differentially expressed miRNAs (DEMs) in H295R cells, which were closely related to the regulation of multiple endocrine pathways. In the media of H295R cells exposed to DCOIT, 66 DEMs were identified, showing distinct compositions compared to intracellular DEMs with only 2 common DEMs (e.g., novel-m0541-5p of inverse changes in the cell and medium). Functional annotation showed that extracellular DEMs were not only associated with sex endocrine synchronization, but were also implicated in nervous system development, morphogenesis, and tumor. Incubating PC12 cells with the extracellular exosomes (containing miRNAs) from DCOIT-exposed H295R cells significantly increased the neurite growth, promoted neuronal differentiation, and shaped the transcriptomic fingerprint, implying that miRNAs may communicate transduction of toxic information of DCOIT in endocrine system to neurons. Overall, the present findings provide novel insight into the endocrine disrupting and neural toxicity of DCOIT. The miRNAs have the potential to serve as the epigenetic mechanism of systems toxicology.

Adipose tissue as a cause of endocrine dysfunction.

Adipose tissue is a large hormonally active organ that secretes several substances (adipokines), and an important site for the synthesis and metabolism of steroid hormones. With energy balance, the secretory and metabolic activity of adipose tissue determines the normal function of many organs, including the endocrine glands. However, in the course of overweight and obesity, adverse changes occur in the structure and function of adipocytes. Obesity-related adipose tissue dysfunction translates into a change in the profile of secreted adipokines, and it impairs steroidogenesis. These phenomena contribute to the development of obesity-related complications, which also affect the major tropic axes regulating the endocrine glands. However, there is increasing evidence that weight reduction is an effective treatment for obesity-related adipose tissue dysfunction, thereby restoring endocrine function. This narrative review presents the impact of adipose tissue on endocrine gland activity both in the physiological state and in obesity-related dysfunction. It also discusses how functional (related to excess adiposity) changes in the endocrine system can be restored with effective treatment of obesity.

Long-term effects of COVID-19 on the endocrine system - a pilot case-control study.

Background: Coronavirus disease 2019 (COVID-19) has permanently changed the world. Despite having been a pandemic for nearly 3 years, the mid- and long-term complications of this disease, including endocrine disorders, remain unclear. Our study aimed to evaluate the lasting effects of COVID-19 on the endocrine system 6 months after initial infection. Methods: We compared patients who underwent COVID-19 to age- and sex-matched subjects from a population-based study conducted before the pandemic. We evaluated differences in multiple parameters related to metabolism and the endocrine system including fasting glucose, insulin, lipids, body composition, thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), anti-thyroglobulin (aTG) and anti-thyroid peroxidase (aTPO) antibodies, prolactin, cortisol, testosterone, and estradiol. Results: We found significantly lower levels of fT3 and fT4, accompanied by higher levels of TSH and aTPO antibodies, in COVID-19 survivors. Moreover, we found that patients who underwent SARS-CoV2 infection had higher levels of prolactin and lower levels of testosterone than controls. Interestingly, differences in testosterone levels were observed only in male subjects. We did not detect significant differences in body composition or metabolic and glycemic parameters between cases and controls, except for significantly higher values of the HOMA2-B index in COVID-19 survivors. Conclusion: Our study indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection might have long-term consequences on the endocrine system, including the suppressed function of the thyroid gland, prolactin, and male sex hormone secretion. Moreover, we showed that in a 6-month follow-up, COVID-19 had no consequences on glycemic parameters, lipid profiles, liver function, body composition, cortisol levels, and estradiol levels.

A battery of in silico models application for pesticides exerting reproductive health effects: Assessment of performance and prioritization of mechanistic studies.

Given the high attention to endocrine disrupting chemicals (EDC), there is an urgent need for the development of rapid and reliable approaches for the screening of large numbers of chemicals with respect to their endocrine disruption potential. This study aimed at the assessment of the correlation between the predicted results of a battery of in silico tools and the reported observed adverse effects from in vivo reproductive toxicity studies. We used VirtualToxLab (VTL) software and the EndocrineDisruptome (ED) online tool to evaluate the binding affinities to nuclear receptors of 17 pesticides, 7 of which were classified as reprotoxic substances under Regulation (EC) No 1272/2008 on the classification, labelling and packaging of substances and mixtures (CLP). Then, we aligned the results of the in silico modelling with data from ToxCast assays and in vivo reproductive toxicity studies. We combined results from different in silico tools in two different ways to improve the characteristics of their predictive performance. Reproductive toxicity can be caused by various mechanisms; however, in this study, we demonstrated that the use of a battery of in silico tools for assessing the binding to nuclear receptors can be useful for identifying hazardous compounds and for prioritizing further studies.

An international cross-laboratory survey on fish vitellogenin analysis: Methodological challenges and opportunities for best practice.

Vitellogenin (VTG) is a biomarker for possible endocrine activity of chemicals acting via the estrogen, androgen, or steroidogenesis pathways. VTG is assessed in standardised fish guideline studies conducted for regulatory safety assessment of chemicals. VTG data can be highly variable leading to concerns for potential equivocal, false positive and/or negative outcomes. Consequently, additional fish testing may be required to address uncertainties in the VTG response, and possibly erroneous/missed identification of endocrine activity. To better understand the technical challenges of VTG assessment and reporting for regulatory purposes, a survey was sent to 27 testing laboratories performing these analyses. The survey results from 16 respondents (6 from the UK, 3 from the USA, and 7 from the EU) were analysed and discussed in a follow-up webinar. High variability in background VTG concentrations was widely acknowledged and thought to be associated with fish batch, husbandry, laboratory practices, and several methodological aspects. These include sample collection and storage, VTG quantification, data handling, and the benchmarks used for data acceptability. Information gathered in the survey provides a basis for improving and harmonizing the measurement of VTG in fish, and an opportunity to reassess the suitability of current acceptability criteria in test guidelines.

Modulation of fetoplacental growth, development and reproductive function by endocrine disrupters.

Maternal endocrine homeostasis is vital to a successful pregnancy, regulated by several hormones such as human chorionic gonadotropin, estrogen, leptin, glucocorticoid, insulin, prostaglandin, and others. Endocrine stress during pregnancy can modulate nutrient availability from mother to fetus, alter fetoplacental growth and reproductive functions. Endocrine disrupters such as bisphenols (BPs) and phthalates are exposed in our daily life's highest volume. Therefore, they are extensively scrutinized for their effects on metabolism, steroidogenesis, insulin signaling, and inflammation involving obesity, diabetes, and the reproductive system. BPs have their structural similarity to 17-ß estradiol and their ability to bind as an agonist or antagonist to estrogen receptors to elicit an adverse response to the function of the endocrine and reproductive system. While adults can negate the adverse effects of these endocrine-disrupting chemicals (EDCs), fetuses do not equip themselves with enzymatic machinery to catabolize their conjugates. Therefore, EDC exposure makes the fetoplacental developmental window vulnerable to programming in utero. On the one hand prenatal BPs and phthalates exposure can impair the structure and function of the ovary and uterus, resulting in placental vascular defects, inappropriate placental expression of angiogenic growth factors due to altered hypothalamic response, expression of nutrient transporters, and epigenetic changes associated with maternal endocrine stress. On the other, their exposure during pregnancy can affect the offspring's metabolic, endocrine and reproductive functions by altering fetoplacental programming. This review highlights the latest development in maternal metabolic and endocrine modulations from exposure to estrogenic mimic chemicals on subcellular and transgenerational changes in placental development and its effects on fetal growth, size, and metabolic & reproductive functions.

Acupuncture as multi-targeted therapy for the multifactorial disease obesity: a complex neuro-endocrine-immune interplay.

The prevalence of obesity has reached pandemic dimensions. It is associated with multiple comorbidities and is becoming a clinical and public health threat. Obesity is a multifactorial disease with a complex pathophysiology and interplay of various systems. A strong interplay exists between the neuro-endocrine system, the immune system with systemic chronic low-grade inflammation, and microbiome dysbiosis that can lead to the development of obesity, which in turn can exacerbate each of these factors, hence creating a vicious cycle. The conventional treatment with lifestyle modifications such as diet, physical exercise, pharmacotherapy, and bariatric surgery does not always result in sufficient weight control thus paving the way for other strategies. As one such strategy, acupuncture is increasingly used worldwide to treat obesity. This narrative review outlines the evidence for this neuro-endocrine-immune interplay in the pathophysiology of obesity. Furthermore, the existing experimental and clinical evidence of acupuncture as a multi-targeted therapy for obesity is explained and future research perspectives are discussed.