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Women exposed to diethylstilbestrol (DES) in utero were at elevated risk of clear-cell adenocarcinoma of the vagina and cervix (CCA) as young women. Previous research suggested that this elevated risk of CCA may persist into adulthood. We extended a published analysis to measure CCA risk as these women aged.Standardized incidence ratios (SIR) compared CCA risk among women born from 1947 through 1971 (the DES-era) to CCA risk among the comparison group of women born prior to 1947, using registry data that covered the US population.Incidence rates of CCA among both cohorts increased with age. Among the DES-era birth cohort, higher rates of CCA were observed across all age groups except 55-59 years. SIR estimates had wide confidence intervals that often included the null value.Results are consistent with prior research and suggest an elevated risk of CCA in midlife and at older ages among women exposed in utero to DES. These results highlight unresolved issues regarding cancer risk among aging DES daughters and appropriate screening guidance. The examination of population-based cancer surveillance data may be a useful tool for monitoring trends in the incidence of other rare cancers over time among specific birth cohorts.

In the current study, the C18-modified halloysite was fabricated via silylation reaction and subsequently used as sorbent in matrix solid-phase dispersion (MSPD) for the extraction of bisphenol A and diethylstilbestrol from human placenta, followed by high-performance liquid chromatography-tandem mass spectrometry analysis. The as-prepared sorbent was characterized by scanning electron microscopy, energy-dispersive spectrometry, Fourier transform infrared spectroscopy, X-ray diffraction, and thermo-gravimetric analysis. Varied parameters such as methanol concentration in wash solvent, pH and salt concentration in elution solvent, elution volume, and mass ratio of sample to sorbent were optimized. The adsorption capacities of bisphenol A and diethylstilbestrol on the developed C18-modified halloysite were 6.3 and 14.2 mg g

This review summarizes key findings from the US National Cancer Institute (NCI) diethylstilbestrol (DES) Combined Cohort Study with a focus on the results of the NCI Third Generation Study, a cohort of DES-exposed and -unexposed granddaughters. Findings to date from the Third Generation Study are discussed in the context of other research efforts and case reports, suggesting an intergenerational heritability of DES-related effects. The DES story serves as a model for the influence of endocrine disrupting chemicals on human health. It also serves as a warning of the special hazards of pregnancy exposures, and more broadly, of the potential for invisible health consequences arising from new or changing exposures. Summary sentence Diethylstilbestrol is associated with adverse health outcomes in women exposed during pregnancy and in prenatally exposed offspring, particularly daughters; evidence suggests that exposure health effects may extend to the next generation.

Background: The influence of prenatal diethylstilbestrol (DES) exposure on cancer incidence among middle-aged men has not been well-characterized. We investigated whether exposure to DES before birth impacts overall cancer risk, and risk of site-specific cancers. Methods: Men (mean age in 2016 = 62.0 years) who were or were not prenatally DES exposed were identified between 1953 and 1994 and followed for cancer primarily via questionnaire approximately every 5 years between 1994 and 2016. The overall and site-specific cancer rates of the two groups were compared using Poisson regression and proportional hazards modeling with adjustment for age. Results: DES exposure was not associated with either overall cancer [hazard ratio (HR), 0.94; 95% confidence interval (CI), 0.77–1.15] or total prostate cancer rates (HR, 0.95; 95% CI, 0.68–1.33), but was inversely associated with urinary tract cancer incidence (HR, 0.48; 95% CI, 0.23–1.00). Conclusions: There was no increase in either overall or prostate cancer rates among men prenatally DES exposed relative to those unexposed. An unexpected risk reduction was observed for urinary system cancers among the exposed relative to those unexposed. These findings suggest that prenatal DES exposure is unlikely to be an important contributor to cancer development in middle-aged men. Impact: The results of this study could lend reassurance to middle-aged men who were prenatally DES exposed that their exposure does not adversely influence their overall cancer risk.

In the early 1960's, at Professor Bern's laboratory, University of California, Berkeley) in the US, Takasugi discovered ovary-independent, persistent vaginal changes in mice exposed neonatally to estrogen, which resulted in vaginal cancer later in life. Reproductive abnormalities in rodents were reported as a result of perinatal exposure to various estrogenic chemicals. Ten years later, vaginal cancers were reported in young women exposed in utero to the synthetic estrogen diethylstilbestrol (DES) and this has been called the "DES syndrome". The developing organism is particularly sensitive to developmental exposure to estrogens inducing long-term changes in various organs including the reproductive organs. The molecular mechanism underlying the persistent vaginal changes induced by perinatal estrogen exposure was partly demonstrated. Persistent phosphorylation and sustained expression of EGF-like growth factors, lead to estrogen receptor α (ESR1) activation, and then persistent vaginal epithelial cell proliferation. Agents which are weakly estrogenic by postnatal criteria may have major developmental effects, especially during a critical perinatal period. The present review outlines various studies conducted by four generations of investigators all under the influence of Prof. Bern. The studies include reports of persistent changes induced by neonatal androgen exposure, analyses of estrogen responsive genes, factors determining epithelial differentiation in the Müllerian duct, ESR and growth factor signaling, and polyovular follicles in mammals. This review is then expanded to the studies on the effects of environmental estrogens on wildlife and endocrine disruption in Daphnids.

The development of the female reproductive tract can be divided into three parts consisting of Müllerian duct organogenesis, pre-sexual maturation organ development, and post-sexual maturation hormonal regulation. In primates, Müllerian duct organogenesis proceeds in an estrogen independent fashion based on transcriptional pathways that are suppressed in males by the presence of AMH and SRY. However, clinical experience indicates that exposure to xenoestrogens such as diethylstilbestrol (DES) during critical periods including late organogenesis and pre-sexual maturational development can have substantial effects on uterine morphology, and confer increased risk of disease states later in life. Recent evidence has demonstrated that these effects are in part due to epigenetic regulation of gene expression, both in the form of aberrant CpG methylation, and accompanying histone modifications. While xenoestrogens and selective estrogen receptor modulators (SERMS) both can induce non-canonical binding confirmations in estrogen receptors, the primate specific fetal estrogens Estriol and Estetrol may act in a similar fashion to alter gene expression through tissue specific epigenetic modulation.

Many environmental pollutants act as endocrine-disrupting compounds by inhibiting human placental 3β-hydroxysteroid dehydrogenase/Δ

Efficiency of diethylstilbestrol (DES) was evaluated for preventing unwanted pregnancy following misalliance in eight bitches of different breeds, age, and bodyweight along with use of vaginal cytology on the day of case registration for retrospective confirmation of stage of estrous cycle and time of mating. All the bitches were injected with diethylstilbestrol (DES) @ 2.0 mg/kg b. wt., i/m (Max. 20 mg) on day three and five post-mating and were subjected to blood examination on day zero and seven of DES injection. An ultra-sonographic scan was carried out in each of the bitch on day 30-35 post-mating to rule out the pregnancy status of the animal and success of therapy. All the bitches were followed up for 70-100 days post-treatment for any untoward effects. The major exfoliative cells found in vaginal cytology were of large intermediate/anuclear cells (94.37 ± 0.57 %) characteristics of a peak estrus phase, and 6 of 8 bitches also showed presence of sperm in the smear evinced mating. All the bitches were found to be non-pregnant on USG scan 30-35 days post-treatment and had no serious side effect during the follow-up period. The pre- and post-treatment mean values of hemoglobin (g/dL), WBCs (×103/?L) and RBCs (×106/?L) were 15.58 ± 0.59 vs. 15.33 ± 0.60, 9.10 ± 0.44 vs. 11.33 ± 1.60 and 6.94 ± 0.12 vs. 6.83 ± 0.22, respectively, differing non-significantly. It was concluded that the exfoliative vaginal cytology in bitches having fully cornified superficial/anuclear cells as predominant cells with sperm presence indicates misalliance during estrus phase. Injection diethylstilbestrol twice could prevent the conception and establishment of pregnancy in bitches having misalliance, with minimal effect on their health.

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Prenatal diethylstilbestrol (DES) exposure is associated with increased risk of hormonally mediated cancers and other medical conditions. We evaluated the association between DES and risk of pancreatic cancer and pancreatic disorders, type 2 diabetes, and gallbladder disease, which may be involved with this malignancy. Our analyses used follow-up data from the US National Cancer Institute DES Combined Cohort Study. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age, sex, cohort, body mass index, smoking, and alcohol for the association between prenatal DES exposure and type 2 diabetes, gallbladder disease (mainly cholelithiasis), pancreatic disorders (mainly pancreatitis), and pancreatic cancer among 5667 exposed and 3315 unexposed individuals followed from 1990 to 2017. Standardized incidence rate (SIR) ratios for pancreatic cancer were based on age-, race-, and calendar year-specific general population cancer incidence rates. In women and men combined, the hazards for total pancreatic disorders and pancreatitis were greater in the prenatally DES exposed than the unexposed (HR = 11, 95% CI 2.6–51 and HR = 7.0, 95% CI 1.5–33, respectively). DES was not associated overall with gallbladder disease (HR = 1.2, 95% CI 0.88–1.5) or diabetes (HR = 1.1, 95% CI 0.9–1.2). In women, but not in men, DES exposure was associated with increased risk of pancreatic cancer compared with the unexposed (HR: 4.1, 95% CI 0.84–20) or general population (SIR: 1.9, 95% CI 1.0–3.2). Prenatal DES exposure may increase the risk of pancreatic disorders, including pancreatitis in women and men. The data suggested elevated pancreatic cancer risk in DES-exposed women, but not in exposed men.

Purpose of review Uterine leiomyoma (fibroids) is a gynecologic disorder impacting the majority of women in the United States. When symptomatic, these noncancerous tumors can cause severe morbidity including pelvic pain, menorrhagia, and infertility. Endocrine-disrupting chemicals (EDCs) may represent a modifiable risk factor. The aim of this review is to summarize recent human and experimental evidence on EDCs exposures and fibroids. Recent findings Multiple EDCs are associated with fibroid outcomes and/or processes including phthalates, parabens, environmental phenols, alternate plasticizers, Diethylstilbestrol, organophosphate esters, and tributyltin. Epidemiologic studies suggest exposure to certain EDCs, such as di-(2-ethylhxyl)-phthalate (DEHP), are associated with increased fibroid risk and severity. Both human and experimental studies indicate that epigenetic processes may play an important role in linking EDCs to fibroid pathogenesis. In-vitro and in-vivo studies show that DEHP, bisphenol A, and diethylstilbestrol can impact biological pathways critical to fibroid pathogenesis. Summary While research on EDCs and fibroids is still evolving, recent evidence suggests EDC exposures may contribute to fibroid risk and progression. Further research is needed to examine the impacts of EDC mixtures and to identify critical biological pathways and windows of exposure. These results could open the door to new prevention strategies for fibroids.

The effect of genistein (GEN) on the gene expression level of stromal cell-derived factor-1/CXCL-12 and early growth response gene-1 was studied in ovarian tissue of young and initially ageing (early stages in the ageing process) female rats. Forty, young female Sprague Dawley (SD) rats of 2-3 months old (200 ±20 g) and forty, initially ageing female SD rats of 10-12 months (490 ± 20 g) old were selected. According to the weight, rats were divided into control group, low-dose group (L), medium-dose group (M) and a high-dose group (H) and were given 15, 30 and 60 mg/kg GEN respectively. The positive control (Oestrogen) group was given 0.5 mg/kg diethylstilbestrol. The treatment lasted for 30 days. The mRNA expression of C-X-C motif chemokine ligand 12 (CXCL-12) and early growth response factor-1 (EGR-1) was measured by real-time PCR, and protein expression of EGR-1 was detected by Western blot. When compared to the negative control group (NC), the ovary/body weight ratio in the young rats decreased in the GEN group, but the difference was not significant. Similarly, compared with NC, the ovary/body weight ratio in the initially ageing rats also decreased with the increase in GEN concentration, but the decrease was significant in M and H groups (p < .01). The administration of GEN enhanced both the gene and protein expression levels of CXCL-12 and EGR-1 in the ovary. Pearson's correlation analysis showed a synergistic effect between CXCL-12 and EGR-1. Thus, we conclude that the effect of GEN on CXCL-12 and EGR-1 in the initially ageing group was obvious than that in the younger group.

Summary Objective Prenatal exposure of women to diethylstilbestrol (DES) has been associated with reproductive tract anomalies, menstrual irregularity, infertility and pregnancy complications. In prenatally exposed men, adverse effects included genital anomalies and possible risk of infertility. In children of prenatally exposed women, i.e the third generation, an increased incidence of genital defects was observed in sons (hypospadias), but not in daughters. In daughters of prenatally exposed men, the incidence of genital anomalies was in the normal range. Experimental studies in mice evidenced an increased incidence of reproductive tract anomalies in the female descendants of females and males prenatally exposed to DES, indicative of transgenerational transmission of DES defects. The aim of this study is to assess genital tract defects, fertility and pregnancy outcome, in daughters of women and men prenatally exposed to DES. Methods In a retrospective observational analysis, 759 daughters of prenatally exposed women and men reported their genital and reproductive characteristics that were compared with those of: 1) general population in France; 2) two cohorts of daughters of exposed women reported in previous publications; 3) women prenatally exposed to DES. Results An increased incidence of uterine defects was observed, with both doubling of uterus and bicornuate and aplastic uterus which constitutes the Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS). No specific anomalies described in prenatally exposed women such as T-shape or hypoplastic uterus were reported. Infertility appeared to be in the normal range. Pregnancy outcomes of our 121 pregnancies of women born to DES exposed mothers and two other published cohorts presented inconsistent results for ectopic pregnancy, miscarriage and preterm delivery. Early and late miscarriages were higher than expected in general population in our cohort but not in the two others. Conclusion These results must be considered as preliminary, due to the small numbers of patients, limited follow-up duration after birth due to young age of the studied population, and observational methods. An important point is that the high risk of reproductive dysfunction of women prenatally exposed to DES was not observed in their daughters. There is a signal on the high incidence of uterine defects, especially aplastic uterus, and its possible link with DES exposure through epigenetic effects is discussed in our findings. Inconsistent findings regarding pregnancy outcomes in the third generation are worthy of further examination.

Purpose: To determine the effect of quercetin on bone metabolism and serum osteocalcin in osteoporotic rats. Methods: Sixty specific pathogen-free rats were randomly divided into control group, model group; high, medium and low dose quercetin groups, and diethylstilbestrol group, with 10 rats in each group. The high, middle and low dose quercetin groups were given quercetin suspension at doses of 200, 100, 50 mg/kg/day, respectively; the ethylene estradiol group was given ethylene estradiol (1.0 mg/kg/week), while control rats received ethylene estradiol at doses of 200, 100, 50 mg/kg/day. Rats in the model group were given saline. Samples were taken after 6 weeks of administration. The levels of serum bone-derived alkaline phosphatase (BALP), estradiol (E2) and serum osteocalcin (BGP) in femur tissue were measured using ELISA kits. Bone mineral density (BMD) was determined using BMD tester. Results: Relative to normal rats, BALP and BGP levels in the model rats were markedly increased, while E2 was significantly lower (p < 0.5). Quercetin treatment led to significant increases in BALP and E2 levels in the middle and high dose groups, relative to the model group, while BGP levels in all quercetin treatment groups decreased significantly, when compared to model rats (p < 0.05). There were higher BMD values in quercetin and diethylstilbestrol groups than in model (p < 0.05). Conclusion: Quercetin enhances bone formation and BMD, but decreases osteocalcin levels and maintains bone biomechanics in ovariectomized rats. Thus, it may find therapeutic application in maintaining bone health. Keywords: Quercetin, Osteoporosis, Bone metabolism, Osteocalcin

Bu çalışmada 17 β östradiol, Dietilsitilbesterol ve progesteron gibi steroid hormonların F98 glioblostomo hücre hatlarında hücre canlılığı üzerine etkilerinin araştırılması amaçlanmıştır. F98 glioblastoma hücrelerine farlı dozlarda Progesteron (10, 20, 50, 100 μM), DES (2.5, 5, 10, 20, 50, 100 μM) ve 17β estradiol (0.01, 0.1, 1, 10 μM) 24, 48 ve 72 saat süre ile uygulanmış ve hücre canlılığının belirlenmesi amacıyla MTT hücre canlılık testi uygulanmıştır. Progesteron glioblostoma hücrelerinin büyümesini doz ve zaman bağımlı olarak inhibe etmiştir. 17 β estradiol düşük dozlarda antiproliferatif etki göstermiştir. DES uygulamaları hücre canlılığı üzerinde iki yönlü etki göstermiştir. Elde edilen sonular Progesteron, 17β estradiol ve DES’in glioblostoma hücrelerinde hücre çoğalmasını inhibe ettiğini göstermektedir. Ancak bununla ilgili yolakların belirlenmesi için daha fazla çalışma yapılmasına ihtiyaç vardır., The aim of the present study is to investigate the effects of three different steroid hormones; 17 β estradiol, Diethylstilbestrol and progesterone on cell viability in F98 glioblastoma cells. F98 glioblastoma cells were treated with different concentrations of Progesterone (10, 20, 50, 100 μM), DES (2.5, 5, 10, 20, 50, 100 μM) and 17β estradiol (0.01, 0.1, 1, 10 μM)) for 24, 48 and 72 hours and MTT assay was applied to determine thecell viability. Progesterone inhibits glioblastoma cell growth in a dose and time dependent manner. Antiproliferative effect of 17 β estradiol was observed at low doses. Biphasic distribution was observed in decreasing cell viability in DES applications. These results suggest that Progesterone, 17β estradiol and DES can inhibit the proliferation of glioblastoma cells. However, further study is necessary to identify the pathways involved.Bu çalışmada 17 β östradiol, Dietilsitilbesterol veprogesterone gibi steroid hormonların F98 glioblostomo hücre hatlarında hücrecanlılığı üzerine etkilerinin araştırılması amaçlanmıştır. F98 glioblastoma hücrelerine farlıdozlarda Progesteron (10, 20, 50, 100μM), DES (2.5, 5, 10, 20, 50, 100 μM) ve 17β estradiol (0.01, 0.1, 1, 10 μM)24, 48 ve 72 saat süre ile uygulanmış ve hücre canlılığının belirlenmesiamacıyla MTT hücre canlılık testi uygulanmıştır. Progesteron glioblostomahücrelerinin büyümesini doz ve zaman bağımlı olarak inhibe etmiştir. 17 β estradiol düşük dozlardaantiproliferatif etki göstermiştir. DES uygulamaları hücre canlılığı üzerindeiki yönlü etki göstermiştir. Elde edilen sonular Progesterone, 17β estradiol ve DES’in glioblostoma hücrelerinde hücreçoğalmasını inhibe ettiğini göstermektedir. Ancak bununla ilgili yolaklarınbelirlenmesi için daha fazla çalışma yapılmasına ihtiyaç vardır.

Endocrine disrupting chemicals (EDCs) can interfere with normal hormonal action and regulation. Exposure of women to EDCs has been associated with adverse reproductive health outcomes. The assays currently used to identify EDCs that elicit female reproductive toxicity lack screening tests that address effects on the maturation of oocytes, a process that enables them to be fertilized and develop into embryos. Here, a screening method employing the bovine model of in vitro oocyte maturation and embryo production is described. Endpoints explored address important events in oocyte maturation and developmental competence acquisition. To test the method, the effects of the known human EDC diethylstilbestrol (DES; an estrogen receptor agonist) were evaluated in a range of concentrations (10–9 M, 10–7 M, 10–5 M). Bovine oocytes were exposed to DES during in vitro maturation (IVM) or embryos were exposed during in vitro embryo culture (IVC). The endpoints evaluated included nuclear maturation, mitochondrial redistribution, cumulus cell expansion, apoptosis, and steroidogenesis. DES-exposed oocytes were fertilized to record embryo cleavage and blastocyst rates to uncover effects on developmental competence. Similarly, the development of embryos exposed to DES during IVC was monitored to assess the impact on early embryo development. Exposure to 10–9 M or 10–7 M DES did not affect the endpoints addressing oocyte maturation or embryo development. However, there were considerable detrimental effects observed in oocytes exposed to 10–5 M DES. Specifically, compared to vehicle-treated oocytes, there was a statistically significant reduction in nuclear maturation (3% vs 84%), cumulus expansion (2.8-fold vs 3.6-fold) and blastocyst rate (3% vs 32%). Additionally, progesterone and pregnenolone concentrations measured in IVM culture media were increased. The screening method described here shows that bovine oocytes were sensitive to the action of this particular chemical (i.e., DES), albeit at high concentrations. In principle, this method provides a valuable tool to assess the oocyte maturation process and early embryo development that can be used for reproductive toxicity screening and possibly EDC identification. Further studies should include EDCs with different mechanisms of action and additional endpoints to further demonstrate the applicability of the bovine oocyte model for chemical risk assessment purposes and EDC identification.

Endometriosis is known to be a gynaecological condition characterised by persistent inflammation and abnormal development of endometrial stroma and glands. Researchers require a rodent model to analyse the disease environment. Animal models are the best option for investigating the etiology and effective treatment of debilitating illnesses in women since rodents, like humans, menstruate. In order to develop the model system, diethylstilbestrol (DES) was examined for its ability to induce endometriosis in rats by investigating its effect on the estrus cycle, hormones, and key markers. The results demonstrated that animals given DES had an erratic estrus cycle and aberrant hormone levels. Histomorphology revealed the development of an endometriosis environment with degenerative epithelium and enlarged glandular cells after DES induction. The higher levels of estrogen, progesterone, and MCP-1 were shown in the endometriosis induced animals. Endometriosis-induced groups had decreased levels of HOXA10 and HOXA11 and increased levels of VEGF and COX-2. Finally, the DES demonstrated endometriosis induction efficacy, implying that it might be a viable replacement for endometriosis induction.

The role of the alternate G protein–coupled estrogen receptor 1 (GPER1) in colorectal cancer (CRC) development and progression is unclear, not least because of conflicting clinical and experimental evidence for pro- and anti-tumorigenic activities. Here, we show that low concentrations of the estrogenic GPER1 ligands, 17β-estradiol, bisphenol A, and diethylstilbestrol cause the generation of lagging chromosomes in normal colon and CRC cell lines, which manifest in whole chromosomal instability and aneuploidy. Mechanistically, (xeno)estrogens triggered centrosome amplification by inducing centriole overduplication that leads to transient multipolar mitotic spindles, chromosome alignment defects, and mitotic laggards. Remarkably, we could demonstrate a significant role of estrogen-activated GPER1 in centrosome amplification and increased karyotype variability. Indeed, both gene-specific knockdown and inhibition of GPER1 effectively restored normal centrosome numbers and karyotype stability in cells exposed to 17β-estradiol, bisphenol A, or diethylstilbestrol. Thus, our results reveal a novel link between estrogen-activated GPER1 and the induction of key CRC-prone lesions, supporting a pivotal role of the alternate estrogen receptor in colon neoplastic transformation and tumor progression.

Conventional molecularly imprinted polymers (MIP)-based electrochemical sensors are generally susceptible to the changes of personal operation, electrode surface, and solution conditions. Herein, a ratiometric strategy was employed through introducing Cu

Millions of women and their fetuses were exposed to the toxic pregnancy drug diethylstilbestrol (DES) from the 1940s into the 1970s, a time when the medical profession had little knowledge about potential developmental consequences of fetal drug exposures. Pathological consequences of DES exposure to the pregnant mothers and their offspring are well documented, but now generational research is finding that the grandchildren of women given DES in pregnancy are also at risk. This commentary summarizes presentations on this subject from the Beyond Genes panel “Heritable Impacts of Diethylstilbestrol (DES).”

An impedimetric sensing strategy was developed for sensitively determining diethylstilbestrol (DES) based on a platform of porphyrin-containing covalent-organic framework (p-COF). The p-COF was synthesized using 5,10,15,20-tetra (4-aminophenyl) porphyrin (TAPP) and 1,3,6,8-tetrakis(4-formylphenyl) pyrene (TFPy) as building blocks via condensation reaction, for which p-COF was named as TAPP-TFPy-COF. Considering the large specific surface area (302.9 m

Diethylstilbestrol (DES) is a synthetic form of oestrogen that does not easily degrade in the environment and can be harmful to human health. Herein, the mechanism of the interaction between laccase and DES was investigated by various spectroscopic means and high-performance liquid chromatography (HPLC). The results of fluorescence experiments showed that the quenching of intrinsic fluorescence of laccase by DES was due to a static quenching, forming a binding site. According to the Förster non-radiative energy transfer theory (FRET), the action distance R

The continuous intake of diethylstilbestrol (DES) residue seriously threatens the health of consumers, so the rapid and sensitive detection of DES is helpful for timely food safety warning. In this study, a photothermal-sensing microfluidic paper-based analytical chip (PT-Chip) was developed for effectively screening of DES residue in foods. Competitive inhibition immunochromatography was introduced and the composite of black phosphorus nanosheets and gold nanoparticles (BP-Au) was used as signal indicators. Then, the test area was irradiated by an 808 nm laser and the photothermal transduction signal was recorded by a thermal imager to achieve sensitive photothermal detection. The amount of DES was obtained by analyzing the temperature change curve of test area. The PT-Chip can achieve accurate quantification of DES with a detection limit of 0.1 μg/L. And the successful determination of DES in different food samples indicating that the PT-Chip can be used as a promising detection device.

Diethylstilbestrol (DES), an endocrine disrupting chemical, has been linked to serious health problems in humans. In this work, a regenerative flexible upconversion-fluorescence biosensor was designed for the detection of DES in foodstuffs and environmental samples. Herein, amino-functionalized upconversion nanoparticles (UCNPs) were synthesized and immobilized on the surface of a flexible polydimethylsiloxane substrate, which was further modified with complementary DNA and dabcyl-labeled DES aptamer. The fluorescence resonance energy transfer (FRET) system was established for DES detection between dabcyl and UCNPs as the acceptor and donor pairs, respectively, which resulted in the quenching of the upconversion luminescence intensity. In the presence of a target, the FRET system was destroyed and upconversion fluorescence was restored due to the stronger affinity of the aptamer toward DES. The designed biosensor was also implemented in a dual-mode signal readout based on images from a smartphone and spectra from a spectrometer. Under the optimized experimental conditions, good linear relationships were achieved based on imaging (y = 53.055x + 36.175, R2 = 0.9851) and spectral data (y = 1.1582x + 1.9561, R2 = 0.9897). The designed biosensor revealed great practicability with a spiked recovery rate of 77.91-97.95% for DES detection in real environment and foodstuff samples. Furthermore, the proposed biosensor was regenerated seven times with an accuracy threshold of 80% demonstrating its durability and reusability. Thus, this biosensor is expected to be applied to point-of-care and on-site detection based on the developed portable smartphone device and android application.

This paper demonstrates the hierarchical design of functional, fibrous polymer monoliths. The monoliths are composed of conjugated microporous polymers that not only are embedded with heteroatoms but also feature fibrous yet compressible structures due to the in situ self-assembly process that occurs during the polymerization process. Therefore, the doped nitrogen atoms can allow the growth of zeolitic imidazolate framework (ZIF) nanocrystals, which causes the homogeneous encapsulation of individual fibers. The resulting hybrid monoliths exhibit enhanced physical properties as well as catalytic activity, allowing the formation of an additional coating layer via a thiol-epoxy reaction. The deliberate inclusion of template molecules during the reaction forms molecularly imprinted sites on the fibers to afford functional monoliths. As a proof of concept, the hierarchically designed materials are able to show effective recognition properties toward diethylstilbestrol, an endocrine disruptor, taking advantage of the binding sites that selectively capture the analyte molecules and the fibrous morphology that increases the accessibility of these binding sites. We envisage that the incorporation of various heteroatoms or nanocrystals will bring about the bespoke design of advanced monoliths with autonomous functions, leading to smart textile systems.

Cluster of differentiation (CD) 9 and CD81 are closely-related members of the tetraspanin family that consist of four-transmembrane domain proteins. Cd9 and Cd81 are highly expressed in breast cancer cells; however, their expression in healthy mammary glands is unclear. In this study, we performed quantitative real-time PCR to analyze the expression levels of Cd9 and Cd81. Histological techniques were employed to identify Cd9- and Cd81-expressing cells in rat mammary glands during pregnancy and lactation. It was observed that Cd9 and Cd81 were expressed in the mammary glands, and their expression levels correlated with mammary gland development. To identify cells expressing Cd9 and Cd81 in the mammary glands, we performed double immunohistochemical staining for CD9 and CD81, prolactin receptor long form, estrogen receptor alpha, or Ki67. The results showed that CD9 and CD81 were co-expressed in proliferating mammary epithelial cells. Next, we attempted to isolate CD9-positive epithelial cells from the mammary gland using pluriBead cell-separation technology based on antibody-mediated binding of cells to beads of different sizes, followed by isolation using sieves with different mesh sizes. We successfully isolated CD9-positive epithelial cells with 96.8% purity. In addition, we observed that small-interfering RNAs against Cd9 and Cd81 inhibited estrogen-induced proliferation of CD9-positive mammary epithelial cells. Our current findings may provide novel insights into the proliferation of mammary epithelial cells during pregnancy and lactation as well as in pathological processes associated with breast cancer.

Increasing concern over endocrine disrupting chemicals (EDCs) in environmental and food samples has created the demand for rapid and high throughput screening methods to evaluate their estrogenic effects. In this study, a sensitive assay based on estrogen receptor α (ERα) and gold nanoparticles (AuNPs) was established to screen EDCs and confirm the binding affinities of EDCs with ERα. ERα protein can prevent the salt-induced aggregation of AuNPs by recruiting Na+ from AuNPs. When there are EDCs as targets in the sample, the specific binding of ERα and EDCs via hydrogen bonding results in a reduction in the binding between Na+ and ERα, and then most Na+ ions bind to the AuNPs and induce their aggregation. Nine kinds of estrogen-agonist compound, 17β-estradiol (17β-E2), diethylstilbestrol (DES), hexoestrolum (HES), 17α-estradiol (17α-E2), estrone (E1), 2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), genistein, bisphenol A (BPA) and bisphenol B (BPB), were chosen as representative targets for the validation of this method. The ranking order of estrogenic potency determined by this method was DES > 17β-E2 > HES > 17α-E2 > E1 > HPTE > genistein > BPA > BPB, which was consistent with the published results. Moreover, the recoveries of the nine kinds of EDCs spiked in tap water and milk samples were all between 80.0% and 120.0%, which proved that this method can be used for the high throughput screening of these EDCs in environmental and food samples.

The review summarizes the data on the role of metabolic and repair systems in the mechanisms of therapy-related carcinogenesis and the effect of their polymorphism on the cancer development risk. The carcinogenic activity of different types of drugs, from the anticancer agents to analgesics, antipyretics, immunomodulators, hormones, natural remedies, and non-cancer drugs, is described. Possible approaches for the prevention of drug-related cancer induction at the initiation and promotion stages are discussed.

An ultrasensitive competitive electrochemical immunosensor for the quantitative detection of diethylstilbestrol (DES) was constructed by linear-sweep voltammetry. In this work, copper-based metal–o...

In order to investigate the mechanism of genistein (Gen) in the treatment of climacteric syndrome, an in vivo study was performed to investigate the beneficial effects of genistein on the expression of P450 aromatase (P450 arom) and follicle-stimulating hormone receptor (FSHR) in the mouse ovary and uterus. Fifty female ICR mice (45 ± 5g, n = 50), aged 12 months, were divided into the following five groups with 10 animals in each: blank control group (CG), low-dose genistein group (L-Gen), middle-dose genistein group (M-Gen) and high-dose genistein group (H-Gen) (received 15, 30 and 60 mg/kg of genistein, respectively), and oestrogen group (EG; received 0.5 mg/kg diethylstilbestrol). The expression levels of the FSHR protein were determined by an immunohistochemical staining method. The expression of P450 arom, Cytochrome P450 19 (CYP19) and FSHR was quantified by real-time PCR. Immunohistochemical results showed that the expression levels of the FSHR protein in the M-Gen (average stained area: 20.79) and the H-Gen (average stained area: 21.21) groups were significantly stronger than in the CG (average area was 17.24) group (p < .05). The expression levels of CYP19 mRNA and P450 arom were positively correlated with the dose of genistein. Specifically, the relative expression levels in the H-Gen and EG groups were more than 1.5 times higher than in the CG group (p < .05). Genistein played a significant role in regulating aromatase and FSHR gene expression to improve perimenopausal ovarian and uterine function.

Glucocorticoid hormone might cause intrauterine growth restriction. The glucocorticoid-metabolizing enzyme 11β-hydroxysteroid dehydrogenase 2 (HSD11B2) in the placenta eliminates excess levels of glucocorticoids during pregnancy. The aim of the current study was to define the effects of diethylstilbestrol (DES) on HSD11B2 activity in the mammalian placentas and identify its mode of action. Rat and human placental microsomal HSD11B2 were incubated with different concentrations of DES, and IC50 values were determined. The mode of action was analyzed by incubation of DES together with substrates, glucocorticoid and NAD+. DES suppressed rat and human HSD11B2 with IC50 values of 5.33 and 12.62 μM, respectively. DES was a competitive inhibitor of rat and human HSD11B2 when steroid substrates were added, while it was an uncompetitive inhibitor when cofactor NAD+ was exposed. Oral administration of DES (0.5 mg/kg) to the rat delayed the cortisol metabolism in adult female Sprague–Dawley rats, as indicated by the increases in cortisol’s elimination half-life, maximum concentration and area under the curve. In conclusion, DES is a potent HSD11B2 inhibitor, possibly contributing to the intrauterine growth restriction.

Hypospadias, a developmental defect of the penis, is one of the most common congenital malformations in humans. Its incidence has rapidly increased over recent decades, and this has been largely attributed to our increased exposure to endocrine-disrupting chemicals. Penis development is primarily an androgen-driven process; however, estrogen and xenoestrogens are known to affect penis development in both humans and mice. Here, we investigated the role of estrogen in the developing penis. Using a novel penis culture system, we showed that exogenous estrogen directly targets the developing penis in utero to cause hypospadias. In addition, we also uncovered an unexpected endogenous role for estrogen in normal postnatal penis development and showed that a loss of estrogen signaling results in a mild hypospadias phenotype, the most common manifestation of this disease in humans. Our findings demonstrated that both androgen and estrogen signaling are intrinsically required for normal urethral closure. These findings confirmed that penis development is not an entirely androgen-driven process but one in which endogenous estrogen signaling also plays a critical role.—Govers, L. C., Phillips, T. R., Mattiske, D. M., Rashoo, N., Black, J. R., Sinclair, A., Baskin, L. S., Risbridger, G. P., Pask, A. J. A critical role for estrogen signaling in penis development.

It is now established that diethylstilbestrol (DES) has damaging effects on the male reproductive system. However, to date there have been no studies morphological analysis of adult rat testes upon treatment with DES. Here, we examined whether DES has any significant morphological effect on steroidogenesis and spermatogenesis. DES was injected subcutaneously at 3 μg/day and 30 μg/day in adult male Sprague-Dawley (SD) rats for two different treatment lengths (1 or 3 weeks), after which rats were necropsied. TUNEL labeling, cell counting, and morphological analysis were used to evaluate the effects of DES. A high dose of DES and longer exposure severely affected the cellular development of the testis. Specifically, DES treatment disrupted both steroidogenesis and spermatogenesis by decreasing the number of spermatogonia, Sertoli cells, and Leydig cells in a dose- and time-dependent manner. Thus, DES may account for decreases in the number of spermatogenic cells, Sertoli cells and Leydig cells, which in turn may lead to reduced fertility in males.

Both membrane and nuclear fractions of estrogen receptor 1 (ESR1) mediate 17β-estradiol (E2) actions. Mice expressing nuclear (n)ESR1 but lacking membrane (m)ESR1 (nuclear-only estrogen receptor 1 [NOER] mice) show reduced E2 responsivity and reproductive abnormalities culminating in adult male and female infertility. Using this model, we investigated whether reproductive pathologies caused by the synthetic estrogen diethylstilbestrol (DES) are mitigated by mESR1 ablation. Homozygous and heterozygous wild-type (WT and HET, respectively) and NOER male and female mice were subcutaneously injected with DES (1 mg/kg body weight [BW]) or vehicle daily from postnatal day (PND) 1–5. Uterine histology was assessed in select DES-treated females at PND 5, whereas others were ovariectomized at PND 60 and treated with E2 (10 μg/kg BW) or vehicle 2 weeks later. Neonatal DES exposure resulted in ovary-independent epithelial proliferation in the vagina and uterus of WT but not NOER females. Neonatal DES treatment also induced ovary-independent adult expression of classical E2-induced transcripts (e.g., lactoferrin [Ltf] and enhancer of zeste homolog 2 [Ezh2]) in WT but not NOER mice. At PND 90, DES-treated WT and HET males showed smaller testes and a high incidence of bacterial pyogranulomatous inflammation encompassing the testes, epididymis and occasionally the ductus deferens with spread to lumbar lymph nodes; such changes were largely absent in NOER males. Results indicate that male and female NOER mice are protected from deleterious effects of neonatal DES, and thus mESR1 signaling is required for adult manifestation of DES-induced reproductive pathologies in both sexes.

Molecularly imprinted silica layers coated to quantum dots (MIP-QDs) were successfully fabricated and applied as the fluorescence probe for highly selective and sensitive determination of diethylstilbestrol (DES). Scanning electron microscopy, Transmission electron microscopy, and Fourier transform infrared spectroscopy indicated successful grafting of molecularly imprinted silica layers onto the surface of QDs. Furthermore, the fluorescence assay based on the MIP-QDs showed excellent selectivity and fluorescence quenching capability in optimal conditions and a good linear relationship was obtained in the range of 2.0 × 10−4–10.0 mg/L with a correlation coefficient of 0.9980. The limit of detection of 5.9 × 10−5 mg/L was acquired. Good recoveries ranging from 95.5% to 107.5% were achieved with relative standard deviations (RSD) below 8.4% for seawater and river water samples. The fabricated MIP-QDs were successfully employed as the recognition and response element of an microtitration 96-well fluorescence detection system. Good recoveries ranging from 82.9% to 102.0% with RSDs below 10.0% were obtained for seawater and river water samples. Results demonstrate that simple, rapid, and sensitive DES determination method based on MIP-QDs can be successfully applied to DES residue detection in seawater and river water samples.

Crystal structures exist for human, but not rodent, estrogen receptor-α ligand-binding domain (ERα-LBD). Consequently, rodent studies involving binding of compounds to ERα-LBD are limited in their molecular-level interpretation and extrapolation to humans. Because the sequences of rodent and human ERα-LBDs are >95% identical, we expected their 3D structures and ligand binding to be highly similar. To test this hypothesis, we used the human ERα-LBD structure (PDB 3UUD ) as a template to produce rat and mouse homology models. Employing the rodent models and human structure, we generated docking poses of 23 Group A ligands (17β-estradiol, diethylstilbestrol, and 21 paraben analogs) in AutoDock Vina for interspecies comparisons. Ligand RMSDs (A) (median, 95% CI) were 0.49 (0.21–1.82) (human-mouse) and 1.19 (0.22–1.82) (human-rat), well below the 2.0–2.5 A range for equivalent docking poses. Numbers of interspecies ligand-receptor residue contacts were highly similar, with Sorensen Sc (%) = 96.8 (90.0–100) (human-mouse) and 97.7 (89.5–100) (human-rat). Likewise, numbers of interspecies ligand-receptor residue contacts were highly correlated: Pearson r = 0.913 (human-mouse) and 0.925 (human-rat). Numbers of interspecies ligand-receptor atom contacts were even more tightly correlated: r = 0.979 (human-mouse) and 0.986 (human-rat). Pyramid plots of numbers of ligand-receptor atom contacts by residue exhibited high interspecies symmetry and had Spearman rs = 0.977 (human-mouse) and 0.966 (human-rat). Group B ligands included 15 ring-substituted parabens recently shown experimentally to exhibit decreased binding to human ERα and to exert increased antimicrobial activity. Ligand efficiencies calculated from docking ligands into human ERα-LBD were well correlated with those derived from published experimental data (Pearson partial rp = 0.894 and 0.918; Groups A and B, respectively). Overall, the results indicate that our constructed rodent ERα-LBDs interact with ligands in like manner to the human receptor, thus providing a high level of confidence in extrapolations of rodent to human ligand-receptor interactions.

BACKGROUND Diethylstilbestrol (DES) residues are harmful to human health because of their potential carcinogenic properties. Therefore, it is important to develop a fast and efficient pretreatment method to prevent their harmful effects on human health and the environment. RESULTS In this paper, two types of magnetic molecularly imprinted polymers (MMIPs) of DES were prepared by bulk polymerization and the sol-gel method, respectively. The synthetic materials were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy and thermogravimetric analysis. Adsorption capacities of the bulk and sol-gel MMIPs were investigated. A rapid detection method was developed using the two types of MMIPs as sorbents, coupled to high-performance liquid chromatography, for the determination of DES residues in milk samples. Under optimized conditions, the limit of detection (S/N = 3) of both methods for DES was 2.0 μg L-1 ; and the linear response range to DES was 0.1-500 mg L-1 . The milk samples were analyzed according to this method with good recoveries of 88.3-97.6 and 90.5-103.5% for the two types of MMIPs, respectively. CONCLUSIONS The method described had high sensitivity and high selectivity, and could prove to be a new method for the rapid determination of DES residues in milk samples. © 2019 Society of Chemical Industry.

Drugs taken during pregnancy can affect three generations at once: the gestating woman (F0), her exposed fetus (F1), and the fetal germ cells that confer heritable information for the grandchildren (F2). Unfortunately, despite growing evidence for connections between F0 drug exposures and F2 pathology, current approaches to risk assessment overlook this important dimension of risk. In this commentary, we argue that the unique molecular vulnerabilities of the fetal germline, particularly with regard to global epigenomic reprogramming, combined with empirical evidence for F2 effects of F1 in utero drug and other exposures, should change the way we consider potential long-term consequences of pregnancy drugs and alter toxicology's standard somatic paradigm. Specifically, we (1) suggest that pregnancy drugs common in the postwar decades should be investigated as potential contributors to the "missing heritability" of many pathologies now surging in prevalence; (2) call for inclusion of fetal germline risks in pregnancy drug safety assessment; and (3) highlight the need for intensified research to ascertain generational impacts of diethylstilbestrol, a vanguard question of human germline toxicity. Only by fully addressing this important dimension of transplacental exposure can we responsibly evaluate safety of drug exposures during pregnancy and convey the full scope of risks, while also retrospectively comprehending the generational legacy of recent history's unprecedented glut of evolutionarily novel intrauterine exposures. Environ. Mol. Mutagen. 60:445-454, 2019. © 2019 Wiley Periodicals, Inc.

Numerous chemicals have been reported to exert estrogen-like endocrine disrupting effects via a receptor binding mechanism that directly interacts with the ligand binding domain of estrogen receptor α (ERα). However, not only their binding affinities to ERα but also their interference in specific cell and tissue functions are clearly different. In this regard, significant regulation differences among three representative estrogenic chemicals (diethylstilbestrol (DES), bisphenol A (BPA), and diarylpropionitrile (DPN)), well-known ERα agonists with very similar structures, have been observed. Molecular dynamics simulation is used to explore the underlying mechanism of different regulation effects induced by the similar estrogen-like chemicals. The DES-induced 12 Å motion of the H9-H10 loop markedly expands the negative electrostatic potential surface of the AF-2 domain, which is consistent with the over-regulation effect of the agonist. In comparison, the 3 Å motion induced by BPA and DPN corresponds to the low-regulation effect of the chemicals. Cross-correlation analysis indicates that the different ERα motions and resulting surface feature of AF-2 domain are brought by the distinguished binding modes of the agonists. Moreover, only hydrophobic DES with estrogen-like size and flexibility has a high binding affinity of -23.47 kcal/mol binding free energy. Both the hydrophilic group in DPN and the small molecular size of BPA dramatically decrease the agonist binding ability, and their binding free energies are only -12.43 kcal/mol and -11.82 kcal/mol, respectively. Our study demonstrates that similar chemicals interact differently with ERα and induce different allosteric effects, which explains the observed regulation diversity.

Cyclic nucleotides (cAMP, cGMP) play a major role in normal and pathologic signaling. Beyond receptors, cyclic nucleotide phosphodiesterases; (PDEs) rapidly convert the cyclic nucleotide in its respective 5′-nucleotide to control intracellular cAMP and/or cGMP levels to maintain a normal physiological state. However, in many pathologies, dysregulations of various PDEs (PDE1-PDE11) contribute mainly to organs and tissue failures related to uncontrolled phosphorylation cascade. Among these, PDE4 represents the greatest family, since it is constituted by 4 genes with multiple variants differently distributed at tissue, cellular and subcellular levels, allowing different fine-tuned regulations. Since the 1980s, pharmaceutical companies have developed PDE4 inhibitors (PDE4-I) to overcome cardiovascular diseases. Since, they have encountered many undesired problems, (emesis), they focused their research on other PDEs. Today, increases in the knowledge of complex PDE4 regulations in various tissues and pathologies, and the evolution in drug design, resulted in a renewal of PDE4-I development. The present review describes the recent PDE4-I development targeting cardiovascular diseases, obesity, diabetes, ulcerative colitis, and Crohn’s disease, malignancies, fatty liver disease, osteoporosis, depression, as well as COVID-19. Today, the direct therapeutic approach of PDE4 is extended by developing allosteric inhibitors and protein/protein interactions allowing to act on the PDE interactome.

Endocrine disruption results from exposure to chemicals that alter the function of the endocrine system in animals. Chronic 60 days of exposure to a low dose (0.1 mu M) of ioxynil (IOX) or diethylstilbestrol (DES) via food was used to determine the effects of these chemicals on the physiology of the heart and thyroid follicles in juvenile zebrafish. Immunofluorescence analysis and subsequent 3D morphometric analysis of the zebrafish heart revealed that chronic exposure to IOX induced ventricle deformation and significant volume increase (p < 0.001). DES exposure caused a change in ventricle morphology, but volume was unaffected. Alongside, it was found that DES exposure upregulated endothelial related genes (angptl1b, mhc1lia, mybpc2a, ptgir, notch1b and vwf) involved in vascular homeostasis. Both IOX and DES exposure caused a change in thyroid follicle morphology. Notably, in IOX exposed juveniles, thyroid fol-licle hypertrophy was observed; and in DES-exposed fish, an enlarged thyroid field was present. In summary, chronic exposure of juvenile zebrafish to IOX and DES affected the heart and the thyroid. Given that both chemicals are able to change the morphology of the thyroid it indicates that they behave as endocrine disruptive chemicals (EDCs). Heart function dynamically changes thyroid morphology, and function and hence it is likely that the observed cardiac effects of IOX and DES are the source of altered thyroid status in these fish. info:eu-repo/semantics/publishedVersion

Diethylstilbestrol (DES), a transplacental endocrine-disrupting chemical, was prescribed to pregnant women for several decades. The number of women who took DES is hard to know precisely, but it has been estimated that over 10 million people have been exposed around the world. DES was classified in the year 2000 as carcinogenic to humans. The deleterious effects induced by DES are very extensive, such as abnormalities or cancers of the genital tract and breast, neurodevelopmental alterations, problems associated with socio-sexual behavior, and immune, pancreatic and cardiovascular disorders. Not only pregnant women but also their children and grandchildren have been affected. Epigenetic alterations have been detected, and intergenerational effects have been observed. More cohort follow-up studies are needed to establish if DES effects are transgenerational. Even though DES is not currently in use, its effects are still present, and families previously exposed and their later generations deserve the continuity of the research studies.

A new highly sensitive, selective, and inexpensive electrochemical method has been developed for simultaneously detecting diethylstilbestrol (DES) and 17β-estradiol (E2) in environmental samples (groundwater and lake water) using a graphite sensor modified by cerium oxide nanoparticles (CPE-CeO

Nanozyme-mediated 3,3',5,5'-tetramethylbenzidine (TMB) - H2O2 systems have spawned the establishment of multiple colorimetric sensing platforms that are effective but sometimes subject to low sensitivity. Taking temperature as the output signal, photothermal effects lead to new strategies for sensitive detection. In this paper, a colorimetric and photothermal dual-mode immunoassay for diethylstilbestrol (DES) was constructed. It is based on the oxidation reaction of TMB catalyzed by black phosphorus-gold nanoparticle (BP/Au) nanohybrids, and the kinetics as well as catalytic mechanism of the nanohybrids were investigated in detail for the first time. Herein, the nanohybrids playcatalytic and photothermal dual roles. Moreover, the one-electron oxidation product of TMB (oxidized TMB) not only acts as chromogenic agent but also an excellent NIR laser-driven photothermal agent. The temperature (ΔT/°C) was gauged by a portable digital thermometer. Through an indirect competition strategy, a simple, sensitive, and economic immunosensor was proposed. Higher DES content in the sample correlated with less BP/Au nanohybrids conjugated to the surface of ELISA microplate, a weaker color change, and a lower temperature variation when exposed to laser irradiation. This method was applied for DES determination in real samples with gratifying recovery rates, showing great promise in food safety inspection applications.

In this work, a novel electrochemiluminescence (ECL) aptasensor based on the resonance energy transfer (RET) effect between Ag3PO4-Cu-MOF (ii) and silver nanoparticles (Ag NPs) is proposed. The ECL emission spectra of Ag3PO4-Cu-MOF and the ultraviolet absorption spectra of Ag NPs showed a good spectral overlap. Based on this, we designed an "on-off-on" ECL sensing strategy for the sensitive and specific detection of diethylstilbestrol (DES). Under the optimal conditions, the linear range of the sensor for DES detection was 1.0 × 10-12-1.0 × 10-4 M, with a detection limit of 7.2 × 10-13 M (S/N = 3). The method showed simple and fast operation, high sensitivity and selectivity, a strong anti-interference ability and good stability. More importantly, the developed aptasensor exhibited excellent recognition towards residual DES in actual water samples. The sensor has superior measurement capability and potential application value in the field of environment water quality monitoring.

Introduction: Endocrine disrupting chemicals (EDCs) are chemicals that alter the actions of hormones. In the 21st Century, numerous expert groups of clinicians, scientists, and environmental activi...

Suboptimal pregnancy conditions may affect ovarian development in the fetus and be associated with early natural menopause (ENM) for offspring. A total of 106,633 premenopausal participants in Nurses’ Health Study II who provided data on their own prenatal characteristics, including diethylstilbestrol (DES) exposure, maternal cigarette smoking exposure, multiplicity, prematurity, and birth weight, were followed from 1989 to 2017. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of in utero exposures with ENM. During 1.6 million person-years of follow-up, 2,579 participants experienced ENM. In multivariable models, women with prenatal DES exposure had higher risk of ENM compared with those without it (HR = 1.33, 95% CI: 1.06, 1.67). Increased risk of ENM was observed for those with low (