High Estrogen Concentrations Research Articles

High concentration of estrogen resulted by COH may affect the secretion of pro-angiogenic factors in uNK cells by downregulating the expression of IL-11 in decidual stromal cells.

High serum estrogen concentrations after controlled ovarian hyperstimulation (COH) and fresh embryo transfers are associated with the increased risk of pregnancy complications resulting from aberrant placentation. Uterine natural killer (uNK) cells are important for establishment of pregnancy and normal placentation. It has been found that the proliferation and function of uNK cells are compromised by COH. However, the underlying role of high concentration of estrogen following COH in the abnormalities of uNK cells is poorly understood. Expression of cytokines and immunophenotype study of uNK was performed by flow cytometry analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to quantify RNA expression; Western blot was performed to quantify protein levels. The secretion level of pro-angiogenic factors in uNK cells is significantly reduced by co-culture with decidual stromal cells (DSCs) induced by high estrogen. It was discovered that COH and supraphysiologic levels of estrogen downregulated IL-11 in decidual tissue of mice. Additionally, we found that the downregulation of IL-11 is a major factor contributing to the downregulation of VEGF and PLGF in uNK cells. Moreover, we found that uNK cells may acquire IL-11Rα sequentially during differentiation and that only a portion of uNK cells are IL-11Rα positive. Lastly, we discovered that IL-11 may regulate VEGF and PLGF secretion in uNK cells via the ERK signaling pathway. These results suggested the downregulation of IL-11 expression in DSCs caused by high estrogen levels affects the secretion of pro-angiogenic factors in uNK cells, which provided an explanation for the pregnancy complications caused by COH.

Metagenomic characterization of the equine endometrial microbiome during anestrus

The equine uterus is highly interrogated during estrus prior to breeding and establishing pregnancy. Many studies in mares have been performed during estrus under the influence of high estrogen concentrations, including the equine estrual microbiome. To date, it is unknown how the uterine microbiome of the mare is influenced by cyclicity; while, the equine vaginal microbiome is stable throughout the estrous cycle. We hypothesized that differences would exist between the equine endometrial microbiome of mares in estrus and anestrus. The aim of this study was two-fold: to characterize the resident endometrial microbiome of healthy mares during anestrus and to compare this with estrus. Double-guarded endometrial swabs were taken from healthy mares during estrus (n = 16) and in the following non-breeding season during anestrus (n = 8). Microbial population was identified using 16S rRNA sequencing. Our results suggest that the equine uterine microbiome in estrus has a low diversity and low richness, while during anestrus, a higher diversity and higher richness were seen compared to estrus. Despite this difference, both the estrus and anestrus endometrial microbiome were dominated by Proteobacteria, Firmicutes, and Bacteroidota. The composition of the microbial community between anestrus and estrus was significantly different. This may be explained by the difference in the composition of the endometrial immune milieu based on the stage of the cycle. Further research investigating the function of the equine endometrial microbiome and dynamics changes within the uterine environment is required.

Spatiotemporal variations and risk assessment of estrogens in the water of the southern Bohai Sea: A comprehensive investigation spanning three years

The ubiquitous and adverse effects of estrogens have aroused global concerns. Natural and synthetic estrogens in 255 water samples from the southern Bohai Sea were analyzed over three years. Total estrogen concentrations were 11.0–268 ng/L in river water and 1.98–99.7 ng/L in seawater, with bisphenol A (BPA) and 17α-ethynylestradiol (EE2) being the predominant estrogens, respectively. Estrogen showed the highest concentrations in summer 2018, followed by spring 2021 and spring 2019, which was consistent with the higher estrogen flux from rivers during summer. Higher estrogen concentrations in 2021 than in 2019 were driven by the higher level of BPA, an additive used in personal protective equipment. Estrogen exhibited higher concentrations in the southern coast of the Yellow River Delta and the northeastern coast of Laizhou bay due to the riverine input and aquaculture. Estrogens could disturb the normal endocrine activities of organisms and edict high ecological risks (90th simulated RQT > 1.0) to aquatic organisms, especially to fish. EE2 was the main contributor of estrogenic potency and ecological risk, which requires special concern. This is the first comprehensive study of estrogen spatiotemporal variations and risks in the Bohai Sea, providing insights into the environmental behavior of estrogens in coastal regions.

17β-estradiol induces hyperresponsiveness in guinea pig airway smooth muscle by inhibiting the plasma membrane Ca2+-ATPase

High serum estrogen concentrations are associated with asthma development and severity, suggesting a link between estradiol and airway hyperresponsiveness (AHR). 17β-estradiol (E2) has non-genomic effects via Ca2+ regulatory mechanisms; however, its effect on the plasma membrane Ca2+-ATPases (PMCA1 and 4) and sarcoplasmic reticulum Ca2+-ATPase (SERCA) is unknown. Hence, in the present study, we aim to demonstrate if E2 favors AHR by increasing intracellular Ca2+ concentrations in guinea pig airway smooth muscle (ASM) through a mechanism involving Ca2+-ATPases.In guinea pig ASM, Ca2+ microfluorometry, muscle contraction, and Western blot were evaluated. Then, we performed molecular docking analysis between the estrogens and Ca2+ ATPases.In tracheal rings, E2 produced AHR to carbachol. In guinea pig myocytes, acute exposure to physiological levels of E2 modified the transient Ca2+ peak induced by caffeine to a Ca2+ plateau. The incubation with PMCA inhibitors (lanthanum and carboxyeosin, CE) partially reversed the E2-induced sustained plateau in the caffeine response. In contrast, cyclopiazonic acid (SERCA inhibitor), U-0126 (an inhibitor of ERK 1/2), and choline chloride did not modify the Ca2+ plateau produced by E2. The mitochondrial uniporter activity and the capacitative Ca2+ entry were unaffected by E2. In guinea pig ASM, Western blot analysis demonstrated PMCA1 and PMCA4 expression. The results from the docking modeling demonstrate that E2 binds to both plasma membrane ATPases. In guinea pig tracheal smooth muscle, inhibiting the PMCA with CE, induced hyperresponsiveness to carbachol. 17β-estradiol produces hyperresponsiveness by inhibiting the PMCA in the ASM and could be one of the mechanisms responsible for the increase in asthmatic crisis in women.

Increased Expression of BCL6 in Women with Implantation Failure

Objectives: Progesterone (P4) expression failure and increased B-cell lymphoma 6 (BCL6) levels have been demonstrated in the endometrium of women withendometriosis and unexplained infertility. In the present work, we studied BCL6 (P4 inhibitor) expression in relation to different hormonal exposures of the endometrium during the implantation window, as a predictor of poor reproductive results in “in vitro fertilization” procedures. Materials and Methods: BCL6 was investigated in endometrial biopsies from four infertile patients from the Reproductive Medicine Unit, Clinicas University Hospital “José de San Martín”, Buenos Aires, Argentina, using immunohistochemical techniques. Results: Four patients without suspicion of endometriosis but recurrent implantation failure were included in the analysis. They were all evaluated during the window of implantation. Two of them were under an artificial supplemented cycle with estradiol and progesterone for a frozen thawed embryo transfer, one was under high concentrations of endogenous oestrogen and progesterone due to a controlled ovarian stimulation regimen for an assisted reproductive technique, and one had a natural menstrual cycle. All patients exceeded the threshold level of the HSCORE for BCL6 (1. 4). Conclusions: Abnormal endometrial expression of BCL6 participates in the development of P4 resistance in the endometrium. The BCL6 assay, performed prior to embryo transfer, could benefit women with suspected endometrial receptivity defects.

Comparative characteristics of healthy pregnant women and non-healthy pregnant women

We carried out a systematic search by using a literature about the issue of our interest in the PubMed and Scopus search databases. We systematically searched the literature published from December 1, 2019 to July 30, 2021 across multiple databases including PubMed, Web of Science, Google Scholar and the WHO COVID-19 database using the following keywords: “COVID-19” and “pregnancy”. Filter by date: March 1, 2020-until March 1, 2021. We have made a review of the literature on the issue of our interest in the PubMed and Scopus search databases. Based on our understanding, we want to present a small literary review. Changes in the cardiorespiratory and immune systems during pregnancy increase woman's susceptibility to severe infection and hypoxic compromise, but at the same time they may also delay diagnosis and source control in those who have only mild upper respiratory symptoms such as sore throat and nasal congestion; the latter are observed in 5% of patients with COVID-19. With gestational rhinitis, it should also be noted that in pregnant women the content of estrogen, β-estradiol increases, which increases the reactivity of the immune system. Therefore, the intensity of seizures during gestation can increase significantly. However, a high con-centration of estrogen disrupts vascular motility, causing vasomotor rhinitis during pregnancy, usually affects a fifth of healthy women in late pregnancy and leads to severe nasal congestion and rhinorrhea; these signs can mask the symptoms of COVID-19, leading to uncontrolled viral shedding and trans-mission. Dyspnea occurs in 18% of patients with COVID-19.

Endogenous estradiol contributes to vascular endothelial dysfunction in premenopausal women with type 1 diabetes

BackgroundEndogenous estrogen is cardio-protective in healthy premenopausal women. Despite this favorable action of estrogen, animal models depict a detrimental effect of estradiol on vascular function in the presence of diabetes. The present study sought to determine the role of endogenous estradiol on endothelial function in women with type 1 diabetes.Method32 women with type 1 diabetes (HbA1c = 8.6 ± 1.7%) and 25 apparently healthy women (HbA1c = 5.2 ± 0.3%) participated. Flow-mediated dilation (FMD), a bioassay of nitric-oxide bioavailability and endothelial function was performed during menses (M) and the late follicular (LF) phase of the menstrual cycle to represent low and high concentrations of estrogen, respectively. In addition, a venous blood sample was collected at each visit to determine circulating concentrations of estradiol, thiobarbituric acid reactive substances (TBARS), and nitrate/nitrite (NOx), biomarkers of oxidative stress and nitric oxide, respectively. Data were collected in (1) 9 additional women with type 1 diabetes using oral hormonal birth control (HBC) (HbA1c = 8.3 ± 2.1%) during the placebo pill week and second active pill week, and (2) a subgroup of 9 demographically matched women with type 1 diabetes not using HBC (HbA1c = 8.9 ± 2.1%).ResultsOverall, estradiol was significantly increased during the LF phase compared to M in both type 1 diabetes (Δestradiol = 75 ± 86 pg/mL) and controls (Δestradiol = 71 ± 76 pg/mL); however, an increase in TBARS was only observed in patients with type 1 diabetes (ΔTBARS = 3 ± 13 µM) compared to controls (ΔTBARS = 0 ± 4 µM). FMD was similar (p = 0.406) between groups at M. In addition, FMD increased significantly from M to the LF phase in controls (p = 0.024), whereas a decrease was observed in type 1 diabetes. FMD was greater (p = 0.015) in patients using HBC compared to those not on HBC, independent of menstrual cycle phase.ConclusionEndogenous estradiol increases oxidative stress and contributes to endothelial dysfunction in women with diabetes. Additionally, HBC use appears to be beneficial to endothelial function in type 1 diabetes.

Vaginal and vestibular electrical resistance as an alternative marker for optimum timing of artificial insemination with liquid-stored and frozen-thawed spermatozoa in sows

Development of a pen-side test to objectively determine the ideal time for artificial insemination (AI) in the sow would save producers time and money. Current processes rely on identification of oestrus via subjective behavioural and physiological markers that are indicative of high blood oestrogen concentrations. This study attempted to use measurements of electrical resistance (ER) in the cervical mucus to pinpoint timing of AI accurately enough to lead to equivalent pregnancy rates as a natural mating. Thirty-six sows were divided into 3 groups and observed for signs of oestrus. Seven sows did not show any oestrus behaviour and were excluded from the study. The remaining 29 sows were inseminated via natural mating and conventional oestrus detection (n = 14), or inseminated artificially with either liquid-stored semen (n = 8) or frozen-thawed semen (n = 7) according to timing indicated from electrical resistance measurements in the vagina and vestibule. Sows that were artificially inseminated on the basis of the electrical resistance readings had a lower pregnancy rate (P = 0.034) and less piglets born alive per litter (P < 0.05) than those that were naturally mated according to a conventional oestrus detection regime. However, the pregnancy rate and total piglets born alive did not differ between the two groups that underwent artificial insemination. Change in electrical resistance in the vagina has the potential to accurately predict ovulation timing, but more work is required to refine the timing of AI in relation to the readings before the technique can be adopted by industry.

Microbial Degradation of Free and Halogenated Estrogens in River Water-Sediment Microcosms.

Halogenated estrogens are formed during chlorine-based wastewater disinfection and have been detected in wastewater treatment plant effluent; however, very little is known about their susceptibility to biodegradation in natural waters. To better understand the biodegradation of free and halogenated estrogens in a large river under environmentally relevant conditions, we measured estrogen kinetics in aerobic microcosms containing water and sediment from the Willamette River (OR, USA) at two concentrations (50 and 1250 ng L-1). Control microcosms were used to characterize losses due to sorption and other abiotic processes, and microbial dynamics were monitored using 16S rRNA gene sequencing and ATP. We found that estrogen biodegradation occurred on timescales of hours to days and that in river water spiked at 50 ng L-1 half-lives were significantly shorter for 17β-estradiol (t1/2,bio = 42 ± 3 h) compared to its monobromo (t1/2,bio = 49 ± 5 h), dibromo (t1/2,bio = 88 ± 12 h), and dichloro (t1/2,bio = 98 ± 16 h) forms. Biodegradation was also faster in microcosms with high initial estrogen concentrations as well as those containing sediment. Free and halogenated estrone were important transformation products in both abiotic and biotic microcosms. Taken together, our findings suggest that biodegradation is a key process for removing free estrogens from surface waters but likely plays a much smaller role for the more highly photolabile halogenated forms.

Metagenomic characterization of the equine endometrial microbiome during anestrus

Recent studies have confirmed that healthy uteri, including the equine uterus, harbour a microbiome. Studies on mares have been performed in estrus and therefore under the influence of high estrogen concentrations. Multiple human studies investigating the vaginal, as well as the gut microbiome have shown that the microbiome is dynamic throughout the estrous cycle and is influenced by differences in estrogen levels. This is in contrast to a study performed on Arabian mares which indicated that the equine vaginal microbiome is stable throughout the estrous cycle.In this study the resident uterine microbiome of healthy anestrous mares was characterized by metagenomics from double-guarded endometrial swabs and compared to the microbiome in the same mares during estrus.Double guarded endometrial swabs from 15 healthy estrous mares were taken and stored at -80°C until extraction, in the following non-breeding season 8 mares from this group were sampled in similar fashion during anestrus. Blank samples were obtained during both sample period. Genomic DNA was extracted using Qiagen DNeasy PowerSoil extraction kits and 16S rRNA gene was amplified using primers 515f-806r. An amplicon sequence variant table was made and chimeras were removed and the genomic16S rRNA from the blank samples was substracted. Sequences were processed and analysed using 16S rRNA SILVA v138.1 database. Contaminating reads were removed from the samples by subtracting the reads from the blank samples using Microdecon and downstream analysis performed using the Phyloseq package. Alpha and beta diversity were calculated using microbiome, amplicon and vegan packages.Results suggest that the equine uterine microbiome in estrus has a low diversity, low richness, and a low abundance at phylum level. The equine uterine microbiome in anestrus has a higher diversity, higher richness, and higher abundance compared to the estrus uterine microbiome. However, both the estrus as well as the anestrus endometrial microbiome is dominated by Proteobacteria, Firmicutes, and Bacteroidota. PCoA analysis displays a strong dissimilarity between estrus and anestrus samples.The difference in the microbiome between estrus and anestrus can possibly be explained due to the variance in immune responsiveness of the endometrium. The estrous mare's endometrium is under the influence of estrogens, allowing for a high immune response and possibly less diverse microbiome.

Physiological Peculiarities of Puberty Period of Adolescents Whose Mothers Were Under High Risk of Terroristic Attack

INTRODUCTION: The importance of the study is determined by increasing instability of the society and involvement of civilian population in military conflicts.&#x0D; AIM: To determine peculiarities of sexual development of adolescents whose mothers experienced life-threatening stress in the period preceding pregnancy.&#x0D; MATERIALS AND METHODS: To evaluate the evidence of the secondary sexual signs, hormonal status, anthropometric data and immunity parameters, 2,980 medical records and data of preventive examinations of schoolchildren of the Republic of Dagestan were analyzed. The observation group included 1,416 schoolchildren whose mothers experienced a life-threatening mental trauma, and the control group included 1,564 adolescents whose mothers did not face life-threatening situations.&#x0D; RESULTS: The data of a comparative analysis of the regulation of physiological development of sons of women who suffered a life-threatening mental trauma, show multidirectional changes in the concentration of gonadotropic hormones with higher concentrations of estrogens, low levels of androgens, manifested by retardation of the formation of secondary sexual signs, reduced physical strength and endurance in puberty in comparison with boys of the control group. Daughters of mothers who experienced a life-threatening stress, in contrast to girls of the control group, were characterized in puberty by higher levels of luteinizing, follicle-stimulating hormones, earlier development of mammary glands and growth of pubic hair. At the same time, in transition from the prepubertal to pubertal period, these girls were characterized by earlier reduction of the activity of adrenal cortex in these girls, early menarche in the pubertal period and retardation of stabilization of the menstrual cycle rhythm.&#x0D; CONCLUSION: The adolescents being the offspring of women, who experienced a psychogenic life-threatening trauma, are characterized by disorders in physiologic maturation: boys by retardation, girls by acceleration and disharmony of the pubertal development.

Endometriosis: Update of Pathophysiology, (Epi) Genetic and Environmental Involvement.

Endometriosis is a chronic disease caused by ectopic endometrial tissue. Endometriotic implants induce inflammation, leading to chronic pain and impaired fertility. Characterized by their dependence on estradiol (via estrogen receptor β (ESRβ)) and their resistance to progesterone, endometriotic implants produce their own source of estradiol through active aromatase. Steroidogenic factor-1 (SF1) is a key transcription factor that promotes aromatase synthesis. The expression of SF1 and ESRβ is enhanced by the demethylation of their promoter in progenitor cells of the female reproductive system. High local concentrations of estrogen are involved in the chronic inflammatory environment favoring the implantation and development of endometriotic implants. Similar local conditions can promote, directly and indirectly, the appearance and development of genital cancer. Recently, certain components of the microbiota have been identified as potentially promoting a high level of estrogen in the blood. Many environmental factors are also suspected of increasing the estrogen concentration, especially prenatal exposure to estrogen-like endocrine disruptors such as DES and bisphenol A. Phthalates are also suspected of promoting endometriosis but throughmeans other than binding to estradiol receptors. The impact of dioxin or tobacco seems to be more controversial.

CHANGES IN THE VAGINAL CYTOLOGY AND PROGESTERONE AND ESTROGEN SERUM CONCENTRATIONS AFTER TREATMENT OF ANESTRTUM BITCHES WITH A COMBINATION OF FSH AND LH

The current study was designed to evaluate the changes in vaginal cytology and serum progesterone and estrogen concentration in anestrum bitches treated with a combination of FSH and LH. Seven healthy Mongrel anestrum bitches were treated with daily administration of 75 I.U. FSH plus 75 I.U LH for consecutive nine days and another three bitches were kept as a control without any treatment. Treated and control bitches were examined for the percentages of different vaginal-cytology cells, serum concentration of estrogen and progesterone, and signs of proestrus and estrus in a scheduled timeline. Five of the seven treated bitches (71.4%) showed a gradual decrease in the percentage of parabasal cells, a gradual increase in the percentage of cornified and RBCs, a rapid decrease in the estrogen concentration, and an increase in the progesterone concentration. These five bitches showed signs of proestrus and four of them showed male acceptance and were conceived. These five bitches had high estrogen concentrations before initiation of the treatment. The other two bitches had a low estrogen concentration before the initiation of the treatment and after treatment, they showed a gradual increase in the estrogen concentration, but they did not show characteristic changes in vaginal cytology or progesterone concentration. Control bitches had high estrogen concentrations before treatment, but they did not show characteristic changes in vaginal cytology, estrogen and progesterone concentrations, or signs of proestrus up to one month after the end of the treatment. In conclusion, treating anestrum bitches with a mixture of FSH and LH induced characteristic changes in vaginal cytology and serum estrogen and progesterone concentrations in the majority of bitches. These changes were associated with the induction of fertile estrus in more than half of the treated bitches, and this percentage increased to about 80% in bitches having initial high estrogen concentration. Key words: bitch; estrus-induction; FSH-LH, vaginal cytology, progesterone; estrogen

Exposure to an environmentally relevant concentration of 17α-ethinylestradiol disrupts craniofacial development of juvenile zebrafish

Endocrine disrupting chemicals (EDCs) can interact with native hormone receptors to interfere with and disrupt hormone signalling that is necessary for a broad range of developmental pathways. EDCs are pervasive in our environment, in particular in our waterways, making aquatic wildlife especially vulnerable to their effects. Many of these EDCs are able to bind to and activate oestrogen receptors, causing aberrant oestrogen signalling. Craniofacial development is an oestrogen-sensitive process, with oestrogen receptors expressed in chondrocytes during critical periods of development. Previous studies have demonstrated a negative effect of high concentrations of oestrogen on early craniofacial patterning in the aquatic model organism, the zebrafish (Danio rerio). In order to determine the impacts of exposure to an oestrogenic EDC, we exposed zebrafish larvae and juveniles to either a high concentration to replicate previous studies, or a low, environmentally relevant concentration of the oestrogenic contaminant, 17α-ethinylestradiol. The prolonged / chronic exposure regimen was used to replicate that seen by many animals in natural waterways. We observed changes to craniofacial morphology in all treatments, and most strikingly in the larvae-juveniles exposed to a low concentration of EE2. In the present study, we have demonstrated that the developmental stage at which exposure occurs can greatly impact phenotypic outcomes, and these results allow us to understand the widespread impact of oestrogenic endocrine disruptors. Given the conservation of key craniofacial development pathways across vertebrates, our model can further be applied in defining the risks of EDCs on mammalian organisms.

Recent advances in understanding adverse effects associated with drugs targeting the serotonin receptor, 5-HT GPCR.

It has been acknowledged that more women suffer from adverse effects of drugs than men globally. A group of drugs targeting serotonin [5-hydroxytryptamine] (5-HT) binding G-protein-coupled receptors (GPCRs) have been reported to preferentially affect women more than men, causing adverse effects such as breast cancer and infertility. 5-HT GPCR-targeted drugs in the central nervous system (CNS) manage psychiatric conditions, such as depression or bipolar and in the peripheral nervous system (PNS) treat migraines. Physiological characteristics such as specific types of hormones, higher body fat density and smaller body mass in women result in disparities in pharmacodynamics of drugs, thus explaining sex-related differences in the observed adverse effects. In this review, we discuss the side effects of drugs targeting 5-HT GPCRs based on serotonin's roles in the CNS and PNS. We have systematically reviewed adverse effects of drugs targeting 5-HT GPCR using information from the Food and Drug Administration and European Medicines Agency. Further information on drug side effects and receptor targets was acquired from the SIDER and DrugBank databases, respectively. These drugs bind to 5-HT GPCRs in the CNS, namely the brain, and PNS such as breasts, ovaries and testes, potentially causing side effects within these areas. Oestrogen affects both the biosynthesis of 5-HT and the densities of 5-HT GPCRs in given tissues and cells. 5-HT GPCR-targeting drugs perturb this process. This is likely a reason why women are experiencing more adverse effects than men due to their periodic increase and the relatively high concentrations of oestrogen in women and, thus a greater incidence of the oestrogen-mediated 5-HT system interference. In addition, women have a lower concentration of serotonin relative to men and also have a relatively faster rate of serotonin metabolism which might be contributing to the former. We discuss potential approaches that could mitigate at least some of the adverse effects experienced by women taking the 5-HT GPCR-targeting drugs.

Xenobiotic estradiol-17ß alters gut microbiota of hatchling American alligators (Alligator mississippiensis).

Environmental oestrogens pose serious concerns for ecosystems through their effects on organismal survival and physiology. The gut microbiome is highly vulnerable to environmental influence, yet the effects of oestrogens on gut homeostasis are unknown because they are poorly studied in wildlife populations. To determine the influence of environmental oestrogens (i.e., xenoestrogens) on the diversity and abundance of gut microbiota, we randomly assigned 23 hatchling American alligators (Alligator mississippiensis) to three ecologically relevant treatments (control, low, and high oestrogen concentrations) for 10 weeks. We predicted that xenoestrogen exposure would decrease microbial diversity and abundance within the digestive tract and that this effect would be dose-dependent. Microbial samples were collected following diet treatments and microbial diversity was determined using 16S rRNA gene-sequencing. Individuals in oestrogen-treatment groups had decreased microbial diversity, but a greater relative abundance of operational taxonomic units than those in the control group. In addition, this effect was dose-dependent; as individuals were exposed to more oestrogen, their microbiome became less diverse, less rich and less even. Findings from this study suggest that oestrogen contamination can influence wildlife populations at the internal microbial-level, which may lead to future deleterious health effects.

Fate, occurrence, and removal of estrogens in livestock wastewaters.

During the last decades, livestock and animal feeding operations have been expanded. In parallel, these activities are among the major sources of estrogens in the environment. Thus, considering the environmental and health risks associated with estrogenic compounds, this work reviews the fate, occurrence, and removal of free and conjugated E1, E2, and E3 in livestock wastewaters. A systematic literature review was carried out, and after applying the eligibility criteria, 66 peer-reviewed papers were selected. Results suggest high estrogen concentrations and, consequently, high estrogenic activity, especially in samples from swine farming. E1 and E2 are frequently found in wastewaters from bovine, swine, and other livestock effluents. Aerobic treatment processes were more efficient for estrogen removal, whereas anaerobic systems seem poorly effective. Removal efficiencies of estrogens and estrogenic activity of up to 90% were reported for constructed wetlands, advanced pond systems, trickling filters, membrane bioreactors, aerated and nitrifying reactors, combined air flotation, and vegetable oil capture processes. High concentrations found in wastewaters from livestock allied to the removal efficiencies reported for anaerobic processes (usually used to treat livestock wastewaters) evidence the importance of monitoring these compounds in environmental matrices.

Identifying areas at risk of endometrial cancer increase in Latin America: development of a geospatial model

Endometrial cancer is presently the most common gynaecological cancer in high-income countries due to factors such as population aging and obesity, which leads to high oestrogen concentrations and is linked to abnormal endometrial cell proliferation. Obesity is a global health issue; more than 20% of people in Latin America are currently obese, and approximately 58% are overweight. The purpose of this study was to analyse obesity rates and the evolution of the female population older than 65 years of age in Latin American and Caribbean countries, mapping areas at high risk of increase in the incidence of endometrial cancer in the coming years. This is an ecological study based on data on endometrial cancer incidence and mortality rates, obesity prevalence, and female population older than 65 years of age, available from the International Agency for Research on Cancer and Pan American Health Organization databases. Data were mapped individually and then combined and analysed to identify potential priority areas for intervention. Currently, Brazil, Mexico, Argentina, Cuba, and Chile are the Latin American countries with the highest endometrial cancer incidence. Puerto Rico, Uruguay, Cuba, Chile, and Argentina are those with the highest proportion of women aged 65 years or older. The highest rates of obesity are currently seen in Mexico, Argentina, Chile, and Barbados. Our analysis shows an overlap of both highest age and obesity rates in Argentina, Mexico, Barbados, and Chile. The incidence of endometrial cancer is increasing worldwide. Low-income and middle-income countries, where access to treatment can be limited, need to prepare for this rising incidence. Georeferenced information integrating available health data enables the identification of clinically vulnerable populations to further outline tailored strategies. Mexico, Argentina, Chile, and Barbados are, concurrently, in the highest quartile of obesity and proportion of women aged 65 years or older, and therefore at the greatest risk of a rising incidence of endometrial cancer in the near future. Coordinated actions to increase prevention, awareness, and health system preparedness should be taken by policy makers. None.

448 Isolation and identification of bioprospects capable of metabolizing 17-beta-estradiol and 17-alpha-ethinylestradiol using metagenomics and culture-dependent techniques in Puerto Rico

OBJECTIVES/GOALS: This research project aims to isolate and identify bioprospects capable of metabolizing estrogen using culture-dependent, culture independent methods and the identification of the gene/genes responsible for the metabolization of estrogen by the bioprospects. METHODS/STUDY POPULATION: For the culture dependent technique, samples were collected from the water treatment plant in Mayagüez, cultivated on TSA medium and selected specific and diverse colonies were patched on M-9NC (no carbon sources), M-9-glucose (M9G) and M-9-hormone mixture (M9H: 17-beta-Estradiol and 17-alpha-Ethynylestradiol). After the 48hrs incubation at 25 and 37 Celsius, growth was scored on the different media, to choose those potential bioprospects that use the hormones as the sole carbon source. For the culture independent approach, metagenomic clones from libraries generated from the Guajatacas water reservoir and Cabo Rojos Saltern microbial mats were cultivated on the appropriate M9NC, M-9G and M-9H, supplemented with Leucine and Thiamine for 48 hours at 37 Celsius. RESULTS/ANTICIPATED RESULTS: The culture-dependent approach showed a total of 6 potential bioprospects capable of growing on hormones as a sole carbon source on M9H at 25 and 37 Celsius and no-growth on the M-9 media used. Currently, we are in the process of determining the identities of the cultivable isolates genetically, any preference on hormone metabolization, monitoring a larger number of metagenomic clones and optimizing the selection conditions. DISCUSSION/SIGNIFICANCE: The identification of bioprospects capable of metabolizing hormones could potentially lead to the generation of new water treatments that could help remove unwanted chemicals, such as high concentrations of estrogens.

Metabolic and Epigenetic Regulation by Estrogen in Adipocytes.

Sex hormones contribute to differences between males and females in body fat distribution and associated disease risk. Higher concentrations of estrogens are associated with a more gynoid body shape and with more fat storage on hips and thighs rather than in visceral depots. Estrogen-mediated protection against visceral adiposity is shown in post-menopausal women with lower levels of estrogens and the reduction in central body fat observed after treatment with hormone-replacement therapy. Estrogen exerts its physiological effects via the estrogen receptors (ERα, ERβ and GPR30) in target cells, including adipocytes. Studies in mice indicate that estrogen protects against adipose inflammation and fibrosis also before the onset of obesity. The mechanisms involved in estrogen-dependent body fat distribution are incompletely understood, but involve, e.g., increased mTOR signaling and suppression of autophagy and adipogenesis/lipid storage. Estrogen plays a key role in epigenetic regulation of adipogenic genes by interacting with enzymes that remodel DNA methylation and histone tail post-translational modifications. However, more studies are needed to map the differential epigenetic effects of ER in different adipocyte subtypes, including those in subcutaneous and visceral adipose tissues. We here review recent discoveries of ER-mediated transcriptional and epigenetic regulation in adipocytes, which may explain sexual dimorphisms in body fat distribution and obesity-related disease risk.