Adverse Reproductive Effects Research Articles

Magnitude and determinants of intimate partner violence against women in East Africa: multilevel analysis of recent demographic and health survey

BackgroundViolence against women is a significant public health problem, and human rights abuse, and is associated with multiple adverse physical, mental, sexual, and reproductive health effects. The current study aimed to determine the magnitude of intimate partner violence (IPV) and its determinant factors in East African countries.MethodsWe utilized the most recent demographic and health survey data from 11 East African countries, which was comprised of a weighted sample of 55,501 ever-married women. A multilevel multivariable logistic regression analysis was applied. We used an adjusted odds ratio with a 95% CI and a p value ≤ 0.05 in the multilevel logistic model to declare significant factors associated with IPV.ResultsThe overall prevalence of all forms of IPV in East African countries was 32.66% [95% CI 32.27, 33.05], with the highest IPV occurring in Uganda (14.93%) and the lowest IPV recorded in Comoros (0.87%). In the multivariable multilevel logistic regression model, women’s education, residence, sex of household head, current pregnancy, husband drinking alcohol, attitude towards wife-beating husband controlling behavior, and women’s decision-making autonomy were significantly associated with IPV.ConclusionThe risk factors noted above increase the likelihood of a woman experiencing IPV. Therefore, we recommend establishing effective health and legal response services for IPV, raising awareness of the existing legislation service and improving its application, strengthening legislations on purchasing and selling of alcohol, strengthening joint (both husband and wife) decision-making power by empowering women, improving the educational level of women, and establishing measures to break the culture of societal tolerance towards IPV.

Identifying Environmental Endocrine Disruptors Associated With the Age at Menarche by Integrating a Transcriptome-Wide Association Study With Chemical-Gene-Interaction Analysis.

Menarche is the first occurrence of menstrual bleeding and one of the most important events of female puberty. Alarmingly, over the last several decades, the mean age at menarche (AAM) has decreased. Environmental endocrine disruptors (EEDs) are chemicals that may interfere with the endocrine system, resulting in adverse developmental, immunological, neurological, and reproductive effects in humans. Thus, the effects of EEDs on fertility and reproduction are growing concerns in modern societies. In this study, we aimed to determine the influence of genetic and environmental factors on AAM. We used data from an AAM genome-wide association study of 329,345 women to conduct a transcriptome-wide association study (TWAS) with FUSION software. As references, we determined the gene-expression levels in the hypothalamus, pituitary gland, ovaries, uterus, and whole blood. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses using the significantly dysregulated genes identified by the TWAS. Using the STRING database, we also generated a protein–protein-interaction network to analyze common AAM-specific genes identified by the TWAS with different tissues. We performed chemical-related gene set enrichment analysis (CGSEA) and identified significant TWAS genes to uncover relationships between different chemicals and AAM. The TWAS identified 9,848 genes; among these, 1580 genes were significant (P < 0.05), and 11 genes were significant among the hypothalamus, pituitary, ovary, uterus, and whole blood. CGSEA identified 1,634 chemicals, including 120 chemicals significantly correlated with AAM. In summary, we performed a TWAS (for genetic factors) and CGSEA (for environmental factors) focusing on AAM and identified several AAM-associated genes and EEDs. The results of this study expand our understanding of genetic and environmental factors related to the onset of female puberty.

Protective effects oflidocaine on polycystic ovary syndrome through modulating ovarian granulosa cell physiology via PI3K/AKT/mTOR pathway.

Polycystic ovary syndrome (PCOS) is a common endocrine condition in women that causes adverse reproductive and metabolic effects. PCOS is a heterogeneous disorder and its pathogenesis is affected by different factors. Thus, the criteria for diagnosing PCOS, disease and availability of treatment options vary widely across different countries. Lidocaine has been proven to inhibit the proliferation of a variety of cancer cell types, and can be used alone or in combination with other drugs for the treatment of numerous types of disease. The present study aimed to determine whether lidocaine was able to reduce human ovarian granulosa cell tumor cell line KGN cell proliferation and provide a novel insight into potential therapeutic strategies for PCOS. KGN cells were treated alone with lidocaine at different concentrations, or with lidocaine and insulin-like growth factor-1 (IGF-1; a phosphoinositide 3-kinase (PI3K)/Protein kinase B (AKT) signaling pathway agonist) in combination for 48h. The proliferative ability of KGN cells was detected using an 3-(45)-dimethylthiahiazo (-z-y1)-35-di- phenytetrazoliumromide (MTT) assay, and cell apoptosis was detected using flow cytometry. The expression levels of proteins and mRNAs were measured using western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively. The results of the present study revealed that lidocaine significantly suppressed KGN cell proliferation and increased apoptosis. Lidocaine significantly downregulated the protein expression levels of phosphorylated (p)-AKT and p-mTOR, but had no effect on their transcriptional levels. Treatment with IGF-1, could reverse the lidocaine-induced abnormal expression of PI3K/AKT signaling pathway-related proteins. Moreover, treatment with IGF-1 could reverse all the effects of lidocaine on KGN cells. In conclusion, the findings of the present study indicated that lidocaine may inhibit KGN cell proliferation and induce apoptosis by inhibiting the activation of the PI3K/AKT/mTOR signaling pathway. These results revealed the potential inhibitory effect of lidocaine on the proliferation of KGN cells and its underlying mechanism of action, providing a novel insight into potential therapeutic strategies for PCOS.

Association of hairdressing with cancer and reproductive diseases: A systematic review.

ObjectivesTo review recent epidemiological studies investigating carcinogenic or reprotoxic effects among hairdressers who seem to be at greater risk for systemic adverse effects of chemicals released from hair care products than consumers.MethodsA systematic review according to the PRISMA‐P guidelines was performed and included studies published from 2000 to August 2021, in which cancer or adverse reproductive effects were diagnosed in 1995 and onward. Data were synthetized qualitatively due to the small number of studies, heterogeneity of study designs, outcomes, and methods.ResultsFour studies investigating cancer frequencies and six studies investigating effects on reproduction among hairdressers were identified. All were of good quality and with low risk of bias. Only one of the four studies found an increased risk of cancer reporting nine times higher odds for bladder cancer in hairdressers than the population‐based controls. Three other studies investigating bladder and lung cancer, and non‐Hodgins lymphoma did not find an increased risk in hairdressers. Regarding reprotoxic effects, numerous outcomes were investigated including menstrual disorders, congenital malformations, fetal loss, small‐for‐gestational age newborns, preterm delivery, and infertility. Increased risk was found for ventricular septal defect in newborns of fathers working as hairdressers. Furthermore, several indices of poor neonatal or maternal health were significantly associated with mothers working as hairdresser.ConclusionsDespite the scarce evidence that hairdressers are at increased risk of carcinogenic or reprotoxic effects related to their trade, such health risks cannot be ruled out. Therefore, preventive efforts to diminish occupational exposures to hairdressing chemicals should be targeted.

Organophosphate-based flame retardant (tris(1,3-dichloro-2-propyl) phosphate) reduces fecundity and impairs embryonic development in marine invertebrates

Context It is important to understand how marine invertebrates may be affected by tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), as an organophosphorus flame retardant. Aim The present research verified the hypothesis that TDCIPP would adversely affect the growth, development and reproduction of Crepidula onyx (phylum Mollusca) and Tigriopus japonicus (phylum Arthropoda). Methods Effects of chronic exposure for the whole life cycle were examined at two concentrations of TDCIPP chosen on the basis of results from preliminary range-finding test. Key results Exposure to 1 and 10 μg L−1 of TDCIPP significantly reduced larval and juvenile survival rate and shell length in C. onyx. TDCIPP caused adverse reproductive effects, including abnormal embryonic development, which led to non-viable broods and the malformation of larvae. Exposure to TDCIPP resulted in a 100-fold increase in incidence rate of abnormal larva formation. In T. japonicus, exposure to TDCIPP (10 μg L−1) resulted in non-viable broods and a significant reduction in the number of eggs and number of nauplii. Conclusions Larval survival, larval growth, fecundity, and embryonic development were identified as the TDCIPP-affected ecological endpoints in the marine invertebrate C. onyx and T. japonicus. Implications From a management perspective, these results can help us assess the ecological risk posed by TDCIPP.

Современный подход к терапии сальпингоофорита через призму новых клинических рекомендаций

Pelvic inflammatory disease (PID) is an important issue due to its high occurrence in women of reproductive age and adverse effects on reproductive function. In 2021, the Ministry of Health of the Russian Federation had approved clinical guidelines that standardized management and treatment approaches to PID. These novel clinical guidelines focus on rational outpatient antimicrobial therapy using broad-spectrum medications. Treatment is prescribed empirically considering the predominant polymicrobial nature of PID. Opportunistic microbes (i.e., obligatory and facultative anaerobes) increasingly become causative agents of PID. Low titers of these microbes are found in the normal vaginal microflora, favoring broad-spectrum antibiotics effective against gram-positive and gram-negative bacteria. Treatment duration should be at least 10–14 days to completely eradicate the pathogen and prevent chronicity. Attention should be focused on choosing antibiotics with favorable safety profiles. KEYWORDS: pelvic inflammatory disease, clinical guidelines, outpatient treatment, antibiotics, doxycycline, dispersible tablet, adherence. FOR CITATION: Selikhova M.S., Smol’yaninov A.A. State-of-the-art therapy for salpingo-oophoritis from the perspective of novel clinical guidelines. Russian Journal of Woman and Child Health. 2022;5(1):35–40 (in Russ.). DOI: 10.32364/2618-8430-2022-5-1-35-40.

“Dose-Duration Dependent Changes Induced by Atrazine in the Ovary of Adult Albino Rat and the Possible Protective Role of L-Carnitine: Histological and Immunohistochemical Study”

Introduction: Atrazine (ATR) is the most common herbicide used in the world. Several studies show that ATR has many reproductive adverse effects. L-Carnitine (LC) is a flavonoid antioxidant.Aim of the Work: The goal of this research was to elucidate the structural and biochemical alterations induced by ATR in the ovary of the adult albino rats and to clarify the possible protective role of LC. Material and Methods: 70 adult female albino rats were separated into 6 groups; Control, LC (given 100 mg LC/kg/day for 30 days), ATR sub-chronic treated (given 6.5 mg ATR/kg/day for 30 days), ATR sub-acute treated (given 65 mg/kg/day for 14 days), Sub-chronic protected (given 6.5 mg ATR/kg/day +LC 100 mg/kg/day for 30 days), and Sub-acute protected (given 65 mg ATR/kg/day +LC 100 mg/kg/day for 14 days). All doses were administrated orally. Blood and tissue samples were obtained and processed for biochemical, histological, and immunohistochemical study. Statistical analysis was also done.Results: Serum luteinizing hormone (LH) and estradiol (E2), ovarian superoxide dismutase (SOD) and catalase (CAT) significantly decreased while the ovarian malondialdehyde MDA and nitric oxide (NO) significantly increased in ATR treated groups as compared to control group. Ovarian tissue of ATR treated groups showed significant increase in number of atretic follicles and loss zona pellucida continuity in PAS stain as compared to control group. Atresia was confirmed by significant increase in immuohistochemical study of P53 in ATR treated groups. Also, there was significant decrease in mitotic division in ATR treated groups confirmed by immuohistochemical study of Ki-67 as compared to control group. Moreover, there was significant difference between the two ATR treated groups in both biochemical and structural findings. While, these changes were less obvious in protected groups after administration of LC. Conclusion: supplementation of LC could have a beneficial effect against ATR-induced ovarian damage.

Urinary trace elements in association with premature ovarian insufficiency and reproductive hormones in a Chinese population

Homeostasis disturbance of trace elements has been linked to adverse reproductive consequences, including premature ovarian insufficiency (POI) in women, but limited evidence has been reported so far. This case-control study evaluated the associations between 5 common urinary trace elements [copper (Cu), manganese (Mn), Iron (Fe), Selenium (Se), and zinc (Zn)] and the odds for POI. Urinary concentrations of these 5 metals and serum levels of POI-related reproductive hormones of 169 cases and 209 healthy controls were measured. The urinary levels of Cu and Se in women with POI were significantly higher than those in the controls. The positive associations were observed between Cu levels and the odds of POI [for the medium tertile: odds ratio (OR) = 3.79, 95% CI: 1.98–7.27, p < 0.001; for the highest tertile: OR = 3.85, 95% CI: 2.00–7.41, p < 0.001]. The highest tertile of urinary Se levels was associated with increasing POI risk (for the highest tertile: OR = 2.54, 95% CI: 1.38–4.70, compared with the lowest tertile, p for trend = 0.001). In POI patients, urinary concentrations of Zn and Fe were negatively associated with serum levels of follicle-stimulating hormone (FSH). Our findings suggested that higher exposure levels of Cu and Se might lead to an increased risk of POI.

A systematic review and meta-analysis of the impacts of glyphosate on the reproductive hormones

Worldwide use of glyphosate is constantly increasing and its residues are detected in drinking water, agriculture, and food products. There are controversial data regarding the potential reproductive adverse effects of glyphosate herbicide. Therefore, we conducted a systematic review and meta-analysis on the studies in which the alteration of at least one sexual hormone including testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol was reported as a measured outcome in rats. In November 2020, 284 articles were screened, of which eight were eligible for the meta-analysis. An overall considerable effect of glyphosate exposure was found on decreasing of testosterone (7 studies, WMD = - 1.48 ng/mL; 95% CI, - 2.34 to - 0.61; P = 0.001), LH (3 studies, WMD = - 2.03 mIu/mL; 95% CI, - 3.34 to - 0.71; P = 0.003), and FSH (3 studies, WMD = - 2.28 mIu/mL; 95% CI, - 5.12 to 0.55; P = 0.115). According to our results, glyphosate intake could have major effects on the health of reproductive system. Consequently, strict monitoring of the residual glyphosate content in the drinking water, agricultural crops, and food products is necessary.

Untargeted Metabolomics Reveals that Multiple Reproductive Toxicants are Present in the Endometrium

BACKGROUND AND AIM: Recent epidemiological research focused on the effects of environmental chemicals on the female reproductive system shows mixed results, which may be partially due to differences in exposure assessment, residual confounding from diet or lifestyle factors, or co-exposures to other chemicals. These challenges highlight the need for more precise exposure assessment at the end-organ of interest to accurately understand the adverse reproductive effects of environmental exposures. Our aim was to perform untargeted metabolomic analysis of menstrual blood, a novel biospecimen, to identify environmental toxins present in the endometrium. METHODS: Whole menstrual effluent samples were collected from four women using a menstrual cup. To evaluate the effect of sample processing times, one portion of menstrual effluent was immediately frozen at -20°C for 24hrs and the second portion was kept at 4°C for 24hrs; both samples were then stored at -80°C. Samples were analyzed using untargeted liquid chromatography with high-resolution mass spectrometry (LC-HRMS). To survey the presence of environmental exposures, LC-HRMS chemical profiles were matched to the ToxCast chemical database, which includes 4,557 commonly used commercial chemicals. Select compounds were confirmed using MS/MS and comparison to reference standards. Principal component analysis (PCA) was used to identify differences within and between individuals’ menstrual blood metabolomic profiles, and the influence of the sample processing method. RESULTS:We identified 261 high confidence matches to environmental chemicals, including suspected reproductive toxicants such as phenols, parabens, phthalates, and organochlorides. PCA showed analysis of menstrual blood samples was highly reproducible, with much higher variability between participants than between an individual’s analytical replicates. CONCLUSIONS:Our results show chemical exposures linked to reproductive toxicity and endocrine disruption are present in the endometrium. In addition, our results demonstrate that menstrual blood can be successfully collected and provides a suitable biofluid for untargeted profiling to assess environmental exposures associated with potential adverse reproductive outcomes. KEYWORDS: metabolomics, exposome, biomarkers of exposure, endocrine disrupting chemicals, reproductive outcomes

Assessment of tebuconazole exposure on bovine testicular cells and epididymal spermatozoa.

This study is the first to investigate the effects of tebuconazole (TEB) on the physiological functions of bovine testicular cells and epididymal spermatozoa. Motility and plasma membrane integrity of spermatozoa exposed to TEB (0.001-100 µM) were evaluated at different incubation times (0-6 h), while TEB-induced spermiotoxicity was assessed after 24 h in cell cultures. Testicular cells, obtained from the parenchyma of bovine testes, were seeded at 1.0 × 104 and 1.5 × 106 cells/well in 96- and 12-well culture plates and incubated for 48 h in culture media containing TEB (0.001-100 µM) to evaluate cytotoxicity and hormone release, respectively. TEB did not affect the motility and plasma membrane integrity. However, significant spermiotoxicity occurred at higher TEB (1-100 µM) concentrations (P < 0.05) compared to control and lower doses. Although no dose caused cytotoxicity in testicular cells (P > 0.05), 1 and 100 µM TEB caused a significant increase in testosterone secretion (P < 0.05). As a result, high doses of TEB (1-100 µM) had slightly suppressive effects on spermatozoa; however, these doses had stimulatory effects on testosterone secretion by testicular cells. It appears that the disruption of hormonal homeostasis of testicular cells after TEB exposure may result in metabolic and especially reproductive adverse effects in bulls.

Prevalence and factors associated with sexual violence among women aged 15–49 years in rural Uganda: evidence from the Uganda Demographic and Health Survey 2016

ObjectivesSexual violence is a serious global health problem with short- and long-term physical, mental, and reproductive adverse effects. This study aimed to determine the prevalence and factors associated with sexual violence among women of reproductive age in rural Uganda. Study designThis was a cross-sectional study based on the Uganda Demographic and Health Survey (UDHS) 2016 data. MethodsUDHS 2016 data for 5259 rural women aged 15–49 years were used in this study. Multistage stratified sampling was used to select participants, and data were collected using validated questionnaires. Multivariable logistic regression was used to determine factors associated with sexual violence. All analyses we carried out in SPSS (version 25). ResultsThe overall prevalence of sexual violence among rural women was 24.3% (95% confidence interval [CI]: 23.4–25.7) compared with 18.4% (95% CI: 17.0–20.7) among urban women. Rural women who had received only primary education had higher odds of sexual violence compared with those who had received tertiary education (adjusted odds ratio [AOR] = 3.01, 95% CI: 1.17–7.72). Women living in the Western region were more likely to experience sexual violence than those living in the Northern region of Uganda (AOR = 2.01, 95% CI: 1.41–2.87). In addition, women in the poorest wealth quintile had higher odds of sexual violence compared with those in the richest quintile (AOR = 2.06, 95% CI: 1.02–4.17). Women justifying beating, health care decision-making, and husband's/partner's frequency of getting drunk were also significantly associated with sexual violence. ConclusionsThe prevalence of sexual violence among rural Ugandan women was high and is associated with factors such as educational level, region, wealth index, justified beating, health care decision-making, and husband's/partner's frequency of getting drunk. Thus, there is a need to improve the livelihoods and income of rural women, including the promotion of continued education for girls, as well as to strengthen protective laws and policies to curb this public health issue.

A Critical Review and Scientific Prospective on Contraceptive Therapeutics from Ayurveda and Allied Ancient Knowledge.

Commonly used synthetic or prescribed hormonal drugs are known to interfere with the endocrine system and may have adverse reproductive, neurological, developmental, and metabolic effects in the body. These may also produce adverse effects such as polycystic ovarian disorder, endometriosis, early puberty, infertility or toxicity to gonads, testicular germ cell cancer, breast or prostate cancer, brain developmental problems, and even birth defects. Globally, the emergence of renewed interest in natural products for reproductive health is on the rise, which offers opportunities for new contraceptive developments. The search for alternate, safer contraceptive products or agents of natural origin is of scientific interest. Ayurvedic classical texts offer knowledge and information about the reproductive function and therapeutics including those for enhancement and limiting male and female fertility. Review of ancient, medieval, and recent—including texts on erotica that provide information on approaches and large numbers of formulations and drugs of plant, mineral or animal origin—claimed to have sterilizing, contraceptive, abortifacient, and related properties is presented. Few among these are known to be toxic and few are not so common. However, most of the formulations, ingredients, or modes of administration have remained unattended to, due to issues related to consumer compliance and limitations of standardization and lack of appropriate validation modalities. Several of these ingredients have been studied for their phytoconstituents and for the variety of pharmacological activities. Efforts to standardize several classical dosage forms and attempts to adapt to modern technologies have been made. List of formulations, ingredients, and their properties linked with known constituents, pharmacological, biological, and toxicity studies have been provided in a series of tables. The possible effectiveness and safety of selected formulations and ingredients have been examined. Suggestions based on new drug delivery systems integrated with advances in biotechnology, to provide prospects for new therapeutics for contraception, have been considered. Ayurveda is built on a holistic paradigm of biological entity rather than limited gonadal functions. Graphic presentation of a few carefully chosen possibilities has been depicted. New approaches to standardization and ethnopharmacological validation of natural contraceptive therapeutics may offer novel mechanisms and modalities and therapeutic opportunities to satisfy unmet needs of contraception.

Derivation of site-specific selenium water quality criteria: A comparison of two methods and regulatory implications.

In 2016, the US Environmental Protection Agency (USEPA) issued revised aquatic life water quality criteria for selenium (Se). The criteria ("elements") consisted of threshold concentrations applicable to fish tissue (three tissue types, though the egg and ovary tissue takes precedence over the whole-body and muscle tissue thresholds), and water column. The agency rationalized that measured concentrations of Se in fish tissue were more predictive of potential adverse reproductive effects than those measured in external media. The agency provided two mechanisms for derivation of site-specific Se water criteria: a bioaccumulation factor (BAF) approach, and a partitioning-based bioaccumulation model approach. The use of either approach assumes that fish tissue concentrations exceed one or more of the tissue criteria. We compared the two approaches using fish tissue samples from various species in the Ohio River to evaluate resulting similarities and differences in the calculated Se water quality criteria. Fish (five species) were collected near two coal-fired power plants at sites unaffected by Se from wastewater discharges. Using results for all species and all sites combined, the resulting site-specific Se criteria for the BAF and partitioning-based model approach (median values) were 2.0 and 1.5 µg/L, respectively. Considering all species, resulting criteria differed little between the two power plant locations. Resulting criteria for both methods were strongly influenced by a small (less than detection) background Se water concentration. At least for the upper Ohio River, the BAF approach (requiring less input data) seems adequate for derivation of site-specific Se water criteria. In the current study, however, none of the tissue samples exceeded USEPA's tissue criteria. Thus, the decision to derive site-specific Se water quality criteria should be evaluated on a case-by-case basis, because the process may result in either a more stringent or less stringent value, wholly dependent on local factors. Integr Environ Assess Manag 2021;17:1255-1262. © 2021 SETAC.

Genomic and Hormonal Biomarkers of Phthalate-Induced Male Rat Reproductive Developmental Toxicity Part II: A Targeted RT-qPCR Array Approach That Defines a Unique Adverse Outcome Pathway.

Previously, we demonstrated that exposure to some diortho-phthalate esters during sexual differentiation disrupts male reproductive development by reducing fetal rat testis testosterone production (T Prod) and gene expression in a dose-related manner. The objectives of the current project were to expand the number of test compounds that might reduce fetal T Prod, including phthalates, phthalate alternatives, pesticides, and drugs, and to compare reductions in T Prod with altered testis mRNA expression. We found that PEs that disrupt T Prod also reduced expression of a unique "cluster" of mRNAs for about 35 genes related to sterol transport, testosterone and insulin-like hormone 3 hormone syntheses, and lipoprotein signaling and cholesterol synthesis. However, phthalates had little or no effect on mRNA expression of genes in peroxisome proliferator-activated receptor (PPAR) pathways in the fetal liver, whereas the 3 PPAR agonists induced the expression of mRNA for multiple fetal liver PPAR pathway genes without reducing testis T Prod. In summary, phthalates that disrupt T Prod act via a novel adverse outcome pathway including down regulation of mRNA for genes involved in fetal endocrine function and cholesterol synthesis and metabolism. This profile was not displayed by PEs that did not reduce T Prod, PPAR agonists or the other chemicals. Reductions in fetal testis gene expression and T Prod in utero can be used to establish relative potency factors that can be used quantitatively to predict the doses of individual PEs and mixtures of phthalates that produce adverse reproductive tract effects in male offspring.

Immune and Nervous Systems Interaction in Endocrine Disruptors Toxicity: The Case of Atrazine.

Endocrine disruptors (ED) are natural and anthropogenic chemicals that can interfere with hormonal systems at different levels. As such, ED-induced alterations in hormone functions have been implicated in many diseases and pathological conditions, including adverse developmental, reproductive, neurological, cardiovascular, and immunological effects in mammals. The fact that ED may compete with several endogenous hormones for multiple receptors and pathways is not always fully considered. This results in a complex response that depends on the cellular context in terms of receptors and interacting proteins and, thus, may differ between tissues and circumstances. Microglia, neurons, and other immune cells are potential targets and still underappreciated actors in endocrine disruption. Due to the large scale of this topic, this review is not intended to provide a comprehensive review nor a systematic review of chemicals identified as endocrine disruptors. It focuses on the immune-neuro-endocrine network in ED toxicity and research gaps, using atrazine as an example to highlight this complexity and the interrelationship between the immune, endocrine, and nervous systems, and ED.

Plasticizers and Cardiovascular Health: Role of Adipose Tissue Dysfunction.

Since the 1950s, the production of plastics has increased 200-fold, reaching 360 million tonnes in 2019. Plasticizers, additives that modify the flexibility and rigidity of the product, are ingested as they migrate into food and beverages. Human exposure is continuous and widespread; between 75 and 97% of urine samples contain detectable levels of bisphenols and phthalates, the most common plasticizers. Concern over the toxicity of plasticizers arose in the late 1990s, largely focused around adverse developmental and reproductive effects. More recently, many studies have demonstrated that exposure to plasticizers increases the risk for obesity, type 2 diabetes, and cardiovascular disease (CVD). In the 2000s, many governments including Canada, the United States and European countries restricted the use of certain plasticizers in products targeted towards infants and children. Resultant consumer pressure motivated manufacturers to substitute plasticizers with analogues, which have been marketed as safe. However, data on the effects of these new substitutes are limited and data available to-date suggest that many exhibit similar properties to the chemicals they replaced. The adverse effects of plasticizers have largely been attributed to their endocrine disrupting properties, which modulate hormone signaling. Adipose tissue has been well-documented to be a target of the disrupting effects of both bisphenols and phthalates. Since adipose tissue function is a key determinant of cardiovascular health, adverse effects of plasticizers on adipocyte signaling and function may underlie their link to cardiovascular disease. Herein, we discuss the current evidence linking bisphenols and phthalates to obesity and CVD and consider how documented impacts of these plasticizers on adipocyte function may contribute to the development of CVD.

Heavy Load Carrying and Symptoms of Pelvic Organ Prolapse among Women in Tanzania and Nepal: An Exploratory Study.

Heavy load carrying of water, firewood, and sand/stones is a ubiquitous activity for women living in developing countries. Although the intra-abdominal pressure associated with heavy load carrying is hypothesized to increase the risk of pelvic organ prolapse (POP) among women, relevant epidemiologic data are lacking. We conducted a comparative study involving two exploratory cross-sectional studies among convenience samples of women carrying heavy loads, with different characteristics: (1) as part of their activities for daily living, in Shinyanga region, Tanzania; and (2) working as sand miners in Pokhara, Nepal. Women were categorized has having “low” or “high” load-carrying exposures based on the measured weights of the loads being carried at the time of the survey, as well as on self-reported duration and frequency of load carrying. A summary score for lower abdominal discomfort suggestive of POP was generated using questions from the Pelvic Organ Prolapse Distress Inventory (POPDI-6). Women with higher load carrying exposures had on average higher discomfort scores in both Tanzania (adjusted prevalence difference (PDa) = 3.7; 95% CI: −3.8–11.3; p = 0.33) and Nepal (PDa = 9.3; 95% CI: −4.9–23.6; p = 0.18). We identified trends suggestive of an association between increasing heavy load carrying exposures and symptoms of lower abdominal discomfort. Our findings underscore the need for larger epidemiologic studies of the potential adverse reproductive health effects of heavy load carrying activities on women in developing countries.

FOXE1 polymorphisms and chronic exposure to nitrates in drinking water cause metabolic dysfunction, thyroid abnormalities, and genotoxic damage in women.

Nitrates in drinking water has been associated to adverse health effects, including changes in glucose and lipid levels, thyroid hormone imbalance and adverse reproductive effects. We analyzed metabolic and thyroid hormone alterations and genotoxic damage in women with chronic exposure to nitrates in drinking water. The concentration of nitrates in drinking water was quantified and according to this parameter, participants were divided into three exposure scenarios. Blood and urine samples were collected from 420 women living in Durango, Mexico and biomarkers were determined. We found nitrates concentrations in drinking water above the permissible limit (>50 mg/L), and an increase in the percentage of methemoglobin (p=0.0001), nitrite in blood plasma and urine (p=0.0001), glucose (p=0.0001), total cholesterol (p=0.001), LDL (p=0.001) and triglycerides (p=0.0001). We also found alterations in TSH (p=0.01), fT3 (p=0.0003), T4T (p=0.01) and fT4 (p=0.0004) hormones. Frequency of subclinical hypothyroidism was 8.33%; differences in FOXE1 (rs965513, rs1867277) genotypes distribution were found and both polymorphisms were associated with a decrease in TSH. A high percentage of micronucleus in binucleate lymphocyte cells was found (35%, p=0.0001). In conclusion, the chronic exposure to nitrates in water for human consumption caused metabolic and hormonal alterations and genotoxic damage in women.

Simultaneous determination of a suite of endogenous steroids by LC-APPI-MS: Application to the identification of endocrine disruptors in aquatic toxicology

Exposure to endocrine-disrupting compounds (EDCs) can alter steroid hormone production in vertebrates, sometimes leading to adverse reproductive or developmental effects. Liquid chromatography mass spectrometry methods are the gold standard for analyte confirmation and quantification in biological matrices, but radioimmunoassays (RIAs) are most commonly used for measurement of select steroid hormones in aquatic toxicology studies. Existing methods for steroid quantification often employ derivatization, limiting the range of steroids that can be simultaneously measured in a single process. In the current study, a method for the simultaneous measurement of thirteen endogenous steroids in small sample volumes without derivatization using liquid chromatography atmospheric pressure photoionization tandem mass spectrometry (LC-APPI-MS/MS) was developed. Several physiologically important steroids, including 11-deoxycortisol, 11-ketotestosterone, 17α- and 17β-estradiol, 17α-hydroxyprogesterone, 17,20β-dihydroxyprogesterone, 17,20β,21-trihydroxyprogesterone, androstenedione, cortisol, estriol, estrone, progesterone, and testosterone, were selected for the analysis. The method was validated for application to small volumes of fish plasma and fish holding water. Method detection limits using only 10 µL of plasma ranged from 0.05 to 1.0 ng/mL. As a potential surrogate for plasma steroid measurements, fish holding water was analyzed to measure excreted steroids. Lower limits of quantification when using 0.25 L of water ranged from 0.05 to 1.0 ng/L. The validated method was applied to two different experiments with small fish species exposed to an EDC known to affect steroid synthesis, fadrozole. Concentrations of the 13 steroids were measured in plasma or holding water from the studies. This work demonstrates the potential application of the developed method to measure endogenous steroids for identification of EDCs in aquatic toxicology studies.