Low-dose arsenic exposure disrupts rat uterine physiology independent of generation of oxidative stress

BackgroundArsenic, a major pollutant of water as well as soil, is a known endocrine disruptor, and shows adverse effects on the female reproductive physiology. However, the exact molecular events leading to reproductive dysfunctions as a result of arsenic exposure are yet to be ascertained. This report evaluates the effect and mode of action of chronic oral arsenic exposure on the uterine physiology of mature female albino rats.MethodsThe effect of chronic oral exposure to arsenic at the dose of 4 microg/ml for 28 days was evaluated on adult female albino rats. Hematoxylin-eosin double staining method evaluated the changes in the histological architecture of the uterus. Circulating levels of gonadotropins and estradiol were assayed by enzyme-linked immunosorbent assay. Expression of the estrogen receptor and estrogen-induced genes was studied at the mRNA level by RT-PCR and at the protein level by immunohistochemistry and western blot analysis.ResultsSodium arsenite treatment decreased circulating levels of estradiol in a dose and time-dependent manner, along with decrease in the levels of both LH and FSH. Histological evaluation revealed degeneration of luminal epithelial cells and endometrial glands in response to arsenic treatment, along with reduction in thickness of the longitudinal muscle layer. Concomitantly, downregulation of estrogen receptor (ER alpha), the estrogen-responsive gene - vascular endothelial growth factor (VEGF), and G1 cell cycle proteins, cyclin D1 and CDK4, was also observed.ConclusionTogether, the results indicate that arsenic disrupted the circulating levels of gonadotropins and estradiol, led to degeneration of luminal epithelial, stromal and myometrial cells of the rat uterus and downregulated the downstream components of the estrogen signaling pathway. Since development and functional maintenance of the uterus is under the influence of estradiol, arsenic-induced structural degeneration may be attributed to the reduction in circulating estradiol levels. Downregulation of the estrogen receptor and estrogen-responsive genes in response to arsenic indicates a mechanism of suppression of female reproductive functions by an environmental toxicant that is contra-mechanistic to that of estrogen.

Regeneration capability of Lin −/c-Kit +/Sca-1 + cells with or without radiation exposure for repopulation of peripheral blood in lethally irradiated mice monitored using Ly5.1 isotype on days 35, 90, and 270 after transplantation

Levels of exposure to ionizing radiation are increasing for women worldwide due to the widespread use of CT and other radiologic diagnostic modalities. Exposure to ionizing radiation as well as increased levels of estradiol and other sex hormones are acknowledged breast cancer risk factors, but the effects of whole-body radiation on serum hormone levels in cancer-free women are unknown. This study examined whether ionizing radiation exposure is associated with levels of serum hormones and other markers that may mediate radiation-associated breast cancer risk. Serum samples were measured from cancer-free women who attended biennial health examinations with a wide range of past radiation exposure levels (N = 412, ages 26-79). The women were selected as controls for separate case-control studies from a cohort of A-bomb survivors. Outcome measures included serum levels of total estradiol, bioavailable estradiol, testosterone, progesterone, prolactin, insulin-like growth factor-1 (IGF1), insulin-like growth factor-binding protein 3 (IGFBP-3), and ferritin. Relationships were assessed using repeated-measures regression models fitted with generalized estimating equations. Geometric mean serum levels of total estradiol and bioavailable estradiol increased with 1Gy of radiation dose among samples collected from postmenopausal women (17%(1Gy), 95% CI: 1%-36% and 21%(1Gy), 95% CI: 4%-40%, respectively), while they decreased in samples collected from premenopausal women (-11%(1Gy), 95% CI: -20%-1% and -12%(1Gy), 95% CI: -20%- -2%, respectively). Interactions by menopausal status were significant (P = 0.003 and P < 0.001, respectively). Testosterone levels increased with radiation dose in postmenopausal samples (30.0%(1Gy), 95% CI: 13%-49%) while they marginally decreased in premenopausal samples (-10%(1Gy), 95% CI: -19%-0%) and the interaction by menopausal status was significant (P < 0.001). Serum levels of IGF1 increased linearly with radiation dose (11%(1Gy), 95% CI: 2%-18%) and there was a significant interaction by menopausal status (P = 0.014). Radiation-associated changes in serum levels of estradiol, bioavailable estradiol, testosterone and IGF1 were modified by menopausal status at the time of collection. No associations with radiation were observed in serum levels of progesterone, prolactin, IGFBP-3 or ferritin.

ObjectiveEpidemiological studies on the association of serum oestradiol levels and inflammatory markers have reported inconsistent and conflicting results. Therefore, we investigated the association between serum oestradiol and high-sensitivity C-reactive protein (CRP) levels in women on the basis of their menopausal status.MethodsThis cross-sectional study examined the association between serum oestradiol and CRP levels on the basis of menopausal status in 151 premenopausal women aged 42.7 ± 6.7 years and 394 postmenopausal women aged 58.1 ± 6.7 years who participated in a health examination program. Multiple linear regression analysis was conducted using CRP levels as the dependent variable.ResultsMultiple linear regression analysis showed that serum oestradiol levels were inversely associated with CRP levels in premenopausal women (β coefficient = −0.298) after adjusting for age, body mass index, smoking, mean arterial pressure, and levels of fasting plasma glucose, triglycerides, high-density lipoprotein cholesterol, aspartate aminotransferase, and alanine aminotransferase. However, this association was not found in postmenopausal women after adjusting for the same confounding factors.ConclusionsSerum oestradiol levels are inversely associated with CRP levels in premenopausal women, but not in postmenopausal women. Lower oestrogenic activity may at least partly contribute to the pathogenesis of chronic inflammation, particularly in premenopausal women.

Previous studies have shown that serum estradiol (E2) levels can predict mortality in intensive care unit patients. Our study investigated the predictive role of admission estradiol level on patient mortality and development of acute kidney injury in medical intensive care unit patients with a wide range of diagnoses. We conducted a prospective cohort study using serum samples from hospitalized patients in medical, cardiac, and pulmonary intensive care units at the Ege University Hospital within 6 months. Serum estradiol levels from 118 adult patients were collected within 48h of hospitalization. Receiver operating curves and multiple logistic regression analyses were performed to investigate its relationship with acute kidney injury development and mortality. Serum estradiol levels were significantly higher in non-survivor patients than in survivor patients [85 (19-560) pg/mL vs. 32 (3-262) pg/mL, p < 0.001]. Admission estradiol levels were significantly higher in patients with AKI on admission than in patients with chronic kidney disease (p = 0.002) and normal renal function (p = 0.017). Serum E2 levels were higher in patients with renal deterioration during follow-up than patients with stable renal functions [62 (11-560) pg/mL vs. 38 (3-456) pg/mL, p = 0.004]. An admission estradiol level of 52.5pg/mL predicted follow-up renal deterioration with 63% sensitivity and 74% specificity. A combined (APACHE II-E) score using APACHE II and serum estradiol level predicted overall mortality with 66% sensitivity and 82% specificity. Admission estradiol level is a good marker to predict the development of acute kidney injury and mortality in medical intensive care unit patients.

Relationship between serum gonadal hormone levels and synkinesis in postmenopausal women and man with idiopathic facial paralysis

The article presents the results of a study to determine the expression of estrogen and progesterone receptors in glandular polyps of endometrium in women during the postmenopause. The objective: to determine expression of estrogen and progesterone receptors in glandular endometrial polyps in postmenopausal women and levels of relevant hormones in the serum. Materials and methods. A prospective analysis of 39 cases of endometrial glandular polyps and fragments of healthy endometrium, in postmenopausal women, aged 45 to 65, was conducted. Levels of progesterone and estradiol in serum were measured. Immunohistochemically determined expression of estrogen and progesterone receptors in the stroma, glands of endometrial polyps and unchanged endometrium. Results. Our data suggest that polyps have stronger expression of estrogen and progesterone receptors than glands of unchanged endometrium. Expression of estrogen receptors was determined to be superior in the stroma of polyps compared with the stroma of the endometrium. Conclusion. Our results indicate that evaluation expression of steroid receptors may be a criterion for determining the malignant potential of polyps in postmenopausal women. Key words: immunohistochemistry, hysteroscopy, estrogen and progesterone receptor, postmenopausal, polyp, endometrium.

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Disclosure: P. Gupta: None. T.B. Karatas: None. V. Tangpricha: None.Introduction/ Background: The Endocrine Society recommends that transgender individuals prescribed estradiol should have periodic measurement of serum prolactin levels due to elevated risk of hyperprolactinemia. While it is known that estradiol increases prolactin levels, the exact incidence and if there is a correlation that exists between serum prolactin and estradiol levels is not known. Specific Aim: The aim of this study was to assess incidence of prolactin elevation and any relationship between serum prolactin with serum estradiol levels in transgender individuals taking estradiol. Materials and Methods: This was a retrospective chart review. Charts were reviewed of transgender individuals receiving estradiol at a single academic medical center. Participants’ information on gender- affirming hormone therapy, use of anti-psychotics and anti- depressants, serum prolactin and estradiol levels and dates of lab draws were recorded. Linear regression analysis was used to measure the association between prolactin level and estradiol level Results: Sixty-seven (67) participants who were prescribed estradiol with at least one documented prolactin were included. A total of 103 serum prolactin and serum estradiol levels drawn at the same time were available to be analyzed. The mean age of the participants was 35.4 years (SD 13.8). The majority of the participants (38/67) were on oral 17 beta estradiol. The majority of the participants (46/67) were not on any anti-psychotics or anti-depressants. Only 6 prolactin levels (5.8%) were elevated > 20 ng/mL in 5 individuals and none were above 100 ng/mL. Only 1 out of these 5 individuals was on antipsychotics and had 2 consecutive prolactin elevations. There was no significant relationship between serum estradiol and serum prolactin levels (R= 0.18, p=0.068) on linear regression analysis.Presentation: Sunday, July 13, 2025

Ovarian aromatase cytochrome P-450 mRNA levels correlate with enzyme activity and serum estradiol levels in anestrous, pregnant and lactating rats

Objective: To observe the effects of estradiol on expression of plasma membrane Ca2+-ATPase isoform 2 in inner ear of rats. Methods: Twenty-five Three-months-old female Sprague-Dawley rats were randomly and equally divided into five groups by random number table mathod,with five rats in each group. Animals in Sham group were sham-operated while others were bilateral ovariactmized. One month after modeling, the OVX groups were supplemented with estradiol (E2 group), progesterone (P group), estradiol and progesterone (E2+P group)and vehicle sesame oil (Veh group), while the Sham operation group (Sham group) was supplemented with vehicle sesame oil.All rats were sacrificed and otocysts were obtained immediately. Enzyme-linked immunosorbent assay was used to detect the changes in serum estradiol and progesterone levels of each group of rats before operation, before treatment and before sacrifice. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression of total PMCA2 protein and mRNA in the inner ear of each group. Results: There was no significant difference in serum estradiol and progesterone levels among the five groups before operated(P>0.05). Before treatment, the serum estradiol and progesterone levels of rats in each group were significantly lower than those in Sham group (P<0.05). The serum estradiol level in E2 group and E2+P group was not significantly different from that in Sham group (P>0.05), while the serum estradiol level in P group and Veh group was significantly different from that in Sham group (P<0.05). The level of progesterone in P group and E2+P group was higher than that in Sham group (P<0.05), while the level of progesterone in Veh group and E2 group was lower than that in Sham group (P<0.05). Protein and mRNA expression of PMCA2 in P and Veh groups were significantly decreased compared with that of Sham group (P<0.05) while the expression levels underwent no significantly change in E2 and E2+P groups (P<0.05). Conclusion: The decrease of serum estradiol level can reduce the expression of otolith regulatory protein PMCA2 in rats, and then affect otolith metabolism, which may be an important link of estrogen affecting otolith metabolism.

Aim: To determine the correlation of Interleukin-6 (IL-6) with serum estradiol levels in menopausal women. Method: This research is a case series research in postmenopausal women to assess the correlation between Interleukin-6 (IL-6) and serum estradiol levels that performed at H Adam Malik General Hospital Medan, starting in August 2017 until 38 samples which met the inclusion and exclusion criteria were fulfill,using non probability sampling technique with consecutive sampling. Serum estradiol and IL-6 levels was examined, then sent to the clinical laboratory. Data tabulated to be analyzed statistically. Results: The mean serum estradiol level in menopausal women is 29.74 ± 18.69. The mean IL-6 level was 85.03 ± 33.66, in this research showed that in menopausal women there was an increase in IL-6 levels. By using the Spearman Test, the results showed that there was a significant correlation between estradiol and IL-6 with p value <0.004. Conclusion: There is a significant negative correlation between serum estradiol and IL-6 levels, which means that there is an inverse relationship between serum estradiol and IL-6 levels with weak negative strength, where decreasing estradiol does not always increase IL-6 levels.

To evaluate the relationship between estrogen receptor (ER) expression and level of serum sexual hormones in male patients with lung cancer. The levels of serum estradiol (E 2), testosterone (T), follicle stimulating hormone (FSH) and lutenising hormone (LH) were measured in 25 patients with lung cancer and 30 healthy men by enzyme immunoassay magnetic solid phase (IEMA), the ER expression was detected in 25 cancer tissues, 25 paracancerous tissues, and 11 benign pulmonary tissues by immunocytochemistry (ICC). The level of plasma E₂ in male patients with lung cancer was significantly higher than that in normal controls [(22.4±15.7) ng/L [WTBX]vs ( 12.6±4.8) ng/L, P=0.001 9] while the level of T was significantly lower while the level of T was significantly lower [(2.9±1.3) μg/L [WTBX]vs (4.1±1.5) μg/L, P= 0.003 0]. The ratio of E₂/T of male patients with lung cancer was also remarkably higher than that of control . The ratio of E₂/T of male patients with lung cancer was also remarkably higher than that of control [(9.7±10.0) ×10⁻³[WTBX]vs ( 3.4±1.6)×10⁻³, P=0.004 6]. The expression rate of ER in lung cancer tissue samples was 60.0% (15/25), but no ER expression was found in the paracancerous tissues and benign pulmonary tissues. The level of E₂ had positive correlation with the expression of ER in male patients with lung cancer (. The expression rate of ER in lung cancer tissue samples was 60.0% (15/25), but no ER expression was found in the paracancerous tissues and benign pulmonary tissues. The level of E₂ had positive correlation with the expression of ER in male patients with lung cancer (r=0.916 7, P < 0.001). There are disorders and imbalances of sexual hormone metabolism in male patients with lung cancer, and these imbalances relate to the expression of ER. The elevation of E₂ level in peripheral blood might be related to the overexpression of ER.

Arsenic is a widespread environmental toxic agent that has been shown to cause diverse tissue and cell damage and at the same time to be an effective anti-cancer therapeutic agent. The objective of this study is to explore the signaling mechanisms involved in arsenic toxicity. We show that the IkappaB kinase beta (IKKbeta) plays a crucial role in protecting cells from arsenic toxicity. Ikkbeta(-)(/)(-) mouse 3T3 fibroblasts have decreased expression of antioxidant genes, such as metallothionein 1 (Mt1). In contrast to wild type and IKKbeta-reconstituted Ikkbeta(-)(/)(-) cells, IKKbeta-null cells display a marked increase in arsenic-induced reactive oxygen species (ROS) accumulation, which leads to activation of the MKK4-c-Jun NH(2)-terminal kinase (JNK) pathway, c-Jun phosphorylation, and apoptosis. Pretreatment with the antioxidant N-acetylcysteine (NAC) and expression of MT1 in the Ikkbeta(-)(/)(-) cells prevented JNK activation; moreover, NAC pretreatment, MT1 expression, MKK4 ablation, and JNK inhibition all protected cells from death induced by arsenic. Our data show that two signaling pathways appear to be important for modulating arsenic toxicity. First, the IKK-NF-kappaB pathway is crucial for maintaining cellular metallothionein-1 levels to counteract ROS accumulation, and second, when this pathway fails, excessive ROS leads to activation of the MKK4-JNK pathway, resulting in apoptosis.

Background:Osteoporosis is a disease that is seen commonly with increasing age. The purpose of this study was to compare the bone quality of pre- and post-menopausal women using the quantitative indices determined by measurements on panoramic radiographs (mental index, inferior and superior panoramic mandibular indices, antegonion index [AGI], and gonion index) and to determine the effects of serum calcium and serum estradiol levels on alveolar bone loss.Materials and Methods:Sixty female patients in the age group of 25–55 years were included in the study. The patients were divided into three equal groups, i.e., control Group A (twenty - premenopausal women), study Group B (twenty - postmenopausal women with healthy periodontium), study Group C (twenty - postmenopausal women with periodontitis). Quantitative indices were measured on digital panoramic radiographs of the patients and serum calcium and estradiol levels were determined.Results:Correlation of serum calcium with radiomorphometric indices of all the groups showed statistically nonsignificant differences. On correlating mean estradiol levels with radiographic indices of patients of Group A and Group B showed statistically nonsignificant differences. On correlating mean estradiol levels with radiographic indices of patients of Group C patients showed statistically significant difference with positive correlation with cortical width (P = 0.04) and AGI (P = 0.02) while statistically nonsignificant correlation with other indices. The statistical tests used for the analysis of the result were one-way ANOVA, multiple comparison Tukey test, Chi-square test, Student's t-test.Conclusion:There is a little evidence of correlation of these indices with serum estradiol and calcium levels, and therefore, detailed further research about this correlation is required.