Higher Estradiol Concentrations Research Articles

Hormonal Carcinogenesis in Canine Mammary Cancer: Molecular Mechanisms of Estradiol Involved in Malignant Progression.

Simple SummaryCanine mammary cancer corresponds to a tumor disease that frequently affects female dogs, especially those that are reproductively intact. This disease can decrease the survival and quality of life of affected animals; therefore, it is important to know the underlying mechanisms. Hormonal factors are very important for the development of this pathology. Estradiol, a hormone produced primarily in the ovaries actively participates in the process of mammary tumor formation, but the principal mechanisms behind this carcinogenic role remain incompletely understood. This review will discuss how estradiol would induce its pro-tumor effect on the mammary tissue, thus contributing to the understanding of the mechanisms involved in the development of this disease.Mammary cancer is a frequent neoplasia in female dogs, in which most important risk factors are hormonal. Sexual hormones as estradiol play an important role in mammary carcinogenesis, being able to induce carcinogenic initiation, promotion and progression. However, the molecular mechanisms involved are incompletely understood. Estradiol is synthesized mainly in the ovaries, nevertheless, high concentrations of estradiol and some of its hormonal precursors have also been described in malignant mammary tumor tissue. The mechanisms of action of estradiol include the classic genomic effects that modulate gene transcription, and non-genomic effects, which trigger quick effects after estradiol binds to its specific receptors. These responses modulate various intracellular signaling pathways, triggering post-translational modification of several proteins. This review will discuss the well-known underlying mechanisms associated with the action of estradiol in the malignant progression of canine mammary tumors.

The endocrine milieu in naturally matured follicles is different in women with high serum anti-Müllerian hormone concentrations

Research questionIs the endocrine milieu different in women with low serum anti-Müllerian hormone (AMH) concentration compared with women with high concentration? DesignCohort study of 84 women (four groups) classified according to AMH concentration and age undergoing natural cycle IVF treatment. Concentrations of LH, oestradiol, testosterone, androstenedione and AMH were determined in follicular fluid (FF), associations analysed and clinical outcome parameters evaluated. ResultsA positive correlation between serum and FF AMH concentrations was confirmed. Follicular fluid androstenedione concentration was positively correlated with serum AMH concentration (P < 0.0001, r2 = 0.197). The correlation between FF LH and FF testosterone concentration in all women was not significant (P = 0.050, r2 = 0.046); however, the correlation between FF androstenedione in women with high serum AMH concentration was significant (P = 0.032, r2 = 0.220). Follicular fluid testosterone and androstenedione were positively correlated with FF oestradiol overall and in some individual groups. The high serum AMH concentration group showed the highest FF AMH and androstenedione concentrations and lowest oestradiol–testosterone and oestradiol–androstenedione ratios. High FF AMH concentration was associated with a higher clinical pregnancy rate and high FF oestradiol concentration with a slightly better embryo quality. ConclusionsDifferences in the endocrine milieu in women with high serum AMH concentration seem to be caused by increased follicular LH concentration. In women with high serum AMH concentration, FF androstenedione is increased and ratios of oestradiol–testosterone and oestradiol–androstenedione are decreased, suggesting a disturbed endocrine milieu caused by reduced metabolization of FF androgens into oestrogens. In natural cycles, FF AMH concentrations are positively associated with higher clinical pregnancy rates and oestradiol concentrations with a higher embryo score.

Circulating sex steroids and bladder pain sensitivity in dysmenorrhea

Although elevated estradiol levels facilitate chronic pelvic pain in animal models, it remains to be determined whether sex steroid levels are altered in a cross-section of women with chronic pelvic pain (CPP) and those at-risk for developing CPP. We sought to determine if sex steroid levels are increased in women with menstrual pain and whether those changes were more extreme in two groups of women with worsened pelvic pain profiles: a) dysmenorrhea plus evidence of bladder pain sensitivity and b) bladder pain syndrome. Serum samples were collected during the mid-luteal phase to measure estradiol, progesterone, testosterone, and sex hormone-binding globulin. We also compared quantitative sensory testing profiles to evaluate how sex steroid differences influence proposed pain sensitivity mechanisms. Women with combined dysmenorrhea and bladder sensitivity had higher estradiol concentrations than controls (487 [IQR 390 - 641] vs 404 [336 - 467] pmol/L, p = 0.042). Bladder pain syndrome participants had greater sex hormone-binding globulin than controls (83 [71 - 108] vs 55 [42 - 76 nmol/L; p = 0.027). Levels of pain sensitivity and mood were different across the groups, but the only significant relationship to sex steroids was that sex hormone-binding globulin was correlated to somatic symptoms (r = 0.26, p = 0.03). These findings show women potentially at-risk for CPP and women with diagnosed CPP exhibit altered circulating levels of sex steroids. Because these hormonal differences appear to be independent of mood or pain sensitivity, the role of sex steroids in the emergence of CPP may be via sensitization of visceral afferents.

22 Comparison of vaginal microbiome and concentrations of estradiol at artificial insemination in Brangus heifers

Abstract The knowledge surrounding the bovine vaginal microbiome and its implications on fertility and reproductive traits remains incomplete. The objective of the current study was to characterize the bovine vaginal microbiome and estradiol concentrations at time of artificial insemination (AI). Brangus heifers (n = 78) underwent a 7-d Co-Synch + CIDR estrus synchronization protocol. At AI, a double guarded uterine culture swab was used to sample the anterior vaginal tract. Blood samples were collected by coccygeal venipuncture to determine concentrations of estradiol. Heifers were retrospectively classified as pregnant (n = 29) versus nonpregnant (n = 49) on day 35. Lastly, heifers were classified into low (1.1 - 2.5 pg/ml; n = 21), medium (2.6 - 6.7 pg/ml; n = 30), and high (7.2 - 17.6 pg/ml; n = 27) concentrations of estradiol. The vaginal bacterial community composition was determined through sequencing of the V4-V5 region from the 16S rRNA gene using the Illumina Miseq platform. ANOVA was used to compare the diversity metrics between treatment groups. PERMANOVA was utilized to determine variation in community structure. There were no statistical differences in the Shannon diversity index (alpha diversity; P = 0.336) or principal component analysis (beta diversity; P = 0.744) of pregnant versus nonpregnant animals. The vaginal microbiome of pregnant and nonpregnant animals was similar with the four most abundant phyla being Tenericutes, Proteobacteria, Fusobacteria, and Firmicutes. Overall bacterial community composition in animals with high, medium, or low concentrations of estradiol did not differ (P = 0.512). These results indicate that concentration of estradiol does not impact vaginal microbiome composition. In conclusion, the composition of the bovine vaginal microbiome, although dynamic, may not be directly linked to an animal’s reproductive ability.

23 Comparison of vaginal microbiome and concentrations of estradiol at artificial insemination in Brangus heifers

Abstract The knowledge surrounding the bovine vaginal microbiome and its implications on fertility and reproductive traits remains incomplete. The objective of the current study was to characterize the bovine vaginal microbiome and estradiol concentrations at time of artificial insemination (AI). Brangus heifers (n = 78) underwent a 7-day Co-Synch + CIDR estrus synchronization protocol. At AI, a double guarded uterine culture swab was used to sample the anterior vaginal tract. Blood samples were collected by coccygeal venipuncture to determine concentrations of estradiol. Heifers were retrospectively classified as pregnant (n = 29) versus nonpregnant (n = 49) on day 35. Lastly, heifers were classified into low (1.1 - 2.5 pg/ml; n = 21), medium (2.6 - 6.7 pg/ml; n = 30), and high (7.2 - 17.6 pg/ml; n = 27) concentrations of estradiol. The vaginal bacterial community composition was determined through sequencing of the V4-V5 region from the 16S rRNA gene using the Illumina Miseq platform. ANOVA was used to compare the diversity metrics between treatment groups. PERMANOVA was utilized to determine variation in community structure. There were no statistical differences in the Shannon diversity index (alpha diversity; P = 0.336) or principal component analysis (beta diversity; P = 0.744) of pregnant versus nonpregnant animals. The vaginal microbiome of pregnant and nonpregnant animals was similar with the four most abundant phyla being Tenericutes, Proteobacteria, Fusobacteria, and Firmicutes. Overall bacterial community composition in animals with high, medium, or low concentrations of estradiol did not differ (P = 0.512). These results indicate that concentration of estradiol does not impact vaginal microbiome composition. In conclusion, the composition of the bovine vaginal microbiome, although dynamic, may not be directly linked to an animal’s reproductive ability.

Association Between Visceral Adipose Tissue and Estradiol with Bone Health among Obese Women with Metabolic Syndrome

Visceral Adipose Tissue (VAT) which is associated with a higher risk of Metabolic Syndrome (MS) shows adverse effects on bone health. Moreover, MS is associated with high concentrations of serum estradiol (E2), which is essential for bone, as it inhibits bone resorption. This study aimed to investigate the impact of visceral fat and serum E2 levels on bone health markers (vitamin D, C-terminal peptide, Ca and BMD) in obese women with and without MS. This cross-sectional study was conducted on 64 obese women, with and without MS. Waist Circumference (WC) was measured in cm. Bone Mineral Density (BMD) was assessed by energy X-ray absorptiometry (DEXA), VAT was evaluated using Body Composition Analyzer "Tanita". Serum E2, C-terminal peptide and vitamin D (Vit. D) were assessed using ELISA technique. Serum calcium (Ca), triglyceride (TG), total cholesterol (Tchol), High Density Lipoproteins (HDL), Low Density Lipoproteins (LDL) and Fasting Blood Sugar (FBS) were also assessed. In women with MS, VAT showed significant positive correlations with Body Mass Index (BMI), WC and FBS. Whereas, in women without MS, VAT showed significant positive correlations with BMI, TG, age and significant negative correlation with E2. On the other hand, in women with MS, estradiol (E2) had significant negative correlation with age and significant positive correlations with BMD, BMI, FBS and body weight. While, in obese women without MS, it had significant negative correlations with Ca, VAT, age and systolic blood pressure. In obese women with MS, increased VAT, higher BMI, older age and low E2 levels have clinical significance and hence, they should be considered when predicting bone health risk.

DONOR AND RECIPIENT SEX AFFECT TRANSPLANT OUTCOMES IN AN AGE-SPECIFIC FASHION

In diseases outside of transplantation, sex has been shown to impact immune responses. Effects of donor/recipient sex and hormonal changes over a life-time on alloimmune responses and transplant outcomes have not been delineated. We analyzed SRTR data from 408,000 kidney transplant and determined the influence of recipient and donor sex in an age-specifically. Death-censored 5-year graft survival in in age-matched young female recipients (15-34 y) had been inferior to that of male recipients. This outcome was independent of donor-sex (P < 0.0001 and P = 0.0002 for male and female donors, respectively). In contrast, graft survival was superior in older female recipients (55-74 years) (P = 0.0294 and P = 0.0032 vs. male recipients of comparable age receiving either female or male kidneys). To delineate potential mechanisms, we made use of an experimental model that dissected the effects of recipient age and hormonal deprivation (ovariectomies). Skin transplants in ovariectomized young female recipients (2-3 mos) was prolonged vs. naive female and sham controls of comparable age (P = 0.0094). In contrast, graft survival was comparable in old (18 months) naïve, ovariectomized or sham control female recipients (P = 0.6798). Assessing alloimmune responses, we observed a compromised proliferation and reduced CD4+ and CD8+ T cell counts in young ovariectomized mice (CD4 + 25.2 vs 23.3 %, P = 0.0008; CD8+, 17.2 vs 12.4 %, P < 0.0001). Moreover, ovariectomies in young females reduced the production of IFN-g+ and IL-17+ by CD4+ T cells while increasing amounts of CD4+CD25+FOXP3+ regulatory T cells (P = 0.0015). When adding increased estradiol concentrations (17-b estradiol; 10-12 M and 10-10 M) in-vitro under Th1 polarizing conditions, naïve CD4+ T cells responded in a dose dependent manner (33.1 vs 35.2 %, P = 0.025). In contrast, high estradiol concentrations (10-8M reflective of levels during pregnancy) reduced amounts of CD4+ T-cells (P = 0.028, under Th1 polarizing conditions). In line, with those in-vitro findings, we observed a prolongation of graft survival when treating female recipients with pregnancy equivalent estrogen levels (sham vs treated, 9 vs 14 days, P = 0.0031). Those data demonstrate significant effects of sex, aging, and hormonal levels on alloimmune responses and transplant outcomes.

Male adiposity, sperm parameters and reproductive hormones: An updated systematic review and collaborative meta-analysis.

The present updated systematic review and meta-analysis aims to summarize the evidence from published studies with low risk for any important bias (based on methodological quality assessment) investigating the potential associations of adiposity with sperm quality and reproductive hormones. We conducted a systematic search of the literature published in MEDLINE-PubMed and EMBASE through June 2019. Based on the criteria in our review, 169 eligible publications were used for data abstraction. Finally, 60 articles were included in the qualitative analysis and 28 in the quantitative analysis. Our systematic review results indicated that overweight and/or obesity were associated with low semen quality parameters (i.e., semen volume, sperm count and concentration, sperm vitality and normal morphology) and some specific reproductive hormones (e.g., inhibin B, total testosterone and sex hormone-binding globulin). Overweight and/or obesity were also positively associated with high estradiol concentrations. Meta-analysis indicated that overweight and/or obesity categories were associated with lower sperm quality (i.e., semen volume, sperm count and concentration, sperm vitality, total motility and normal morphology), and underweight category was likewise associated with low sperm normal morphology. In conclusion, our results suggest that maintaining a healthy body weight is important for increasing sperm quality parameters and potentially male fertility.

Females’ menstrual cycle and incentive salience: Insights on neural reaction towards erotic pictures and effects of gonadal hormones

BackgroundStudies in regard to womens’ neural reactivity to erotic and other positive emotional cues in association with sexual hormones are relatively rare and findings rather inconclusive. Concerning the neural reactions towards erotic stimuli, the late positive potential (LPP) is seen as the most relevant ERP-component: More positive amplitudes are supposed to reflect larger motivational salience and higher arousal in reaction to the presented stimuli. Therefore, it was expected that the LPP in reaction to erotic pictures would be more pronounced during fertile periods of the menstrual cycle around ovulation, as well as to be associated with estradiol-levels. A similar pattern was hypothesized to be present with testosterone-levels, whereas no association with progesterone was expected. MethodN ​= ​35 free-cycling women completed an Erotic picture Stroop task (neutral, positive, and erotic stimuli, with three neutral- and three erotic subcategories) during follicular phase, ovulation and luteal phase, while EEG was recorded. Subjects provided saliva samples in order to determine estradiol-, progesterone-, and testosterone levels at each measuring time, and affective states were assessed using the Positive and Negative Affect Scale (PANAS). ResultsLPPs in reaction to erotic-compared to positive- and neutral pictures were larger in every cycle phase. LPPs in reaction to erotic couples were strongest in comparison to every other (sub-) category. During ovulation, higher estradiol-concentrations were associated with lower LPP-amplitudes towards erotic-couples- than to neutral pictures. No effects of progesterone, no direct effect of testosterone, as well as no effects of cycle phase, were evident. ConclusionResults partly contradict our hypotheses, as estradiol was expected to be positively associated with LPP during fertile stages. Possible differences between stimulus-entities (words v. pictures) and ideas for further research are being discussed.

Vaginal bacterial community composition and concentrations of estradiol at the time of artificial insemination in Brangus heifers.

The knowledge surrounding the bovine vaginal microbiota and its implications on fertility and reproductive traits remains incomplete. The objective of the current study was to characterize the bovine vaginal bacterial community and estradiol concentrations at the time of artificial insemination (AI). Brangus heifers (n = 78) underwent a 7-d Co-Synch + controlled internal drug release estrus synchronization protocol. At AI, a double-guarded uterine culture swab was used to sample the anterior vaginal tract. Immediately after swabbing the vaginal tract, blood samples were collected by coccygeal venipuncture to determine concentrations of estradiol. Heifers were retrospectively classified as pregnant (n = 29) vs. nonpregnant (n = 49) between 41 and 57 d post-AI. Additionally, heifers were classified into low (1.1 to 2.5 pg/mL; n = 21), medium (2.6 to 6.7 pg/mL; n = 30), and high (7.2 to 17.6 pg/mL; n = 27) concentration of estradiol. The vaginal bacterial community composition was determined through sequencing of the V4 region from the 16S rRNA gene using the Illumina Miseq platform. Alpha diversity was compared via ANOVA and beta diversity was compared via PERMANOVA. There were no differences in the Shannon diversity index (alpha diversity; P = 0.336) or Bray-Curtis dissimilarity (beta diversity; P = 0.744) of pregnant vs. nonpregnant heifers. Overall, bacterial community composition in heifers with high, medium, or low concentrations of estradiol did not differ (P = 0.512). While no overall compositional differences were observed, species-level differences were present within pregnancy status and estradiol concentration groups. The implications of these species-level differences are unknown, but these differences could alter the vaginal environment thereby influencing fertility and vaginal health. Therefore, species-level changes could provide better insight rather than overall microbial composition in relation to an animal's reproductive health.

High expression of estrogen receptor alpha and aromatase in glial tumor cells is associated with gender-independent survival benefits in glioblastoma patients

IntroductionGlioblastoma multiforme (GBM) is a highly malignant glial tumor, affecting men more often than women. The reason for this gender-specific predominance remains unclear, raising the question whether these effects are subject to hormonal control. The purpose of this study was to examine the expression of estrogen receptor alpha (ERα) and aromatase in human GBM tissue samples in relation to patient survival and furthermore to investigate the effect of standard chemotherapy in combination with estradiol treatment on glioblastoma tumor cell lines in vitro.Methods60 tissue samples (31 male, 29 female) of GBM patients were analysed with immunohistochemistry for ERα and aromatase for survival analyses. The cell lines LN18 and LN229 were treated with 17β-estradiol (E2) in different dosing regimens and the cell viability was measured with MTT assay. After estradiol pre-treatment Temozolomide was added and tested again.ResultsHigh expression of ERα and aromatase in the GBM tissue samples was associated with significantly longer survival times of GBM patients, regardless of gender and body-mass-index. The treatment with high concentrations of estradiol resulted in lower tumor cell viability, compared to control. The cells significantly showed a stronger sensitivity against Temozolomid (TMZ) after estradiol pre-treatment.ConclusionERα-expression of glial tumour cells seems to play an important prognostic role as a biomarker in GBM, as well as the expression of the enzyme Aromatase. The combined treatment of GBM with standard chemotherapy and estradiol may be beneficial to patient’s survival.

CHARACTERISTIC OF OVARIAN AND ESTRADIOL CONCENTRATIONS IN THE FOLLICULAR FLUID OF SLAUGHTERED ACEH CATTLE

The objective of this study was to characterize the morphology of ovary from slaughtered Aceh cow and measuring the concentration of estradiol in the follicular fluid to examine the potential utilizing for in-vitro fertilization (IVF) development in Aceh cattle. In total, 30 pairs of ovaries were collected from 30 Aceh cattle slaughtered at Banda Aceh abattoir. Morphological characteristics of ovaries observed were the size of ovaries, weight of ovaries, number of follicles, the diameter of follicles, corpus luteal (CL), and volume of follicular fluid. The follicular fluid was aspirated using a disposable syringe and analyzed the estradiol concentrations using enzyme-linked immunosorbent assay (ELISA). The follicles were grouped into 3 categories based on the diameter (Ø) of follicles: small follicles (Ø 1 - 5 mm), medium follicles (Ø 5 - 8 mm), and large follicles (Ø 8 mm). The morphological characteristic of ovaries varied between right and left ovaries in which right ovaries showed bigger size and weight compared to the left ovaries (P0.05), whereas the number of follicles and follicular fluid did not significantly different (P0.05). The concentrations of estradiol in follicular fluid of large and medium follicles were significantly higher compared to small follicles (P0.05), whereas the concentration of estradiol between large and medium follicles, did not significant different (P0.05). In conclusion, the follicles from abattoir can be used as potential oocytes resources to support IVF development for Aceh cattle in the future. The follicular fluid provided from these follicles can be an alternative for in vitro maturation media of oocytes due to containing high estradiol concentrations.

Ovarian hyperstimulation closely associated with resumption of follicular growth after chemotherapy during tamoxifen treatment in premenopausal women with breast cancer: a multicenter retrospective cohort study

BackgroundWe previously reported that tamoxifen (TAM)-induced ovarian hyperstimulation (OHS) is associated with high serum concentrations of estradiol in premenopausal women with breast cancer. To investigate risk factors for TAM-induced OHS, we performed a retrospective multicenter study.MethodsPremenopausal patients who received surgical therapy for endocrine-dependent breast cancer (n = 235) were recruited in this study and classified into 4 groups: group A, treated with TAM alone; group B, TAM treatment after 2-year-combined therapy with a gonadotropin-releasing hormone (Gn-RH) agonist; group C, TAM treatment after chemotherapy; group D, 5-year-combined therapy with TAM and a Gn-RH agonist. A serum estradiol value of more than 300 pg/mL or mean follicular diameter of more than 30 mm was defined as OHS.ResultsThe incidence of OHS in group A (n = 13/26, 50.0%) was significantly higher than those in group B (n = 17/63, 27.0%), group C (n = 20/110, 18.2%), and group D (n = 0/36, 0%). The incidence of OHS was significantly correlated with aging, and the median serum concentration of estradiol in the presence of OHS was 823.0 pg/mL. The incidence of OHS (less than 47 years old) was 62.5% in group A, 48.6% in group B, and 28.2% in group C, respectively. Notably, the incidence rate of OHS following amenorrhea in group C (n = 13/20, 65.0%) was significantly higher than that in group B (n = 1/17, 5.9%).ConclusionsThese findings indicate that the onset of OHS following amenorrhea was common in the post-chemotherapeutic group, while its ratio was low in the group after Gn-RH analog treatment, suggesting that combined treatment-based management involving TAM therapy is necessary for premenopausal patients with breast cancer.

Risk Factors for Tamoxifen-Induced Ovarian Hyperstimulation in Breast Cancer Patients

IntroductionAdjuvant endocrine therapy is an integral component of care for hormone-dependent breast cancer. Tamoxifen is a potent inducer of ovarian function and consequent hyperestrogenism in premenopausal women. However, the incidence rate and risk factors associated this phenomenon remain unclear. Patients and MethodsData of patients younger than 60 years who received adjuvant tamoxifen therapy for hormone-dependent breast cancer (stages 0-III) and who underwent regular follow-up of laboratory results for follicle-stimulating hormone and estradiol levels were retrospectively analyzed. Univariate and multivariate analyses were performed to identify clinicopathologic factors related to ovarian hyperstimulation. ResultsAmong 205 patients, 19 (9.3%) showed high values of serum estradiol during tamoxifen therapy. The mean (± SD) serum concentrations of estradiol and follicle-stimulating hormone were 1047.97 ± 638.8 pg/mL and 11.5 ± 7.3 mIU/mL, respectively. A mean of 400.83 days elapsed from the start of the single administration of tamoxifen to the initial detection of a high concentration of estradiol. Univariate and multivariate analyses showed that younger age (< 40 years) and only endocrine therapy without chemotherapy were significantly related to a higher prevalence of ovarian hyperstimulation (P = .015, relative risk = 7.49 for age < 40 years; P = .017, relative risk = 32.9 for no chemotherapy). Pathologic stages and tumor characteristics were not related to the manifestation of ovarian hyperstimulation. ConclusionYoung age (< 40 years) and endocrine treatment without chemotherapy were risk factors for the incidence of ovarian hyperstimulation during tamoxifen treatment. Close monitoring of endocrine parameters during treatment with tamoxifen especially in this patient group is essential.

Variability of serum reproductive hormones in cows presenting various reproductive conditions in semi-arid areas of the North West Province, South Africa.

Background and Aim:Hormones play a significant role in supporting reproductive processes. Predisposition to metabolic disorders may result from biological alterations in the neurohormonal system, thus leading to impaired immune function and poor reproductive performance. The aim of this study was to determine the reproductive hormonal profile in cows with reproductive conditions in semi-arid areas of the North West Province, South Africa, to establish possible correlations between different conditions and the hormonal profile.Materials and Methods:Blood samples were collected from cows in different communal areas of Mafikeng. Convenience sampling was used to collect samples for the study. Blood samples were collected cows experiencing dystocia (n=50), retained placenta (n=13), downer cow syndrome (n=34), vaginal prolapse (n=16), and abortions (n=69), following cases reported at the Animal Health Hospital of the North-West University, Mafikeng Campus. Descriptive statistics, such as mean and standard deviations, were used to describe the distribution of hormone levels across reproductive conditions. p-value less than the significance level was set at 5% (p<0.05).Results:Data obtained revealed significantly higher estradiol in abortion (1122.99±71.99 pg/ml), downer cow syndrome (781.32±135.7 pg/ml), and dystocia (862.09±123.44 pg/ml). Oxytocin (OT) differed significantly in cows with dystocia (370.50±71.66 pg/ml) and abortion (574.73±60.65 pg/ml). Significantly low progesterone (Pg) was observed in abortion (2.45±1.509 ng/ml) and dystocia (8.59±0.402 ng/ml) while increased prostaglandin alpha was observed in cows with vaginal prolapse and abortion.Conclusion:The findings highlight an increase in serum estradiol and OT in aborting cows. Low Pg and estradiol in cows with vaginal prolapses and retained placenta were noted. An association was seen between downer cow syndrome and high concentrations of estradiol and Pg. Prostaglandin alpha may increase in cases of vaginal prolapse and abortion. Hormonal alterations were observed and may contribute to the incidences of different reproductive conditions.

Study on the Effects of Estradiol in Staphylococcus epidermidis Device-Related Capsule Formation.

Capsular contracture, mainly caused by Staphylococcus epidermidis (S. epidermidis) biofilm formation, is a complex problem for breast cancer patients who undergo surgical prosthetic breast reconstruction. Estradiol has been reported to be involved in the formation of bacterial biofilms. Thus, the underlying mechanism of estradiol in capsular contracture needs to be investigated. Biofilm-related gene expressions were measured by qRT-PCR after sterilizing the silicone with bacterial suspension and E2 treatment in vitro. Rat models were established with bilateral ovariectomy operations and estradiol subcutaneous injections. The effects of estradiol on capsular contracture were detected by monitoring serum estradiol levels, bacterial infection rate in organs, biofilm formation and capsular contracture in vivo; inflammatory factors in vivo were examined as well. Biofilm on the silicone implants was observed under a scanning electron microscope. Both positive regulatory genes and negative regulatory genes were increased by the high concentration of estradiol, suggesting that estradiol can promote the formation of biofilm by not only positive but also negative regulations. High estradiol levels increased bacterial infection rate in organs, biofilm formation and capsular contracture. Further, high estradiol caused a large number of inflammatory cells to infiltrate and caused serious inflammatory reactions that aggravate the immune imbalances of the host. High estradiol levels contribute to increasing capsular contracture caused by S. epidermidis biofilm formation. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

OSTEOARTHRITIS IN WOMEN: ARE THERE ANY DIFFERENCES? Review

Relevance. Female gender is known to be a major risk factor for osteoarthritis (OA). In addition, women with OA are characterized by some differences in the context of etiopathogenesis, clinical course and prognosis, and the question of clarifying the causes of these differences remains relevant.&#x0D; Objective: to review the literature data on the epidemiological, etiopathogenic and clinical features of OA in women, as well as the peculiarities of treatment and prognosis based on gender.&#x0D; Materials and methods. Analysis of scientific publications in the international electronic scientometric database PubMed using keywords "osteoarthritis", "women", "gender", "estrogens" over the period 1989-2019 years.&#x0D; Results. The incidence of OA is on average almost twice as high among women compared with men. Smoking, alcohol and heavy exercise are significant risk factors of OA for men, while the role of genetic factors is more significant for women. High concentrations of estradiol in women are associated with a lower degree of cartilage destruction, less significant productive synovitis and a lower rate of total arthroplasty. Women with knee OA are characterized by significantly higher pain intensity during walking and knee extension. The strength of quadriceps femoris muscle is significantly lower in women than in men, regardless of the severity of OA. Women with OA are characterized by a higher concentration of C-reactive protein, which is associated with a larger number of painful joints. Women are more likely than men to take non-steroidal anti-inflammatory drugs and use topical agents. The frequency of total arthroplasty among women is much higher, but early rehabilitation after it is relatively more favorable than in men.&#x0D; Conclusions. Sex hormones, genetic factors, lower extremity muscle strength, anatomical and kinematic features of the knee joints play an important role in the etiopathogenesis of OA in women. Women with OA are characterized by more intense and diffuse character of pain, more significant functional impairments compared to men.

Mitochondrial dysfunction induced by high estradiol concentrations in endometrial epithelial cells

Abstract Context A supraphysiological estradiol (E2) concentration after ovarian stimulation is known to result in lower embryo implantation rates in in vitro fertilization (IVF). Endometrial epithelial cells (EECs) apoptosis occurs after the stimulation with high E2 concentrations, and mitochondria play important roles in cell apoptosis. Objective To investigate the mitochondrial function in EECs after the stimulation with high E2 concentrations. Materials and Methods Human EECs were purified and cultured with different E2 concentrations (10-10, 10-9, 10-8, 10-7 M) in vitro, in which 10-7 M is supraphysiologically high. Eight-week-old female mouse endometrium was obtained 5.5 days after the injection of 1.25 IU or 20 IU equine chorionic gonadotropin (eCG), roughly during the embryo implantation window, to examine the in vivo effects of high E2 concentrations on mouse EECs. Results In vivo and in vitro experiments demonstrated decreased mitochondrial DNA contents and ATP formation after EECs were stimulated with supraphysiologically high E2 concentrations than those stimulated with a physiologic E2 concentration. Less prominent immunofluorescence mitochondrial staining, fewer mitochondria number under electron microscopy, lower JC-1 aggregate/monomer ratio, and greater reactive oxygen species (ROS) production were found after EECs were stimulated with supraphysiologically high E2 concentrations. The high E2-induced ROS production was reduced when EECs were pretreated with N-acetyl-cysteine (NAC) in vitro, but remained unchanged after the pretreatment with coenzyme Q10. Conclusion High E2 concentrations increase extra-mitochondrial ROS production in EECs and subsequently result in mitochondrial dysfunction.

Mitochondrial Dysfunction Induced by High Estradiol Concentrations in Endometrial Epithelial Cells

Abstract Context A supraphysiological estradiol (E2) concentration after ovarian stimulation is known to result in lower embryo implantation rates in in vitro fertilization. Endometrial epithelial cell (EEC) apoptosis occurs after the stimulation with high E2 concentrations, and mitochondria play important roles in cell apoptosis. Objective To investigate the mitochondrial function in EECs after the stimulation with high E2 concentrations. Materials and Methods Human EECs were purified and cultured with different E2 concentrations (10-10, 10–9, 10–8, 10–7 M) in vitro, in which 10–7 M is supraphysiologically high. Eight-week-old female mouse endometrium was obtained 5.5 days after the injection of 1.25 IU or 20 IU equine chorionic gonadotropin, roughly during the embryo implantation window, to examine the in vivo effects of high E2 concentrations on mouse EECs. Results In vivo and in vitro experiments demonstrated decreased mitochondrial DNA contents and ATP formation after EECs were stimulated with supraphysiologically high E2 concentrations than those stimulated with a physiologic E2 concentration. Less prominent immunofluorescence mitochondrial staining, fewer mitochondria numbers under electron microscopy, lower 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide aggregate/monomer ratio, and greater reactive oxygen species (ROS) production were found after EECs were stimulated with supraphysiologically high E2 concentrations. The high E2-induced ROS production was reduced when EECs were pretreated with N-acetyl-cysteine in vitro, but remained unchanged after the pretreatment with coenzyme Q10. Conclusion High E2 concentrations increase extramitochondrial ROS production in EECs and subsequently result in mitochondrial dysfunction.

Function of the hypothalamic-hypophysial axis during the post-partum period in ewes and cows

Summary. During pregnancy the hypothalamic–hypophysial axis is suppressed by the high concentrations of progesterone and oestradiol in the circulation. The high concentrations of these steroids appear to inhibit secretion of GnRH from the hypothalamus, resulting in inadequate stimulation of pituitary gonadotrophs to maintain synthesis of LH. This produces a depletion of LH in the anterior pituitary gland that must be restored after parturition before normal oestrous cycles can begin.