Estrogenic activities of two synthetic pyrethroids and their metabolites

Synthetic pyrethroids （SPs） are among the most common pesticides in current use, and so far, several SPs have been assessed for their potential estrogenicities by various methods. Previous studies have shown that the estrogenicities partly come from their metabolites. Although considerable information is available with respect to the metabolism and environmental degradation of SPs, little is known about the estrogenicities of the metabolites. In this study, permethrin （PM） and β-cypermethrin （CP）, as well as their metabolites （3-phenoxybenzoic alcohol （PBCOH）, 3-phenoxybenzaldehyde （PBCHO） and 3-phenoxybenzoic acid （PBCOOH） were evaluated for their estrogenic activities in the MCF-7 human breast carcinoma cell line. In the MCF-7 cell proliferation assay, PM and CP exhibited significant estrogenic activities at 10-7 mol/L, comparable to 17β-estradiol （E2） of 10-9 tool/L, with the relative proliferative effect ratios of 55.4% and 56.3%, respectively. The real-time quantitative polymerase chain reaction （qRT-PCR） results confirmed the estrogenicities of PM and CP with significant alteration of pS2 and ERα mRNA levels observed at 10-6 mol/L. For the three major metabolites, PBCOH and PBCOOH exhibited estrogenic activities in all assays, while no significant estrogenic responses was observed for PBCHO compared to the vehicle control. In particular, PBCOH had even slightly stronger estrogenic activity than its parent compounds, indicating that metabolism may be one of the reasons for the estrogenicities of the SPs. Given the widespread use of SPs, the toxicological effects of parent compounds and their metabolites should be taken into consideration in the risk assessment of SPs.

Estrogenic activity of hydroalcoholic extract of Clitoria ternatea Linn. leaves on rats

Objective:To assess the estrogenic activity of hydroalcoholic extract of Clitoria(C.)ternatea leaves in female Wistar rats.Methods:Hydroalcoholic extract of C.ternatea leaves prepared by using cold maceration method was tested for estrogenic activity.An acute toxicity study was conducted to estimate the safe dose using OECD 423 guidelines.For estrogenic activity,ovariectomized female rats were divided into four groups,with 6 rats in each group.The control and standard groups were administered with 1%carboxymethyl cellulose orally and estradiol valerate at 1μg/rat/day subcutaneously,respectively.The third group was administered with hydroalcoholic extract of C.ternatea at the dose 500 mg/kg body weight orally and the fourth group was administered with hydroalcoholic extract of C.ternatea at the dose 500 mg/kg body weight orally along with estradiol valerate at dose 1μg/rat/day subcutaneously.All treatments lasted for 7 consecutive days and estrogenic activity was assessed by observing vaginal cornfication.On day 8,all animals were sacrificed and uterine horns were dissected out.Utrine weight was measured and blood serum was further processed for the estimation of biochemical parameters like cholesterol,total proteins,alkaline phosphatase and estrogen by autoanylser.Histological studies of uterus were also carried out.Results:Acute toxicity studies indicated the hydroalcoholic extract of C.ternatea leave was found to be safe up to the dose level of 2000 mg/kg.Oral administration of C.ternatea extract at the dose 500 mg/kg body weight and and estradiol valerate(1μg/rat/day)caused morphological changes i.e.increase in uterine weight,vaginal opening and cornification of cells;biochemical changes i.e.increase in cholesterol,total protein,alkaline phosphatase and estrogen contents;histological changes i.e.increase in uterine diameter,thickness and height of endometrium.Simultaneous administration of C.ternatea extract with estradiol valerate showed a synergistic effect.Histological investigations further confirmed the strong estrogenic nature of C.ternatea extract.Conclusions:C.ternatea extract(500 mg/kg)showed a significant estrogenic activity which is also supported by biochemical and histological studies.So,on the basis of these findings,it can be concluded that C.ternatea can be used as an alternative to synthetic oral contraceptives.

Evaluation of the Estrogenic Activity of Pueraria (Kudzu) Flower Extract and Its Major Isoflavones Using ER-Binding and Uterotrophic Bioassays

Pueraria flower extract (PFE) is a hot water extract of the Kudzu flower (Pueraria thomsonii). Tea made from dried Kudzu flower is widely used inChina, and PFE is utilized as a nutritional supplement inJapan. PFE contains unique isoflavones such as 6-hydroxygenistein 6,7-di-O-glucoside (6HGDG), tectorigenin 7-O-xylosylglucoside (TGXG), and tectoridin. 6HGDG is known to be metabolized into 6-hydroxygenistein, and TGXG and tectoridin are known to be metabolized into tectorigenin in the digestive tract. Isoflavones typically mimic the effects β-estradiol has on estrogen receptors (ERs) and may influence the female genital system in the case of excessive intake. As a result, the upper limit of safe daily consumption of soy isoflavones has been enforced inJapan. In the present study, ER-binding assays were performed using the EnBio estrogen receptor/cofactor assay system to compare the estrogenic activity of 6-hydroxygenistein and tectorigenin to that of the soy isoflavone genistein. In addition, uterotrophic bioassays were performed to investigate the estrogenic effects of PFE in vivo. The ER-binding assays revealed that the ER-binding affinities of 6-hydroxygenistein and tectorigenin were approximately 0.01 - 0.04 that of genistein. Soy isoflavone products also induced an increase in uterine wet and blotted weight at doses of 500 mg/kg and 1000 mg/kg, whereas PFE did not cause adverse estrogenic effects, even at a dose of 1000 mg/kg. Based on these results, PFE does not appear to contain compounds with strong estrogenic activity or cause adverse estrogenic effects in vivo. Importantly, the results of this study confirm the safety of PFE as a food supplement.

New insights into estrogenic regulation of O^6-methylguanine DNA-methyltransferase (MGMT) in human breast cancer cells： Co-degradation of ER-α and MGMT proteins by fulvestrant or O^6-benzylguanine indicates fresh avenues for therapy

Endocrine therapy using estrogen receptor-u （ER-α） antagonists for attenuating horm2one-driven cell proliferation is a major treatment modality for breast cancers. To exploit any DNA repair deficiencies associated with endocrine therapy, we investigated the functional and physical interactions of ER-α with O^6-methylguanine DNA methyltransferase （MGMT）, a unique DNA repair protein that confers tumor resistance to various anticancer alkylating agents. The ER-α -positive breast cancer cell lines （MCF-7, T47D） and ER- negative cell lines （MDAMB- 468, MDAMB-231）, and established inhibitors of ER-α and MGMT, namely, ICI-182,780 （Faslodex） and O^6- benzylguanine, respectively, were used to study MGMT- ER interactions. The MGMT gene promoter was found to harbor one full and two half estrogen-responsive elements （EREs） and two antioxidant-responsive elements （AREs）. MGMT expression was upregulated by estrogen, downregulated by tamoxifen in Western blot and promoter-linked reporter assays. Similarly, both transient and stable transfections of Nrf-2 （nuclear factor-erythroid 2-related factor-2） increased the levels of MGMT protein and activity 3 to 4-fold reflecting novel regulatory nodes for this dragresistance determinant. Of the different ER-α antagonists tested, the pure anti-estrogen fulvestrant was most potent in inhibiting the MGMT activity in a dose, time and ER-α dependent manner, similar to O^6-benzylguanine. Interestingly, fulvestrant exposure led to a degradation of both ER-α and MGMT proteins and O^6-benzylguanine also induced a specific loss of ER-a and MGMT proteins in MCF-7 and T47D breast cancer cells with similar kinetics. Immunoprecipitation revealed a specific association of ER-a and MGMT proteins in breast cancer cells. Furthermore, silencing of MGMT gene expression triggered a decrease in the levels of both MGMT and ER-a proteins. The involvement of proteasome in the drug-induced degradation of both proteins was also demonstrated. Fulvestrant enhanced the cytotoxicity of MGMT-targeted alkylating agents, namely, temozolomide and BCNU by 3 to 4-fold in ER-α positive cells, but not in ER-negative cells. We conclude that MGMT and ER-α proteins exist as a complex and are co-targeted for ubiquitin-conjugation and subsequent proteasomal degradation. The findings offer a clear rationale for combining alkylating agents with endocrine therapy.

Bioassay of Estrogenic Activity of Effluent and Influent in a Farm Wastewater Treatment Plant Using an in vitro Recombinant Assay with Yeast Cells

Objective Environmental estrogens at an elevated concentration are known to produce adverse effects on human and animal life. However, the majority of researches have been focused on industrial discharges, while the impact of livestock wastes as a source of endocrine disrupters in aquatic environments has been rarely elucidated. In order to investigate the contribution of environmental estrogens from livestock, the estrogenic activity in water samples from a farm wastewater treatment plant was analyzed by a recombinant yeast screening method. Methods The extracts prepared from 15 selected water samples from the farm wastewater treatment plant, among which 6 samples were from pre-treatment section （influents） and 9 from post-treatment section （effluents）, were analyzed for estrogenic activity by cellar bioassay. Yeast cells transfected with the expression plasmid of human estrogen receptor and the Lac Z reporter plasmid encoding β-galactossidase, were used to measure the estrogen-like compounds in the farm wastewater treatment plant. Results The wastewater samples from influents showed a higher estrogenic potency than the effluent samples showing a low induction of β-galactossidase relative to solvent control condition. By comparison with a standard curve for 17β-estradiol （E2）, estrogenic potency in water samples from the influents was calculated as E2-equivalent and ranged from 0.1 to 150 pM E2-equivalent. The estrogenic potency in water samples from the effluents was significantly lower than that in the influents, and 7 water samples had less detectable limit in the total of 9 samples. Conclusion Yeast bioassay of estrogenic activity in most of the samples from the farm wastewater after disposal by traditional sewage treatment showed negative results.

Mutagenic and Estrogenic Effects of Organic Compounds in Water Treated by Different Processes: A Pilot Study

Objective In this study, a pilot-scale investigation was conducted to examine and compare the biotoxicity of the organic compounds in effluents from five treatment processes (P1-P5) where each process was combination of preoxidation (O3), coagulation, sedimentation, sand filtration, ozonation, granular activated carbon, biological activated carbon and chlorination (NaClO). Methods Organic compounds were extracted by XAD-2 resins and eluted with acetone and dichlormethane (DCM). The eluents were evaporated and redissolved with DMSO or DCM. The mutagenicity and estrogenicity of the extracts were assayed with the Ames test and yeast estrogen screen (YES assay), respectively. The organic compounds were detected by GC-MS. Results The results indicated that the mutation ratio (MR) of organic compounds in source water was higher than that for treated water. GC-MS showed that more than 48 organic compounds were identified in all samples and that treated water had significantly fewer types and concentrations of organic compounds than source water. Conclusion To different extents, all water treatment processes could reduce both the mutagenicity and estrogenicity, relative to source water. P2, P3, and P5 reduced mutagenicity more effectively, while P1 reduced estrogenicity, most effectively. Water treatment processes in this pilot plant had weak abilities to remove Di-n-butyl phthalate or 1, 2-Benzene dicarboxylic acid.

LAMP2 is involved in estrogenic deficiency induced spatial memory impairment through autophagy-AB pathway

LAMP2(lysosome associated membrane glycoprotein 2)is an important autophagy protein but its role in estrogenic regulation on spatial learning and memory remains unclear.In this study,we first infused aromatase(estrogen synthase)-specific RNA interference AAV into the hippocampus of mice,label-free quantitative proteomics analysis revealed that LAMP2 was the most significantly upregulated protein.This upregulation was further proved with RT-PCR,WB,IHC in ovariectomy(OVX)mice.Then,LAMP2-overexpressing(oLAMP2)and RNA interference(shLAMP2)virus vectors were injected into the hippocampus of OVX mice,respectively.

Assessment of source water contamination by estrogenic disrupting compounds in China

Detection of estrogenic disrupting compounds（EDCs） in drinking waters around China has led to rising concerns about health risks associated with these compounds.There is,however,a paucity of studies on the occurrence and identification of the main compounds responsible for this pollution in the source waters.To fill this void,we screened estrogenic activities of 23 source water samples from six main river systems in China,using a recombinant two-hybrid yeast assay.All sample extracts induced significant estrogenic activity,with E2 equivalents（EEQ） of raw water ranging from 0.08 to 2.40 ng/L.Additionally,16 samples were selected for chemical analysis by gas chromatography-mass spectrometry.The EDCs of most concern,including estrone（E1）,17β-estradiol（E2）,17α-ethinylestradiol（EE2）,estriol（E3）,diethylstilbestrol（DES）,estradiol valerate（EV）,4-t-octylphenol（4-t-OP）,4-nonylphenols（4-NP） and bisphenol A（BPA）,were determined at concentrations of up to 2.98,1.07,2.67,4.37,2.52,1.96,89.52,280.19 and 710.65 ng/L,respectively.Causality analysis,involving comparison of EEQ values from yeast assay and chemical analysis identified E2,EE2 and 4-NP as the main responsible compounds,accounting for the whole estrogenic activities（39.74% to 96.68%）.The proposed approach using both chemical analysis and yeast assay could be used for the identification and evaluation of EDCs in source waters of China.

Estrogenic activity of osthole and imperatorin in MCF-7 cells and their osteoblastic effects in Saos-2 cells

There is an increasing interest in phytoestrogens due to their potential medical usage in hormone replacement therapy(HRT). The present study was designed to investigate the in vitro effects of estrogen-like activities of two widespread coumarins, osthole and imperatorin, using the MCF-7 cell proliferation assay and their alkaline phosphatase(ALP) activities in osteoblasts Saos-2 cells. The two compounds were found to strongly stimulate the proliferation of MCF-7 cells. The estrogen receptor-regulated ERα, progesterone receptor(PR) and PS2 m RNA levels were increased by treatment with osthole and imperatorin. All these effects were significantly inhibited by the specific estrogen receptor antagonist ICI182, 780. Cell cycle analysis revealed that their proliferation stimulatory effect was associated with a marked increase in the number of MCF-7 cells in S phase, which was similar to that observed with estradiol. It was also observed that they significantly increased ALP activity, which was reversed by ICI182,780. These results suggested that osthole and imperatorin could stimulate osteoblastic activity by displaying estrogenic properties or through the ER pathway. In conclusion, osthole and imperatorin may represent new pharmacological tools for the treatment of osteoporosis.

Occurrence of estrogenic endocrine disrupting chemicals concern in sewage plant effluent

The purpose of this study was to give a worldwide overview of the concentrations of typical estrogenic endocrine disrupting chemicals （EDCs） in the effluent of sewage plants and then compare the concentra- tion distribution of the estrogenic EDCs in ten countries based on the survey data of the estrogenic EDCs research. The concentrations of three main categories （totally eight kinds） of estrogenic EDCs including steroidal estrogens （estrone （El）, estradiol （E2）, estriol （E3） and 17a- ethynylestradiol （EE2））, phenolic compounds （nonylphe- nol （NP） and bisphenol A （BPA）） and phthalate esters （dibutyl phthalate （DBP） and dibutyl phthalate （2- ethylhexyl） phthalate （DEHP）） in the effluents of sewage plants reported in major international journals over the past decade were collected. The statistics showed that the concentration distributions of eight kinds of EDCs were in the range of ng·L^-1 to μg·L^-1. The concentrations of steroidal estrogens mainly ranged within 50.00 ng. L-1, and the median concentrations of El, E2, E3 and EE2 were 11.00, 3.68, 4.90 and 1.00 ng·L^-1, respectively. Phenolic compounds and phthalate esters were found at pg. L-1 level （some individual values were at the high level of 40.00 μg·L^-1）. The median concentrations of BPA, NP, DBP and DEHP were 0.06, 0.55, 0.07 and 0.88 μg·L^-1, respectively. The concentrations of phenolic compounds and phthalate esters in the effluents were higher than that of steroids estrogens. The analysis of the concentration in various ten countries showed that steroids estrogens, phenolic compounds and phthalate esters in sewage plant effluents were detected with high concentration in Canada, Spain and China, respectively.

Effects of nanoscale quantum dots in male Chinese loaches (Misgurnus anguillicaudatus):Estrogenic interference action,toxicokinetics and oxidative stress

Quantum dots (QDs) have received more and more attention as a novel example of nanocrystals due to their unique fluorescent characteristics. Recently, the toxicity and the potential environmental effects of QDs have become a research hotspot. In this work, in vivo endocrine disrupting effect, toxicokinetics and oxidative stress of QDs were characterized following the intraperitoneal dosing in Chinese loaches. Vitellogenin (Vtg) levels induced by E2 decreased significantly when administrated with the mixture of QDs and E2, which was consistent with the observations of histopathology in testes. The release of free Cd2+ from QDs and the non-specific adsorption of E2 by QDs might be the joint factors contributing to the inhibition of Vtg expression induced by E2 in the male Chinese loaches. In the muscle, bone, intestines, blood and testis, CdSe QDs reached the maximal concentration (Cmax) in approximately 1-h postinjection and subsequently presented downtrend with the prolonged time. Whereas, there were even increasing tendencies of CdSe QDs' concentrations in the liver and kidney. It is educible that CdSe QDs can be persistent at least for 7 days, indicating the overall half-life of CdSe QDs in the fish body is very long. The measurement of hepatic superoxide dismutase (SOD) activity and reduced glutathione (GSH) content indicate that QDs have smaller effects on the antioxidative system of the organisms compared with free Cd2+ due to the effective prevention of the release of Cd by PEG coating of QDs. The comprehensive evaluation of QDs' toxicity in the present study provides an essential and general framework towards more focused research on the elucidation of the biological effects of QDs in vivo.

Oxidation of estrone by permanganate: Reaction kinetics and estrogenicity removal

Permanganate was used as an oxidant to control estrone in the present study. Kinetics was determined at pH 2.5-9.4 and temperature 15–40°C for the reaction of estrone with potassium permanganate. It was found that the reaction is second-order overall and first-order with respect to both estrone and permanganate. The second-order rate constant for the reaction at pH 5.8 and 25°C is 44.45 L mol-1 s-1. The reaction rate first decreased with the increase of pH in the range of 2.5-6.6 and then increased greatly with the increase of pH in the range of 6.6-9.4. In addition, the rate constant exponentially increased with the increase of reaction temperature. Removal of estrogenicity was also investigated during the degradation of estrone using yeast estrogen screen (YES). Results show that the estrogenicity increased in the initial 15 min of reaction and then decreased fast, with a removal rate of 73.8% within the 30 min of reaction. Results also demonstrate that the reaction rate between estrone and permanganate is faster in natural water background than in the ultra-pure water system. Permanganate oxidation is therefore a feasible option for removal of estrone in drinking water treatment processes. However, the contact time must be enough in order to remove estrone without causing the increase of estrogenicity.

Estrogenic effects of water from the Yangtze River (Nanjing section) on goldfish (Carassius auratus) after an early life stage exposure

Effects of river water from the Yangtze River （Nanjing section） on fish development, vitellogenin （VTG） induction, gonado-somatic index （GSI） and sex ratio were investigated by exposing goldfish （Carassius auratus） in the early life stage （from fertilization to 28 days post-hatch） to water samples （25%, 50% and 100%） collected from three representative sections. The results showed that there was no significant effect on hatching success for any of the exposure groups, but survival was significantly reduced when compared with the control （P 0.05）. Body lengths, weights of all treated fish did not differ significantly from those of the control. Condition factors （CF） of larval fish exposed to 50% and 100% river water from the Jiangxinzhou section and 100% river water from the Daqiao section were significantly lower than that of the control （P 0.05）. VTG inductions were significant in larval fish exposed to all the dilution series of river water. No significant difference in CF value was observed in any exposure group after 150 days of depuration. VTG was fully eliminated after 75 days of depuration. For both female and male, GSI did not significantly differ between exposure groups and the control after 150 days of convalescence. The highest female：male ratios were observed in response to the treatment with 50% or 100% river water from the Jiangxinzhou section and 100% river water from the Daqiao section （53：47, 56：44 and 54：46, respectively）, but no significant difference in sex ratio was observed in any treated group when compared to the control. The results showed that early life stage exposure of river water from the Yangtze River （Nanjing section） had adverse effects on goldfish development and reproductive health, and the effects on CF and VTG were reversible after depuration in clean water.

Photodegradation of 17α-ethynylestradiol in dissolved humic substances solution：Kinetics,mechanism and estrogenicity variation

17α-Ethynylestradiol（EE2） in natural waters may cause adverse effects on organisms due to its high estrogenic potency. Laboratory studies were performed to study the effects of a local humic acid（LHA）, fulvic acid（LFA） and Aldrich humic acid（AHA） on the photochemical behavior and estrogenic potency of EE2. Here photolytic experiments demonstrated that pure aqueous EE2 could undergo direct and self-sensitized photodegradation at a global rate of 0.0068 hr^-1.Photodegradation rate of EE2 in 5.0 mg/L dissolved humic substances（DHS） was determined to be 0.0274, 0.0296 and 0.0254 hr^-1 for LHA, LFA and AHA, respectively. Reactive oxygen species（ROS） and triplet dissolved humic substances（^3DHS＊） scavenging experiments indicated that the promotion effect of DHS on EE2 photodegradation was mainly aroused by the reactions of HOU（35%–50%）,~1O2（〈10%） andDHS＊（22%–34%）. However, the photodegradation of EE2 could also be inhibited when DHS exceeded the threshold of 10 mg/L. Three hydroxylation products of EE2 were identified using GC–MS and their formation pathways were also proposed. In vitro estrogenicity tests showed that EE2 was transformed into chemicals without estrogenic potency. These findings could extend our knowledge on the photochemical behaviors of steroid estrogens in sunlit natural waters.

Clinicopathological Features and Long-Term Prognostic Role of Human Epidermal Growth Factor Receptor-2 Low Expression in Chinese Patients with Early Breast Cancer:A Single-Institution Study

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC.Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups.Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszelχ^(2)test,P<0.001,Pearson’s R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%.Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Major royal-jelly proteins intake modulates immune functions and gut microbiota in mice

In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to mitogens.The splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand IL-17A.The release of IL-4 was unaffected by MRJPs.Additionally,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory cytokines.The production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control group.Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice.Additionally,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and Shigella.Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.

Engineering of ovarian tissue for ovarian dysfunctions:A review

This review explores tissue engineering as a potential solution for reproductive health issues in women caused by genetic or acquired diseases,such as premature ovarian failure or oophorectomy.The loss of ovarian function can lead to infertility,osteoporosis,and cardiovascular disease.Hormone replacement therapy is a common treatment,but it has limitations and risks.The review focuses on two main approaches in tissue engineering:scaffold-based(3D printing,electrospinning,decellularization)and scaffold-free(stem cell transplantation,organoid cultivation).Both approaches show promise in preclinical studies for creating functional ovarian tissue.Challenges include vascularization,innervation,long-term function,and safety.Despite these challenges,tissue engineering offers a potential avenue for restoring fertility and hormone balance in women with ovarian dysfunction.

Does local vaginal estrogen after tension-free transobturator vaginal tape reduce overactive bladder symptoms in postmenopausal women? A prospective randomized, controlled study

Objective:We aimed to evaluate the efficacy of topical estrogen after transvaginal tension-free vaginal tape-obturator(TVT-O)in the treatment of de novo overactive bladder symptoms that appear after surgery.Methods:This is a prospective randomized controlled study performed in the Urology and Gynecology Departments,Kasr Al Ainy Hospital,Cairo University,Cairo,Egypt.Two hundred and ten postmenopausal females presenting during the period between January 2017 and November 2020 with stress urinary incontinence were included in the study.Patients were divided into two groups,105 patients in Group A(treatment group)and 105 patients in Group B(control group).Patients in Group A underwent transvaginal TVT-O followed by local vaginal estrogen treatment for 6 months,while patients in Group B underwent transvaginal TVT-O only.The study included any postmenopausal female with urodynamic stress urinary incontinence.All patients had to fulfill a 3-day bladder diary,overactive bladder symptoms score,urine analysis,urodynamic study,and post-voiding residual urine measurement by abdominal ultrasound preoperatively and at 3-month and 6-month follow-ups.Results:At 6-month follow-up,daytime frequency was reduced to 8%in Group A(increased to 21%in Group B)with a statistically significant difference between both groups(p=0.009).At 6-month follow-up,nocturia was 8%in Group A(11%in Group B)with no statistically significant difference between both groups(p=0.469).There was a statistically significant difference between both groups as regards to urinary urgency at 6-month follow-up(p=0.024).There was a statistically significant difference in postoperative wound healing events as regards to cure,hyperemia,gapping,and wound infection 1 week after intervention between both groups(p=0.008).No local or systemic side-effects were reported from local estrogen use.Conclusion:Local vaginal estrogen treatment given to postmenopausal patients after midurethral sling procedures can reduce the symptoms of daytime frequency and urinary urgency.Long-term follow-up is needed.

Gut microbiota and female health

The gut microbiota is recognized as an endocrine organ with the capacity to influence distant organs and associated biological pathways.Recent advan-cements underscore the critical role of gut microbial homeostasis in female health;with dysbiosis potentially leading to diseases among women such as polycystic ovarian syndrome,endometriosis,breast cancer,cervical cancer,and ovarian cancer etc.Despite this,there has been limited discussion on the underlying mechanisms.This editorial explores the three potential mechanisms through which gut microbiota dysbiosis may impact the development of diseases among women,namely,the immune system,the gut microbiota-estrogen axis,and the metabolite pathway.We focused on approaches for treating diseases in women by addressing gut microbiota imbalances through probiotics,prebiotics supple-mentation,and fecal microbiota transplantation(FMT).Future studies should focus on determining the molecular mechanisms underlying associations between dysbiosis of gut microbiota and female diseases to realize precision medicine,with FMT emerging as a promising intervention.

Estrogen restores disordered lipid metabolism in visceral fat of prediabetic mice

BACKGROUND Visceral obesity is increasingly prevalent among adolescents and young adults and is commonly recognized as a risk factor for type 2 diabetes.Estrogen[17β-estradiol(E2)]is known to offer protection against obesity via diverse me-chanisms,while its specific effects on visceral adipose tissue(VAT)remain to be fully elucidated.AIM To investigate the impact of E2 on the gene expression profile within VAT of a mouse model of prediabetes.METHODS Metabolic parameters were collected,encompassing body weight,weights of visceral and subcutaneous adipose tissues(VAT and SAT),random blood glucose levels,glucose tolerance,insulin tolerance,and overall body composition.The gene expression profiles of VAT were quantified utilizing the Whole Mouse Genome Oligo Microarray and subsequently analyzed through Agilent Feature Extraction software.Functional and pathway analyses were conducted employing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses,respectively.RESULTS Feeding a high-fat diet(HFD)moderately increased the weights of both VAT and SAT,but this increase was mitigated by the protective effect of endogenous E2.Conversely,ovariectomy(OVX)led to a significant increase in VAT weight and the VAT/SAT weight ratio,and this increase was also reversed with E2 treatment.Notably,OVX diminished the expression of genes involved in lipid metabolism compared to HFD feeding alone,signaling a widespread reduction in lipid metabolic activity,which was completely counteracted by E2 adminis-tration.This study provides a comprehensive insight into E2's local and direct protective effects against visceral adiposity in VAT at the gene level.CONCLUSION In conclusion,the present study demonstrated that the HFD-induced over-nutritional challenge disrupted the gene expression profile of visceral fat,leading to a universally decreased lipid metabolic status in E2 deficient mice.E2 treatment effectively reversed this condition,shedding light on the mechanistic role and therapeutic potential of E2 in combating visceral obesity.