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Alexander Tacey Institute for Health and Sport (IHES), Victoria University, Melbourne, Victoria, Australia
Department of Medicine-Western Health, Australian Institute for Musculoskeletal Science (AIMSS), Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia

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Lewan Parker Institute for Health and Sport (IHES), Victoria University, Melbourne, Victoria, Australia
Institute for Physical Activity and Nutrition, Deakin University, Geelong, Victoria, Australia

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Bu B Yeap Medical School, University of Western Australia, and Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Western Australia, Australia

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John Joseph PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia

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Ee M Lim PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia

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Andrew Garnham Institute for Health and Sport (IHES), Victoria University, Melbourne, Victoria, Australia

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David L Hare University of Melbourne and the Department of Cardiology, Austin Health, Melbourne, Victoria, Australia

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Tara Brennan-Speranza Department of Physiology and Bosch Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia

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Itamar Levinger Institute for Health and Sport (IHES), Victoria University, Melbourne, Victoria, Australia
Department of Medicine-Western Health, Australian Institute for Musculoskeletal Science (AIMSS), Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia

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The aim of this study was to investigate the effect of a single dose of prednisolone on (A) high-intensity interval cycling performance and (B) post-exercise metabolic, hormonal and haematological responses. Nine young men participated in this double-blind, randomised, cross-over study. The participants completed exercise sessions (4 × 4 min cycling bouts at 90–95% of peak heart rate), 12 h after ingesting prednisolone (20 mg) or placebo. Work load was adjusted to maintain the same relative heart rate between the sessions. Exercise performance was measured as total work performed. Blood samples were taken at rest, immediately post exercise and up to 3 h post exercise. Prednisolone ingestion decreased total work performed by 5% (P < 0.05). Baseline blood glucose was elevated following prednisolone compared to placebo (P < 0.001). Three hours post exercise, blood glucose in the prednisolone trial was reduced to a level equivalent to the baseline concentration in the placebo trial (P > 0.05). Prednisolone suppressed the increase in blood lactate immediately post exercise (P < 0.05). Total white blood cell count was elevated at all time-points with prednisolone (P < 0.01). Androgens and sex hormone-binding globulin were elevated immediately after exercise, irrespective of prednisolone or placebo. In contrast, prednisolone significantly reduced the ratio of testosterone/luteinizing hormone (P < 0.01). Acute prednisolone treatment impairs high-intensity interval cycling performance and alters metabolic and haematological parameters in healthy young men. Exercise may be an effective tool to minimise the effect of prednisolone on blood glucose levels.

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Katarzyna Wyskida Health Promotion and Obesity Management Unit, Department of Pathophysiology, Medical Faculty of Silesia in Katowice, Medical University of Silesia, Katowice, Poland

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Grzegorz Franik Department of Gynecological Endocrinology, Medical Faculty of Silesia in Katowice, Medical University of Silesia, Katowice, Poland

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Tomasz Wikarek Department of Gynecology, Medical Faculty of Silesia in Katowice, Medical University of Silesia, Katowice, Poland

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Aleksander Owczarek Department of Statistics, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland

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Alham Delroba Health Promotion and Obesity Management Unit, Department of Pathophysiology, Medical Faculty of Silesia in Katowice, Medical University of Silesia, Katowice, Poland

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Jerzy Chudek Pathophysiology Unit, Department of Pathophysiology, Medical Faculty of Silesia in Katowice, Medical University of Silesia, Katowice, Poland

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Jerzy Sikora Department of Perinatology and Gynecology, Medical University of Silesia, Katowice, Poland

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Magdalena Olszanecka-Glinianowicz Health Promotion and Obesity Management Unit, Department of Pathophysiology, Medical Faculty of Silesia in Katowice, Medical University of Silesia, Katowice, Poland

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Context

The aim of this study was to assess the plasma leptin, adiponectin, resistin, visfatin/NAMPT, omentin-1, vaspin, apelin, TNF-α, IL-6 and RBP4 levels in relation to hormonal changes during the menstrual cycle in young, healthy, normal-weight women.

Methods

The study involved 52 young, healthy, normal-weight women. Anthropometric parameters, body composition and levels of plasma leptin, adiponectin, resistin, visfatin/NAMPT, omentin-1, vaspin, apelin, TNF-α, IL-6 and RBP4 in addition to serum FSH, LH, estradiol, progesterone, 17-OH progesterone, androgens, SHBG and insulin concentrations were measured during a morning in fasting state three times: between days 2–4, days 12–14 and days 24–26 of the menstrual cycle.

Results

Plasma adiponectin, omentin-1, resistin and visfatin/NAMPT, apelin, TNF-α, IL-6 and RBP4 concentrations were stable during the menstrual cycle, while leptin and vaspin levels were significantly higher in both the midcycle and the luteal phases than those in the follicular phase. Multivariate regression analyses revealed that changes in leptin and vaspin levels between the follicular and the luteal phase are strongly related to changes in total testosterone levels.

Conclusions

Our results revealed stable levels of adipokines during the phases of the physiological menstrual cycle, except for leptin and vaspin, which showed increased levels in both the midcycle and the luteal phases. This effect was significantly associated with changes in the secretion of testosterone, 17-OH progesterone and insulin in the luteal phase.

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Jennifer K Y Ko Department of Women’s Health, University College London Hospital, London, UK

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Thomas F J King Department of Women’s Health, University College London Hospital, London, UK

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Louise Williams Department of Women’s Health, University College London Hospital, London, UK

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Sarah M Creighton Department of Women’s Health, University College London Hospital, London, UK

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Gerard S Conway Department of Women’s Health, University College London Hospital, London, UK

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Objective

To review the treatment choices of women with complete androgen insensitivity syndrome (CAIS) at a single tertiary centre.

Design

Retrospective review.

Patients

Women with CAIS identified from our database.

Results

The study group comprised 141 women with CAIS. Eleven percent (16/141) of women had gonads in situ, 3 of whom were under workup for gonadectomy. The age of gonadectomy in the remainder 125 women was 17 (0.1–53) years. The most common form of HRT was oral oestrogen or transdermal oestrogen in 80% (113/141). 13/141 (9%) women used vaginal oestrogens alone or together with other forms of HRT. Testosterone preparations had been used by 17% (24/141) of women and were currently used in 10% (14/141). Of those who had used testosterone, 42% (10/24) had chosen not to continue after a therapeutic trial.

Conclusions

In a clinic offering individualised multidisciplinary care for women with CAIS, we found that the majority of women chose oestrogen-based treatment while a significant minority used testosterone.

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T S Nilsen Department of Physical Performance, Norwegian School of Sports Sciences, Oslo, Norway

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L Thorsen Department of Oncology, Oslo University Hospital, Oslo, Norway

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C Kirkegaard Department of Physical Performance, Norwegian School of Sports Sciences, Oslo, Norway

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I Ugelstad Department of Physical Performance, Norwegian School of Sports Sciences, Oslo, Norway

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S D Fosså Department of Oncology, Oslo University Hospital, Oslo, Norway

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T Raastad Department of Physical Performance, Norwegian School of Sports Sciences, Oslo, Norway

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Background

Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with several side effects, including loss of muscle mass. Muscle atrophy is associated with reduced mitochondrial function and increased muscle cellular stress that may be counteracted by strength training. Thus, the aim of this study was to investigate the effect of strength training on mitochondrial proteins and indicators of muscle cellular stress in PCa patients on ADT.

Methods

Men diagnosed with locally advanced PCa receiving ADT were randomised to a strength training group (STG) (n=16) or a control group (CG) (n=15) for 16 weeks. Muscle biopsies were collected pre- and post-intervention from the vastus lateralis muscle, and analysed for mitochondrial proteins (citrate synthase, cytochrome c oxidase subunit IV (COXIV), HSP60) and indicators of muscle cellular stress (heat shock protein (HSP) 70, alpha B-crystallin, HSP27, free ubiquitin, and total ubiquitinated proteins) using Western blot and ELISA.

Results

No significant intervention effects were observed in any of the mitochondrial proteins or indicators of muscle cellular stress. However, within-group analysis revealed that the level of HSP70 was reduced in the STG and a tendency towards a reduction in citrate synthase levels was observed in the CG. Levels of total ubiquitinated proteins were unchanged in both groups.

Conclusion

Although reduced HSP70 levels indicated reduced muscle cellular stress in the STG, the lack of an intervention effect precluded any clear conclusions.

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Angela Köninger
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Philippos Edimiris
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Laura Koch
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Antje Enekwe
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Claudia Lamina Department of Gynecology and Obstetrics, Division of Genetic Epidemiology, Vitateq Biotechnology GmbH, University of Duisburg-Essen, D-45122 Essen, Germany

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Sabine Kasimir-Bauer
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Rainer Kimmig
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Hans Dieplinger Department of Gynecology and Obstetrics, Division of Genetic Epidemiology, Vitateq Biotechnology GmbH, University of Duisburg-Essen, D-45122 Essen, Germany
Department of Gynecology and Obstetrics, Division of Genetic Epidemiology, Vitateq Biotechnology GmbH, University of Duisburg-Essen, D-45122 Essen, Germany

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Oxidative stress seems to be present in patients with polycystic ovary syndrome (PCOS). The aim of this study was to evaluate the correlation between characteristics of PCOS and serum concentrations of afamin, a novel binding protein for the antioxidant vitamin E. A total of 85 patients with PCOS and 76 control subjects were investigated in a pilot cross-sectional study design between 2009 and 2013 in the University Hospital of Essen, Germany. Patients with PCOS were diagnosed according to the Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group. Afamin and diagnostic parameters of PCOS were determined at early follicular phase. Afamin concentrations were significantly higher in patients with PCOS than in controls (odds ratio (OR) for a 10 mg/ml increase in afamin=1.3, 95% CI=1.08–1.58). This difference vanished in a model adjusting for age, BMI, free testosterone index (FTI), and sex hormone-binding globulin (SHBG) (OR=1.05, 95% CI=0.80–1.38). In patients with PCOS, afamin correlated significantly with homeostatic model assessment-insulin resistance (HOMA-IR), fasting glucose, BMI, FTI, and SHBG (P<0.001), but in a multivariate linear model, only HOMA-IR remained significantly associated with afamin (P=0.001). No correlation was observed between afamin and androgens, LH, FSH, LH/FSH ratio, antral follicle count, ovarian volume, or anti-Müllerian hormone. In conclusion, elevated afamin values may indicate a state of oxidative stress and inflammation, strongly associated with IR and offering an indicator of impaired glucose tolerance in patients with PCOS irrespective of obesity.

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Neil R Chappell Reproductive Endocrinology and Infertility Division, Department of Obstetrics and Gynecology, Baylor College of Medicine and Family Fertility Center, Texas Children’s Hospital, Houston, Texas, USA

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Beth Zhou Reproductive Endocrinology and Infertility Division, Department of Obstetrics and Gynecology, Baylor College of Medicine and Family Fertility Center, Texas Children’s Hospital, Houston, Texas, USA

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Amy K Schutt Reproductive Endocrinology and Infertility Division, Department of Obstetrics and Gynecology, Baylor College of Medicine and Family Fertility Center, Texas Children’s Hospital, Houston, Texas, USA

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William E Gibbons Reproductive Endocrinology and Infertility Division, Department of Obstetrics and Gynecology, Baylor College of Medicine and Family Fertility Center, Texas Children’s Hospital, Houston, Texas, USA

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Chellakkan S Blesson Reproductive Endocrinology and Infertility Division, Department of Obstetrics and Gynecology, Baylor College of Medicine and Family Fertility Center, Texas Children’s Hospital, Houston, Texas, USA

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Polycystic ovary syndrome (PCOS) is the most common ovulatory defect in women. Although most PCOS patients are obese, a subset of PCOS women are lean but show similar risks for adverse fertility outcomes. A lean PCOS mouse model was created using prenatal androgen administration. This developmentally programmed mouse model was used for this study. Our objective was to investigate if mitochondrial structure and functions were compromised in oocytes obtained from lean PCOS mouse. The lean PCOS mouse model was validated by performing glucose tolerance test, HbA1c levels, body weight and estrous cycle analyses. Oocytes were isolated and were used to investigate inner mitochondrial membrane potential, oxidative stress, lipid peroxidation, ATP production, mtDNA copy number, transcript abundance and electron microscopy. Our results demonstrate that lean PCOS mice have similar weight to that of the controls but exhibit glucose intolerance and hyperinsulinemia along with dysregulated estrus cycle. Analysis of their oocytes show impaired inner mitochondrial membrane function, elevated reactive oxygen species (ROS) and increased RNA transcript abundance. Electron microscopy of the oocytes showed impaired mitochondrial ultrastructure. In conclusion, the lean PCOS mouse model shows a decreased oocyte quality related to impaired mitochondrial ultrastructure and function.

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Zofia Kolesinska Department of Pediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, Poznan, Poland

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James Acierno Jr Endocrinology, Diabetology & Metabolism Service, Lausanne University Hospital, Lausanne, Switzerland

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S Faisal Ahmed Developmental Endocrinology Research Group, School of Medicine, Dentistry & Nursing, University of Glasgow, Glasgow, UK

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Cheng Xu Endocrinology, Diabetology & Metabolism Service, Lausanne University Hospital, Lausanne, Switzerland

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Karina Kapczuk Division of Gynecology, Department of Perinatology and Gynecology, Poznan University of Medical Sciences, Poznan, Poland

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Anna Skorczyk-Werner Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland

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Hanna Mikos Department of Pediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, Poznan, Poland

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Aleksandra Rojek Department of Pediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, Poznan, Poland

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Andreas Massouras Saphetor, SA, Lausanne, Switzerland

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Maciej R Krawczynski Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland

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Nelly Pitteloud Endocrinology, Diabetology & Metabolism Service, Lausanne University Hospital, Lausanne, Switzerland

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Marek Niedziela Department of Pediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, Poznan, Poland

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46,XY differences and/or disorders of sex development (DSD) are clinically and genetically heterogeneous conditions. Although complete androgen insensitivity syndrome has a strong genotype–phenotype correlation, the other types of 46,XY DSD are less well defined, and thus, the precise diagnosis is challenging. This study focused on comparing the relationship between clinical assessment and genetic findings in a cohort of well-phenotyped patients with 46,XY DSD. The study was an analysis of clinical investigations followed by genetic testing performed on 35 patients presenting to a single center. The clinical assessment included external masculinization score (EMS), endocrine profiling and radiological evaluation. Array-comparative genomic hybridization (array-CGH) and sequencing of DSD-related genes were performed. Using an integrated approach, reaching the definitive diagnosis was possible in 12 children. The correlation between clinical and genetic findings was higher in patients with a more severe phenotype (median EMS 2.5 vs 6; P = 0.04). However, in 13 children, at least one variant of uncertain significance was identified, and most times this variant did not correspond to the original clinical diagnosis. In three patients, the genetic studies guided further clinical assessment which resulted in a reclassification of initial clinical diagnosis. Furthermore, we identified eight patients harboring variants in more than one DSD genes, which was not seen in controls (2.5%; P = 0.0003). In summary, taking into account potential challenges in reaching the definitive diagnosis in 46,XY DSD, only integrated approach seems to be the best routine practice.

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María J Gómora Departamento de Embriología, Facultad de Medicina, Universidad Nacional Autónoma de México, CdMx, Mexico

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Flavia Morales-Vásquez Departamento de Oncología Médica, Instituto Nacional de Cancerología, Secretaría de Salud de México, CdMx, Mexico

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Enrique Pedernera Departamento de Embriología, Facultad de Medicina, Universidad Nacional Autónoma de México, CdMx, Mexico

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Delia Perez-Montiel Departamento de Patología, Instituto Nacional de Cancerología, Secretaría de Salud de México, CdMx, Mexico

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Horacio López-Basave Departamento de Cirugía Oncológica, Instituto Nacional de Cancerología, Secretaría de Salud de México, CdMx, Mexico

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Antonio R Villa División de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México, CdMx, Mexico

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Azucena Hernández-Martínez Hospital Militar de Especialidades de la Mujer y Neonatología, Secretaría de la Defensa Nacional, CdMx, Mexico

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Esteban Mena Unidad de Apoyo Académico, Secretaría General, Facultad de Medicina, Universidad Nacional Autónoma de México, CdMx, Mexico

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Carmen Mendez Departamento de Embriología, Facultad de Medicina, Universidad Nacional Autónoma de México, CdMx, Mexico

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The significance of the presence of androgen receptor (AR), estrogen receptor alpha (ER) and progesterone receptor (PR) in ovarian cancer patient survival has been a matter of numerous studies. This study was aimed to describe the expression profile of the three sexual steroid receptors in high-grade serous, endometrioid, mucinous and low-grade serous ovarian carcinoma and its association to the proliferation index in patients with primary ovarian carcinoma diagnosis, before any treatment. Eighty-one samples were obtained from the National Institute of Cancerology in Mexico City and were evaluated for the presence of AR, ER, PR and Ki67 by immunohistochemistry. The four subtypes of ovarian carcinoma displays a specific profile of the eight possible combinations of the steroid receptors with significant differences within the profile and the histological subtypes. High-grade serous carcinoma was characterized by a high frequency of both, triple-negative and AR+ ER− PR+ profiles. Endometrioid carcinoma presented a higher frequency of triple-positive profile. The presence of only AR+ profile was not observed in the endometrioid tumors. The relationship of the receptor profile with the proliferation index in the tumor epithelium shows that the expression of only ER is associated to a reduced proliferation index in endometrioid carcinoma. Steroid hormone receptor expression and co-expression could help characterize ovarian carcinoma.

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M Axelstad Technical University of Denmark, National Food Institute, Kongens Lyngby, Denmark

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U Hass Technical University of Denmark, National Food Institute, Kongens Lyngby, Denmark

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M Scholze Brunel University, Uxbridge, UK

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S Christiansen Technical University of Denmark, National Food Institute, Kongens Lyngby, Denmark

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A Kortenkamp Brunel University, Uxbridge, UK

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J Boberg Technical University of Denmark, National Food Institute, Kongens Lyngby, Denmark

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Human semen quality is declining in many parts of the world, but the causes are ill defined. In rodents, impaired sperm production can be seen with early life exposure to certain endocrine-disrupting chemicals, but the effects of combined exposures are not properly investigated. In this study, we examined the effects of early exposure to the painkiller paracetamol and mixtures of human relevant endocrine-disrupting chemicals in rats. One mixture contained four estrogenic compounds; another contained eight anti-androgenic environmental chemicals and a third mixture contained estrogens, anti-androgens and paracetamol. All exposures were administered by oral gavage to time-mated Wistar dams rats (n = 16–20) throughout gestation and lactation. In the postnatal period, testicular histology was affected by the total mixture, and at the end of weaning, male testis weights were significantly increased by paracetamol and the high doses of the total and the anti-androgenic mixture, compared to controls. In all dose groups, epididymal sperm counts were reduced several months after end of exposure, i.e. at 10 months of age. Interestingly, the same pattern of effects was seen for paracetamol as for mixtures with diverse modes of action. Reduced sperm count was seen at a dose level reflecting human therapeutic exposure to paracetamol. Environmental chemical mixtures affected sperm count at the lowest mixture dose indicating an insufficient margin of safety for the most exposed humans. This causes concern for exposure of pregnant women to paracetamol as well as environmental endocrine disrupters.

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Hong Tang Departments of Gynaecology and Obstetrics Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China

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Xiaomei Jiang Departments of Gynaecology and Obstetrics Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China

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Yu Hua Departments of Gynaecology and Obstetrics Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China

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Heyue Li Departments of Gynaecology and Obstetrics Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China

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Chunlan Zhu Departments of Gynaecology and Obstetrics Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China

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Xiaobai Hao Departments of Gynaecology and Obstetrics Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China

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Minhui Yi Departments of Gynaecology and Obstetrics Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China

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Linxia Li Departments of Gynaecology and Obstetrics Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China

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Background

Polycystic ovary syndrome (PCOS) is an androgen disorder and ovarian dysfunction disease in women of reproductive age. The cell death of granulosa cells (GCs) plays an important role in the development of PCOS. However, the mechanism of GC death is still unclear.

Methods

In the current study, NEDD4L was found to be elevated in PCOS GEO (Gene Expression Omnibus) databases and mouse models. The cell viability was analyzed by CCK-8 and FDA staining. The expression of ferroptosis markers was assessed by ELISA and immunofluorescence. The direct interaction of GPX4 and NEDD4L was verified by co-immunoprecipitation assay.

Result

Functionally, results from CCK-8 and FDA staining demonstrated that NEDD4L inhibited the cell viability of KGN cells and NEDD4L increased the levels of iron, malonyldialdehyde, and reactive oxygen species and decreased glutathione levels. Moreover, the cell death of KGN induced by NEDD4L was blocked by ferroptosis inhibitor, suggesting that NEDD4L regulates KGN cell ferroptosis. Mechanistically, NEDD4L directly interacts with GPX4 and promotes GPX4 ubiquitination and degradation.

Conclusion

Taken together, our study indicated that NEDD4L facilitates GC ferroptosis by promoting GPX4 ubiquitination and degradation and contributes to the development of PCOS.

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