Effects of clinical and metabolic variables and hormones on the expression of immune protein biomarkers in the endometrium of women with polycystic ovary syndrome and normal-cycling controls.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are at an elevated risk of endometrial cancer, which may be associated with the continuous proliferative state caused by the interaction between hormones and metabolic factors. OBJECTIVE: To investigate the impact of hormones and metabolic factors in the proliferation and death of endometrium during the proliferative phase. METHODS: Cross-sectional study with 11 women with PCOS and eight normal-cycling non-PCOS controls at the Federal University of the State of Rio de Janeiro from February 2011 to June 2019. Clinical, biochemical, and hormonal data were collected to analyze their influence on the expression of biomarkers related to the endometrial tissue breakdown. Hysteroscopy and endometrial biopsies were conducted, and the endometrial samples underwent immunohistochemistry for markers of apoptosis B-cell lymphoma 2 (BCL2), cleaved caspase-3 (CASP3), fas cell surface death receptor (FAS), FAS ligand (FASLG), BCL2 associated X (BAX), marker of proliferation Ki-67 (MKI67), and cell death using terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL). RESULTS: CASP3 and TUNEL expressions were lower in both stroma and endometrium gland of PCOS women than in controls. MKI67 and homeostasis indexes (BCL2/BAX; FASLG/FAS) in the endometrium of the PCOS group were significantly higher. Body mass index (BMI) values were positively correlated with the expression of MKI67 and MKI67/TUNEL ratio in the endometrial stroma compartment. Fasting insulin levels were positively correlated with the expression of BCL2, and DHEA-S levels were negatively correlated with the expression of CASP3 of women with PCOS. CONCLUSION: BMI, insulin, and DHEA-S influence the endometrial homeostasis breakdown in PCOS in the endometrium stroma.

Analysis of hyaluronic acid in the endometrium of women with polycystic ovary syndrome.

Endometrium extracellular matrix provides a wide range of signals at different cellular levels, like cell death and proliferation, which can be important for regulating menses and reducing the proliferative processes. The objective of this study is to evaluate hyaluronic acid concentration, the enzymes of hyaluronic acid synthases in the endometrium of patients with polycystic ovary syndrome (PCOS) and eumenorrheic women. A total of 60 endometrial samples from 30 patients with PCOS and 30 women with regular menstrual cycles in the proliferative phase, attended at Gynecology Division of Clinical Hospital of the FMUSP (HC-USP). Profile determination and the concentration of hyaluronic acid was performed by the biochemical method of the fluorimetric assay (ELISA-like). Its location in the endometrial tissue as well as the dosage of enzymes synthases (HAS1, HAS2 and HAS3) was done by immunohistochemistry and western blotting. Statistical analyses were performed with one-way ANOVA, followed by the Bonferroni test. Regarding hyaluronic acid synthases, there was a higher HAS1 and HAS2 reactivity and lower HAS3 reactivity in the PCOS endometrium compared to women with regular menstrual cycles in the proliferative phase. We suggest that PCOS patients have different composition of hyaluronic acid in relation to a regular cycle in the proliferative phase.

Accuracy of Ultrasonography in the Evaluation of Tubal Sterilization Microinsert Positioning: Systematic Review and Meta-analysis.

The current reference standard to check the position of a tubal sterilization microinsert device after its insertion is hysterosalpingography. The objective of this study was to evaluate the accuracy of 2-dimensional (2D) and 3-dimensional (3D) ultrasonography (US) in the positioning of the tubal sterilization microinsert for definitive contraception. We searched MEDLINE, Embase, Cochrane, and Scopus databases through October 2017. Selection criteria included studies that analyzed the accuracy of 2D or 3D US, or both, with respect to the positioning of the microinsert. Data were displayed as forest plots and a summary receiver operating characteristic curves. Values for sensitivity, specificity, and positive and negative likelihood ratios (LRs) were calculated. The pooled analysis produced sensitivity and specificity values for 2D US in the positioning of the microinsert of 0.88 (95% confidence interval [CI], 0.47-1.0) and 0.92 (95% CI, 0.88-0.95), respectively, with positive and negative LRs of 8.68 (95% CI, 1.63-46.1) and 0.35 (95% CI, 0.11-1.11), respectively. Three studies analyzed the performance of 3D US, showing sensitivity, specificity, and positive and negative LRs of 0.75 (95% CI, 0.35-0.97), 0.82 (95% CI, 0.77-0.87), 3.65 (95% CI, 2.31-5.75), and 0.46 (95% CI, 0.2-1.09). In conclusion, 2D and 3D US are methods that show good accuracy in tubal sterilization microinsert positioning.

Bisphenol A and polycystic ovary syndrome in human: A systematic review.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by anovulation, hyperandrogenism, and polycystic ovarian morphology. Its etiology is uncertain and one of the hypotheses is that environmental factors, such as the bisphenol A (BPA) endocrine disruptor, may be involved. OBJECTIVE: To investigate the association between exposure to BPA and PCOS. SEARCH STRATEGY: Research was conducted focusing on studies published in English, Portuguese, and Spanish from January 2001 to March 2023 and available in Embase, Medline/PubMed, Rima, Lilacs, Scielo, Google academic, and SCI databases. SELECTION CRITERIA: Studies in humans that evaluated the association between exposure to BPA and a diagnosis of PCOS. DATA COLLECTION AND ANALYSIS: Following PRISMA guidelines, study characteristics and relevant data were extracted. MAIN RESULTS: Selection of 15 case-control and 7 cross-sectional studies with a total of 1682 PCOS patients. The studies were carried out in China, Poland, Turkey, Japan, Greece, Italy, the USA, Iran, Iraq, Egypt, India, Czechia, and Slovakia. A positive relationship between exposure to BPA and PCOS was described in19 studies (1391 [82.70%] of the PCOS patients). The fluids used in the studies were serum, urine, plasma, and follicular fluid. BPA was measured by ELISA and by chromatography (HPLC, HPLC-MS/MS, GC-MS, and GC-MS/MS). Diagnosis of PCOS used Rotterdam criteria in 15, NIH 1999 in 3, AE&PCOS Society in 2, similar to the Rotterdam criteria in 1, and criteria not informed in 1. Androgens were measured in 16 studies; in 12, hyperandrogenism was positively associated with BPA. BPA level was related to body mass index (BMI) in studies. In 15 studies independently of BMI, women with PCOS had higher BPA levels. Carbohydrate metabolism disorders were evaluated in 12 studies and in 6 a positive correlation was found with BPA levels. Lipid profile was evaluated in seven studies and in only one the correlation between lipid profile and BPA levels was present. CONCLUSIONS: Exposure to BPA is positively associated with PCOS, mainly with the hyperandrogenism.

Hormonal and Metabolic Factors Influence the Action of Progesterone on the Endometrium of Women with Polycystic Ovary Syndrome.

Hormonal and metabolic factors may influence endometrial quality and interfere with the action of progesterone. Therefore, the aim of our study was to address this issue. Participants were recruited from an outpatient reproductive endocrinology clinic at an academic tertiary medical care centre. All subjects underwent endometrial biopsy (EB) in the follicular phase of the cycle prior to treatment. Thereafter, they were treated with micronized progesterone (400 mg/day × 10 days intravaginally) from days 14-28 of the next cycle. A second EB was performed between days 21-24 of the cycle (the second phase). The metabolic and hormonal serum levels were evaluated during the implantation window. EB samples were analysed using light microscopy for histomorphometric analysis. The endometrium of women with Polycystic Ovarian Syndrome (PCOS) in the second phase demonstrated a uniform surface epithelium with less leukocyte infiltration and an absence of apoptotic figures compared to the control group. (p < 0.021). The thickness of the surface epithelium in the second phase of the PCOS group correlated positively with free and bioavailable testosterone values. The number of stromal cells increases with increasing insulin levels. Our results suggest that histomorphometric abnormalities of the endometrium persist and are linked to androgen and insulin levels despite progesterone supplementation in PCOS.

Does bisphenol A (BPA) participates in the pathogenesis of Polycystic Ovary Syndrome (PCOS)?

PCOS is an endocrine disorder characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Its etiology is uncertain. It is debated whether BPA would be a component of the environmental factor in the etiology of PCOS. Contamination by BPA can occur from food packaging (exposure during the diet) and through skin absorption and/or inhalation. It can be transferred to the fetus via the placenta or to the infant via breast milk, and it can be found in follicular fluid, fetal serum, and amniotic fluid. The phenolic structure of BPA allows it to interact with Estrogen Receptors (ERs) through genomic signaling, in which BPA binds to nuclear ERα or Erß, or through nongenomic signaling by binding to membrane ERs, prompting a rapid and intense response. With daily and constant exposure, BPA's tendency to bioaccumulate and its ability to activate nongenomic signaling pathways can alter women's metabolic and reproductive function, leading to hyperandrogenism, insulin resistance, obesity, atherogenic dyslipidemia, chronic inflammatory state, and anovulation and favoring PCOS. The harmful changes caused by BPA can be passed on to future generations without the need for additional exposure because of epigenetic modifications. Not only high BPA levels can produce harmful effects, but at low levels, BPA may be harmful when exposure occurs during the most vulnerable periods, such as the fetal and neonatal periods, as well as during the prepubertal age causing an early accumulation of BPA in the body. Learning how BPA participates in the pathogenesis of PCOS poses a challenge and further studies should be conducted.

Effects of estrogen and raloxifene on synaptic density in the hippocampal CA1 region of ovariectomized rats.

INTRODUCTION: The CA1 region of the hippocampus has an important role in learning and memory. It has been shown that estrogen deficiency may reduce the synaptic density in the region and that hormone replacement therapy may attenuate the reduction. OBJECTIVES: This study aimed to evaluate the effects of estrogen and raloxifene on the synaptic density profile in the CA1 region of the hippocampus in ovariectomized rats. METHODS: Sixty ovariectomized three-month-old virgin rats were randomized into six groups (n = 10). Treatments started either three days (early treatment) or sixty days (late treatment) after ovariectomy. The groups received propylene glycol vehicle (0.5 mL/animal/day), equine conjugated estrogens (50 µg/animal/day), or raloxifene (3 mg/kg/day) either early or late after ovariectomy. The drugs were administered orally by gavage for 30 days. At the end of the treatments, the animals were anesthetized and transcardially perfused with ether and saline solution. The brains were removed and prepared for analysis under transmission electron microscopy and later fixed. RESULTS: Results showed a significant increase in the synaptic density profile of the hippocampal CA1 region in both the early estrogen (0.534 ± 0.026 µ/m2) and the early raloxifene (0.437 ± 0.012 µ/m2) treatment groups compared to the early or late vehicle-treated control groups (0.338 ± 0.038 µ/m2 and 0.277 ± 0.015 µ/m2 respectively). CONCLUSIONS: The present data suggest that the raloxifene effect may be lower than that of estrogen, even early or late treatment, on synaptic density in the hippocampus.

Association of intrauterine synechiae with pituitary gonadotrophin pulse patterns: A pilot study.

BACKGROUND: Intrauterine synechiae (IS) is an acquired uterine condition that occurs when scar tissues (adhesions) form within the uterus and/or cervix, causing menstrual disturbance. However, approximately 50% of patients with IS are refractory to treatment. Therefore, other endocrine disturbances, such as gonadotropin disturbance, may affect treatment success. STUDY AIM: To analyze gonadotropin levels in women with and without IS. METHODS: Ten women with refractory IS experiencing amenorrhea since at least 6 months and nine with normal menstrual cycles (control group) were included in this study. Blood sample were collected every 10 minutes during a 4-h period. The serial ultrasound was performed in both groups for evaluating the cycle phase. Blood was collected when the follicles size was between 5-10 mm. Serum LH, FSH, progesterone and estradiol concentrations were measured. To detect LH and FSH pulses, the technique proposed by Santen and Bardin was adopted; therefore, one pulse was defined as a 20% increase in the concentrations as to the preceding point, followed by an important decrease. RESULTS: No differences were observed between the study groups at baseline. Estradiol levels were lower in the IS group than in the control group, but the difference was not statistically significant. During the first hour of monitoring, cumulative FSH pulsatile frequency of IS group was lower than one of control. CONCLUSION: Our data suggest that the estradiol levels of IS participants are lower than those of women with normal menstrual cycle. The role of this finding in the physiology of uterine synechiae requires further investigation.

Does temporomandibular disorder correlate with menopausal symptoms?

OBJECTIVE: To assess the correlation between menopausal symptoms and pain caused by temporomandibular disorder (TMD) and the impact of sociodemographic factors on the association. METHODS: In this cross-sectional study, a total of 74 women with TMD symptoms were enrolled and divided into three groups according to the Stages of Reproductive Aging Workshop + 10 (STRAW + 10) criteria: G1 (n = 25, late menopausal transition), G2 (n = 30, early postmenopause), and G3 (n = 19, late postmenopause). Sociodemographic data were collected, along with data on menopausal symptoms (Blatt-Kupperman menopausal index) and TMD-induced pain (craniomandibular index). Statistical analysis was performed using a chi-squared test and linear correlation tests (Spearman and Pearson). RESULTS: Analysis of the three groups showed that TMD-induced pain was more intense in G1 than in G3 (P = 0.0426, r  = 0.2364, r2 = 0.05589), and menopausal symptoms correlated with the intensity of TMD-induced pain (P = 0.0004, r  = 0.4020). This correlation was more significant during the late menopausal transition (G1: P  = 0.0267, r  = 0.4427, r2 = 0.1960). In G2, women with fewer than 4 years of schooling had a higher total Blatt- Kupperman menopausal index score (17.0 ±â€Š85.0) and craniomandibular index (0.29 ±â€Š0.23) than women with more than 4 years of schooling (P  = 0.02 for both indices). CONCLUSIONS: Our results suggest that TMD-induced pain and menopausal symptoms are correlated, and more strongly so in the late menopausal transition. Additionally, sociodemographic factors, such as schooling, have a major influence on symptoms in early postmenopause. Performing the TMD evaluation during the climacteric period may be important.

Kisspeptin Influence on Polycystic Ovary Syndrome-a Mini Review.

Polycystic ovary syndrome (PCOS) affects 6% to 20% of reproductive age women and is the most frequent cause of anovulatory infertility. Its physiopathology may result in part from hypothalamic alterations in the pulsatile secretion of gonadotropin-releasing hormone (GnRH). The neuropeptide kisspeptin participates in the mechanism through stimulation of the hormone's production. The purpose of this study was to review the articles which compared kisspeptin levels in women with PCOS with those of controls. A systematic review of observational studies was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations. The selected studies encompassed a population of patients with PCOS and controls, whose serum kisspeptin levels were evaluated. The studies were retrieved from the Medline, Cochrane, and Embase databases, and four of them were chosen for the review. In most studies, the serum kisspeptin levels were higher in women with PCOS than in controls notwithstanding the BMI. One of the articles showed that circulating plasma levels of kisspeptin were significantly higher in women with PCOS whose BMI was lower than 25 than in obese and overweight women. Our data suggest a higher concentration of serum kisspeptin in women with PCOS irrespective of their BMI. Further experimental and clinical studies are needed to ascertain the role of kisspeptin in PCOS.

Evidence that Melatonin Increases Inhibin Beta-A and Follistatin Gene Expression in Ovaries of Pinealectomized Rats.

Melatonin plays an important role in the regulation of ovarian function including oocyte maturation in different mammalian species. Many studies indicate that melatonin has an impact on the ovarian function of a variety of ovarian cells. However, the information on the exact mechanism and involved hormones is low. To evaluate inhibin beta-A (INHBA) and follistatin (FST) expression in the ovaries of pinealectomized rats treated with melatonin, thirty adult female Wistar rats were randomized into three groups of ten animals each: group 1 (GSh), sham-operated controls receiving vehicle; group 2 (GPx), pinealectomized animals receiving vehicle; and group 3 (GPxMe), pinealectomized animals receiving replacement melatonin (1.0 mg/kg body weight. It was assumed that each animal drank 6.5 ± 1.2 ml per night and weighs approximately 300 g.) for 60 consecutive days. The ovaries were collected for mRNA abundance and protein of INHBA and FST by qRT-PCR and immunohistochemical analyses, respectively. Treatment with melatonin resulted in the upregulation of INHBA and FST genes in the ovarian tissue of the melatonin-treated animals (GPxMe), when compared with GPx. These findings were then confirmed by analyzing the expression of protein by immunohistochemical analyses, which revealed higher immunoreactivity of INHBA and FST in GPxMe animals in the follicular cells compared with GSh and GPx rats. Melatonin increases the expression of INHBA and FST in the ovaries of pinealectomized female rats.

Influence of age and gender on sex steroid receptors in rat masticatory muscles.

The temporomandibular muscle dysfunction is characterized by myofascial pain and is more prevalent in women of reproductive age. Sex steroid hormones are hypothetically involved in the dysfunction, but few are the studies of steroid receptors in masticatory and mastication-related muscles. Our aim was to determine estrogen and testosterone receptor expression in rat masticatory and mastication-related muscles within the context of age and gender. Twelve rats were equally divided into four groups: (a) 10-month-old females; (b) 10-month-old males; (c) 24-month-old females; and (d) 24-month-old males. Euthanasia of the females was performed in the proestrous phase (vaginal smears) and the masticatory and accessory muscles were removed for immunohistochemical analysis. Statistical analysis was performed with ANOVA and the Tukey test. Estrogen receptor expression was similarly low in all muscles and groups. Testosterone receptor expression in the Masseter muscle of the 24-month-old male rats was higher than that in the other groups and significantly superior to its expression in the Posterior Digastric muscle. In short, testosterone receptor expression was highest in old male rats. If we generalize to humans, this fact could indicate age- and sex-related hormonal influence on temporomandibular muscle dysfunction. Further studies, however, are necessary to strengthen this hypothesis.

Melatonin effects on ovarian follicular cells: a systematic review.

Melatonin is known for its effects on both the sleep and reproductive system of mammals. The latter has melatonin receptors type 1 and 2, which act to regulate, among other things, cyclic AMP. Notwithstanding all the literature data, there is still no sound knowledge or a clear understanding of the hormone's action on the physiology of ovarian follicular cells. OBJECTIVE To review and evaluate studies about melatonin action on the ovarian granulosa/theca interna cells from the literature. METHODS The systematic review was carried out according to the PRISMA recommendations. The MEDLINE and Cochrane primary databases were consulted with the use of specific terms. There was no limitation on language or publication year. RESULTS Seven papers about melatonin action on granulosa cells were selected. The following can be attributed to the hormone's effects: a) progesterone increase in culture medium; b) increased estrogen production; c) antagonistic action on estrogen; d) improvement in cell quality resulting in improved embryo and higher pregnancy rates; e) improved cell proliferation via MAPK; f) reduction of free radicals. Nevertheless, there are contrarian papers reporting a reduction in progesterone production. Melatonin interferes in sex steroid production, boosting progesterone output. Such action may help improve oocyte quality.

Metformin improves ovarian follicle dynamics by reducing theca cell proliferation and CYP-17 expression in an androgenized rat model.

BACKGROUND: Metformin influences insulin receptor signaling, which might interfere with the proliferation of ovarian follicular structures and steroidogenesis. We hypothesize that reductions in glucose and insulin levels might interfere with CYP-17 expression and histomorphological changes in an androgenized rat model. The aim of this study was to analyze the effect of metformin on CYP-17 expression, follicular dynamics, and proliferative parameters in neonatally androgenized female rats. METHODS: Thirty-six newborn rats were randomly allocated to the following three groups on the third day of life: control (CG, n = 12), androgenized (GA, n = 12), and androgenized + metformin (GAmet, n = 12). The GA and GAmet animals were administered 0.1 mL of testosterone propionate (1.25 mg/animal) diluted in castor oil (vehicle) in a single dose; the CG rats received a subcutaneous injection of the vehicle in the dorsum. After 90 days, gavage treatment was initiated, distilled water was administered to the CG and GA rats, and metformin (150 mg/kg) was administered to the GAmet animals. The treatment was administered daily for six weeks. Following anesthesia, blood was drawn for biochemical measurements, and the ovaries were removed for histological and immunohistochemical analyses of Ki67, VEGFA and CYP17 expression. The glucose and insulin levels were also measured. RESULTS: The comparison of the GA and GAmet animals revealed that metformin decreased the weight as well as the glucose and insulin levels, slowed the proliferation of the theca interna and interstitial cells, as evidenced by Ki-67 and VEGF-A expression, and diminished CYP17 expression in the analyzed ovarian structures. In addition, metformin reduced the number of degenerating follicles and interstitial cells and improved angiogenesis. CONCLUSION: Metformin improves the carbohydrate metabolism, reduces proliferation, and decreases CYP-17 expression in the follicular structures of androgenized rats.

Does bisphenol A (BPA) participates in the pathogenesis of Polycystic Ovary Syndrome (PCOS)?

Abstract PCOS is an endocrine disorder characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Its etiology is uncertain. It is debated whether BPA would be a component of the environmental factor in the etiology of PCOS. Contamination by BPA can occur from food packaging (exposure during the diet) and through skin absorption and/or inhalation. It can be transferred to the fetus via the placenta or to the infant via breast milk, and it can be found in follicular fluid, fetal serum, and amniotic fluid. The phenolic structure of BPA allows it to interact with Estrogen Receptors (ERs) through genomic signaling, in which BPA binds to nuclear ERα or Erβ, or through nongenomic signaling by binding to membrane ERs, prompting a rapid and intense response. With daily and constant exposure, BPA's tendency to bioaccumulate and its ability to activate nongenomic signaling pathways can alter women's metabolic and reproductive function, leading to hyperandrogenism, insulin resistance, obesity, atherogenic dyslipidemia, chronic inflammatory state, and anovulation and favoring PCOS. The harmful changes caused by BPA can be passed on to future generations without the need for additional exposure because of epigenetic modifications. Not only high BPA levels can produce harmful effects, but at low levels, BPA may be harmful when exposure occurs during the most vulnerable periods, such as the fetal and neonatal periods, as well as during the prepubertal age causing an early accumulation of BPA in the body. Learning how BPA participates in the pathogenesis of PCOS poses a challenge and further studies should be conducted.

Effects of estrogen and raloxifene on synaptic density in the hippocampal CA1 region of ovariectomized rats

Abstract Introduction The CA1 region of the hippocampus has an important role in learning and memory. It has been shown that estrogen deficiency may reduce the synaptic density in the region and that hormone replacement therapy may attenuate the reduction. Objectives This study aimed to evaluate the effects of estrogen and raloxifene on the synaptic density profile in the CA1 region of the hippocampus in ovariectomized rats. Methods Sixty ovariectomized three-month-old virgin rats were randomized into six groups (n = 10). Treatments started either three days (early treatment) or sixty days (late treatment) after ovariectomy. The groups received propylene glycol vehicle (0.5 mL/animal/day), equine conjugated estrogens (50 μg/animal/day), or raloxifene (3 mg/kg/day) either early or late after ovariectomy. The drugs were administered orally by gavage for 30 days. At the end of the treatments, the animals were anesthetized and transcardially perfused with ether and saline solution. The brains were removed and prepared for analysis under transmission electron microscopy and later fixed. Results Results showed a significant increase in the synaptic density profile of the hippocampal CA1 region in both the early estrogen (0.534 ± 0.026 µ/m2) and the early raloxifene (0.437 ± 0.012 µ/m2) treatment groups compared to the early or late vehicle-treated control groups (0.338 ± 0.038 µ/m2 and 0.277 ± 0.015 µ/m2 respectively). Conclusions The present data suggest that the raloxifene effect may be lower than that of estrogen, even early or late treatment, on synaptic density in the hippocampus.

Small leucine-rich proteoglycans (SLRPs) in the endometrium of polycystic ovary syndrome women: a pilot study.

BACKGROUND: Small leucine-rich proteoglycans (SLRPs) play an important role in tissue homeostasis and cell proliferation since these proteoglycans sequester multiple growth factors. However, the content of SLRPs in the endometrium of polycystic ovary syndrome (PCOS) women is unknown. Our purpose was to test the hypothesis that excessive endometrial proliferation in PCOS may be partly related to abnormalities in SLRPs. METHODS: In a cross section study a total of 20 endometrial samples were collected from 10 patients with PCOS and 10 ovulatory women during their proliferative (pre-ovulatory) phase. The study subjects were matched for age, body mass index and race. The age range was 20 to 35 years. All volunteers were evaluated in reproductive endocrinology clinic, Gynecology Division, Clinics Hospital, University of São Paulo Medical School Profile and concentration of small leucine-rich proteoglycans (decorin, lumican, fibromodulin and biglycan) were determined by immunohistochemical testing and Western blotting. RESULTS: Decorin and lumican demonstrated higher immunoreactivity and relative expression in the endometrium of women with PCOS compared to that of women with regular menstrual cycles. CONCLUSION: Our data suggests that the endometrium of PCOS women demonstrate a greater content of SLRP than controls; decorin and lumican, in particular, were found in higher concentrations in the endometrium of PCOS women during the proliferative phase. These differences may, in part, explain the excess of endometrial proliferation frequently observed in PCOS. Further studies are warranted.

Osteoporosis and autophagy: What is the relationship?

Autophagy is a survival pathway wherein non-functional proteins and organelles are degraded in lysosomes for recycling and energy production. Therefore, autophagy is fundamental for the maintenance of cell viability, acting as a quality control process that prevents the accumulation of unnecessary structures and oxidative stress. Increasing evidence has shown that autophagy dysfunction is related to several pathologies including neurodegenerative diseases and cancer. Moreover, recent studies have shown that autophagy plays an important role for the maintenance of bone homeostasis. For instance, in vitro and animal and human studies indicate that autophagy dysfunction in bone cells is associated with the onset of bone diseases such as osteoporosis. This review had the purpose of discussing the issue to confirm whether a relationship between autophagy dysfunction and osteoporosis exits.

Síndrome dos ovários policísticos e sua relação com a microbiota intestinal / Polycystic ovary syndrome and its relationship with the intestinal microbiota

Objetivo: Revisar a implicação e a relação existente entre a microbiota intestinal e a síndrome do ovário policístico (SOP). Métodos: Trata-se de uma revisão sistemática de artigos das bases de dados PubMed, Cochrane e Science Direct dos últimos cinco anos, nos idiomas inglês, português e espanhol. Resultados: A disbiose da microbiota intestinal ativa o sistema imunológico do hospedeiro. Tal ativação interfere na função do receptor de insulina, causando hiperinsulinemia, o que aumenta a produção de androgênio ovariano e dificulta o desenvolvimento de um folículo saudável. Além disso, pacientes com SOP apresentam o perfil taxonômico alterado, o qual se associou inversamente com excesso de andrógenos e inflamação da SOP. Foi evidenciado que o uso de probióticos pode regular a resposta inflamatória, diminuir os níveis totais de testosterona e contribuir para que a SOP não prejudique uma possível gravidez. Conclusão: Essa revisão sugere que há íntima associação entre a disbiose microbiana e as alterações patológicas que ocorrem na SOP. Assim, a suplementação de probióticos em tais pacientes pode ter grandes benefícios, como melhora dos sintomas e redução das repercussões da doença.(AU)

Objective: To review the implication and the relationship between the intestinal microbiota and polycystic ovary syndrome. Methods: This is a systematic review of articles from the PubMed, Cochrane and Science Direct databases, from the last five years, in English, Portuguese and Spanish. Results: Dysbiosis of the intestinal microbiota activates the host's immune system. Such activation interferes with the function of the insulin receptor, causing hyperinsulinemia, which increases the production of ovarian androgens and hinders the development of a healthy follicle. In addition, patients with PCOS have an altered taxonomic profile, which is inversely associated with excess androgens and PCOS inflammation. It was evidenced that the use of probiotics can regulate the inflammatory response, decrease the total testosterone levels and contribute so that PCOS does not harm a possible pregnancy. Conclusion: This review suggests that there is a close association between microbial dysbiosis and pathological changes that occur in PCOS. Thus, supplementation of probiotics in such patients can have great benefits, such as improving symptoms and reducing the repercussions of the disease.(AU)