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.

Reproductive outcomes in cases of subclinical hypothyroidism and thyroid autoimmunity: a narrative review / Resultados reprodutivos nos casos de hipotireoidismo subclínico e autoimunidade tireoidiana: Uma revisão narrativa

Abstract Thyroid diseases are relatively common in women in the reproductive period. It is currently understood that clinically-evident thyroid disorders may impair ovulation and, consequently, fertility. However, to date it has not been proven that high serum levels of thyroid-stimulating hormone and/or positivity for antithyroid antibodies are associated to a reduction in fertility, mainly in the absence of altered thyroxine levels. The present comprehensive review aims to present current data on the association between subclinical hypothyroidism and/or thyroid autoimmunity and reproductive outcomes.

Resumo As doenças da tireoide são relativamente comuns em mulheres no período reprodutivo. Atualmente, entende-se que distúrbios da tireoide clinicamente evidentes podem prejudicar a ovulação e, consequentemente, a fertilidade. No entanto, não se provou até o presente que níveis séricos altos do hormônio estimulador da tireoide e/ou positividade para anticorpos antitireoidianos estão associados a uma redução na fertilidade, sobretudo na ausência de níveis alterados de tiroxina. Esta revisão narrativa tem como objetivo apresentar dados atuais sobre a associação entre hipotireoidismo subclínico e/ou autoimunidade tireoidiana e resultados reprodutivos.

Repercussões metabólicas e uso dos medicamentos sensibilizadores da insulina em mulheres com síndrome dos ovários policísticos / Metabolic repercussions and use of insulin-sensitizing drugs in women with polycystic ovary syndrome

A síndrome dos ovários policísticos (SOP) é um distúrbio endócrino-metabólico muito frequente no período reprodutivo. Quando associado ao distúrbio metabólico, as mulheres com SOP podem ter ainda risco acrescido para doença cardiovascular. O objetivo deste manuscrito é descrever as repercussões metabólicas, incluindo quais as principais, como investigar e as consequências desse distúrbio sobre a saúde da mulher. É uma revisão narrativa mostrando a implicação da resistência insulínica, das dislipidemias e da síndrome metabólica sobre o sistema reprodutor e sobre o risco cardiovascular da mulher com SOP, bem como do uso de sensibilizadores de insulina no seu tratamento. Conclui-se que a correção dos distúrbios metabólicos na SOP é benéfica tanto para o sistema reprodutor quanto para o cardiovascular. A primeira linha de tratamento é a mudança de estilo de vida e a perda de peso. Na resposta inadequada, o tratamento medicamentoso está recomendado. Nas mulheres com obesidade mórbida que não tiveram bons resultados com o tratamento clínico, a cirurgia bariátrica é uma opção.(AU)

Increasing the chances of natural conception: opinion statement from the the brazilian federation of gynecology and obstetrics associations - FEBRASGO committee of gynecological endocrinology / Aumentando as chances de concepção natural: parecer da comissão nacional de ginecologia endócrina da Federação Brasileira das Associações de Ginecologia e Obstetrícia

Abstract Considering that myths and misconceptions regarding natural procreation spread rapidly in the era of easy access to information and to social networks, adequate counseling about natural fertility and spontaneous conception should be encouraged in any kind of health assistance. Despite the fact that there is no strong-powered evidence about any of the aspects related to natural fertility, literature on how to increase the chances of a spontaneous pregnancy is available. In the present article, the Brazilian Federation of Gynecology and Obstetrics Associations (FEBRASGO, in the Portuguese acronym) Committee on Endocrine Gynecology provides suggestions to optimize counseling for non-infertile people attempting spontaneous conception.

Resumo Uma vez que mitos e equívocos sobre a procriação natural se espalham rapidamente na era do fácil acesso à informação e às redes sociais, o aconselhamento adequado sobre a fertilidade natural e a concepção espontânea deve ser encorajado em qualquer tipo de assistência à saúde. Apesar do fato de não haver evidências fortes sobre qualquer dos aspectos relacionados à fertilidade natural, existe literatura sobre como aumentar as chances de uma gravidez espontânea. No presente artigo, a Comissão Nacional de Ginecologia Endócrina da Federação Brasileira das Associações de Ginecologia e Obstetrícia (FEBRASGO) oferece sugestões para otimizar o aconselhamento a pessoas que tentam a concepção espontânea, na ausência do diagnóstico de infertilidade.

Recommendations for the use of testosterone in male transgender / Recomendações para o uso da testosterona em homens transgêneros

Abstract Gender incongruence is defined as a condition in which an individual self-identifies and desires to have physical characteristics and social roles that connote the opposite biological sex. Gender dysphoria is when an individual displays the anxiety and/or depression disorders that result from the incongruity between the gender identity and the biological sex. The gender affirmation process must be performed by a multidisciplinary team. The main goal of the hormone treatment is to start the development of male physical characteristics by means of testosterone administration that may be offered to transgender men who are 18 years old or over. The use of testosterone is usually well tolerated and improves the quality of life. However, there is still lack of evidence regarding the effects and risks of the long-term use of this hormone. Many different pharmacological formulations have been used in the transsexualization process. The most commonly used formulation is the intramuscular testosterone esters in a short-term release injection, followed by testosterone cypionate or testosterone enanthate. In the majority of testosterone therapy protocols, the male physical characteristics can be seen in almost all users after 6 months of therapy, and themaximum virilization effects are usually achieved after 3 to 5 years of regular use of the hormone. To minimize risks, plasmatic testosterone levels should be kept within male physiological ranges (300 to 1,000 ng/dl) during hormonal treatment. It is recommended that transgender men under androgen therapy be monitored every 3 months during the 1st year of treatment and then, every 6 to 12 months.

Resumo Incongruência de gênero é umacondição na qual o indivíduo se identifica, deseja viver e ser aceito como uma pessoa do gênero oposto ao designado por ocasião do nascimento. Na disforia de gênero o indivíduo manifesta ansiedade e sofrimento pelo desejo de viver e ser aceito como uma pessoa do gênero oposto ao designado ao nascimento. O processo transsexualizador requer trabalho em equipe multiprofissional. O objetivo do tratamento hormonal é induzir o aparecimento de características sexuais masculinas secundárias por meio da administração da testosterona em indivíduos com idade igual ou superior a 18 anos. O tratamento de estimulação androgênica costuma ser bem tolerado. Entretanto, ainda não existemevidências sobre os efeitos e riscos do uso da testosterona a longo prazo. Diferentes preparações farmacológicas da testosterona têm sido utilizadas. As mais utilizadas têm sido as injeções intramusculares de administração a curto prazo de ésteres, seguidas do cipionato de testosterona e do enantato de testosterona. Na maioria dos protocolos de tratamento observa-se o aparecimento de características corporais masculinas nos primeiros 6 meses, e a obtenção do máximo efeito da estimulação androgênica, após 3 a 5 anos de uso regular da testosterona. Recomenda-se a manutenção dos níveis plasmáticos de testosterona dentro dos limites fisiológicos para o sexo masculino (300 a 1.000 ng/dl), a fim de minimizar os riscos. A monitorização dos homens transgênero é recomendada a cada 3meses durante o primeiro ano de tratamento e a seguir, a cada 6 a 12 meses.

Avaliação da reserva ovariana na predição do mau prognóstico reprodutivo: quando e como investigar / Ovarian reserve evaluation in the prediction of poor reproductive prognosis: when and how to investigate?

Muitas vezes, torna-se um grande desafio para o ginecologista a identificação daquelas com maior ou menor chance de concepção. Vários marcadores laboratoriais e ultrassonográficos, conhecidos conjuntamente como testes de avaliação da reserva ovariana, são estudados há décadas com a intenção de se buscar uma ferramenta para a predição do potencial reprodutivo. E, embora ainda se busquem os marcadores ideais para aplicação clínica, mais difícil do que os definir é definir quando eles estão indicados. Este artigo de atualização, assinado pela Comissão Nacional Especializada em Ginecologia Endócrina da Febrasgo, pretende oferecer ao leitor as ferramentas necessárias para o uso racional dos testes de avaliação da reserva ovariana no cotidiano.(AU)

Often, it becomes a great challenge for the gynecologist to identify women with a greater or lesser chance of conception. Several laboratory and ultrasound markers, known jointly as ovarian reserve evaluation tests, have been studied for decades with the intention of seeking a tool for the prediction of reproductive potential. And, while the ideal markers for clinical application are still sought, defining them is as harder as defining when they are indicated. This update article, signed by the National Specialized Committee on Gynecologic Endocrinology, Febrasgo, intends to offer the reader the necessary tools for the rational use of ovarian reserve evaluation tests in daily practice.(AU)

Hypothalamic transcriptional expression of the kisspeptin system and sex steroid receptors differs among polycystic ovary syndrome rat models with different endocrine phenotypes

OBJECTIVES: Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects reproductive-age women. The mechanisms underlying the endocrine heterogeneity and neuroendocrinology of polycystic ovary syndrome are still unclear. In this study, we investigated the expression of the kisspeptin system and gonadotropin-releasing hormone pulse regulators in the hypothalamus as well as factors related to luteinizing hormone secretion in the pituitary of polycystic ovary syndrome rat models induced by testosterone or estradiol. METHODS: A single injection of testosterone propionate (1.25 mg) (n=10) or estradiol benzoate (0.5 mg) (n=10) was administered to female rats at 2 days of age to induce experimental polycystic ovary syndrome. Controls were injected with a vehicle (n=10). Animals were euthanized at 90-94 days of age, and the hypothalamus and pituitary gland were used for gene expression analysis. RESULTS: Rats exposed to testosterone exhibited increased transcriptional expression of the androgen receptor and estrogen receptor-β and reduced expression of kisspeptin in the hypothalamus. However, rats exposed to estradiol did not show any significant changes in hormone levels relative to controls but exhibited hypothalamic downregulation of kisspeptin, tachykinin 3 and estrogen receptor-α genes and upregulation of the gene that encodes the kisspeptin receptor. CONCLUSIONS: Testosterone- and estradiol-exposed rats with different endocrine phenotypes showed differential transcriptional expression of members of the kisspeptin system and sex steroid receptors in the hypothalamus. These differences might account for the different endocrine phenotypes found in testosterone- and estradiol-induced polycystic ovary syndrome rats.

A prospective randomized study of the inflammatory responses to multiport and singleport laparoscopic hysterectomies

Abstract Purpose: To evaluate the inflammatory responses induced by laparoscopic hysterectomies with multiport and singleport approaches. Methods: This was a pilot prospective randomized study that included 42 women candidates for hysterectomy at School of Medicine, Hospital das Clínicas, USP. The patients were randomized to two groups: MP-TLH (total laparoscopic hysterectomy with 3 abdominal incisions), and SP-TLH (total laparoscopic hysterectomy with a single umbilical incision).We evaluated the inflammatory response (via CRP, IL-6, IL-10, TNFα, VEGF and leukogram assessments), surgical time, postoperative pain, blood loss and surgical complications in both groups. Results: Both techniques were similar regarding C-reactive protein (p=.666), IL-6 (p=.833), IL-10 (p=.420), TNF-α(p=.098), VEGF (p=.092) and the leukogram (p=.712) measures. The operative time was significantly longer in the SP-TLH group than in the MP-TLH group (p=.001). The pain evaluation was similar in both groups (p=.170). Hemoglobin variation and the aspirated blood volume were similar in both groups (p=.493 and p=.347). There were no major complications. Conclusions: Multiport and singleport laparoscopic approaches are both safe methods for hysterectomy. Although SP-TLH resulted in a significantly longer operative time than MP-TLH, no differences were observed between the groups in inflammatory responses, blood loss and postoperative pain.

Memory deficit associated with increased brain proinflammatory cytokine levels and neurodegeneration in acute ischemic stroke / Déficit de memória associado ao aumento dos níveis cerebrais de citocinas pró-inflamatórias e neurodegeneração na isquemia cerebral aguda

The present study aimed to investigate behavioral changes and neuroinflammatory process following left unilateral common carotid artery occlusion (UCCAO), a model of cerebral ischemia. Post-ischemic behavioral changes following 15 min UCCAO were recorded 24 hours after reperfusion. The novel object recognition task was used to assess learning and memory. After behavioral test, brains from sham and ischemic mice were removed and processed to evaluate central nervous system pathology by TTC and H&E techniques as well as inflammatory mediators by ELISA. UCCAO promoted long-term memory impairment after reperfusion. Infarct areas were observed in the cerebrum by TTC stain. Moreover, the histopathological analysis revealed cerebral necrotic cavities surrounded by ischemic neurons and hippocampal neurodegeneration. In parallel with memory dysfunction, brain levels of TNF-a, IL-1b and CXCL1 were increased post ischemia compared with sham-operated group. These findings suggest an involvement of central nervous system inflammatory mediators and brain damage in cognitive impairment following unilateral acute ischemia.

O presente estudo teve como objetivo investigar alterações comportamentais e processos inflamatórios na isquemia cerebral induzida pela oclusão unilateral da carótida comum esquerda (UCCAO) em camundongos. As alterações comportamentais foram avaliadas após 15 minutos de isquemia e 24 horas de reperfusão. O teste de reconhecimento de objetos foi utilizado para avaliação da memória e do aprendizado. Em seguida, os animais foram mortos e os encéfalos foram coletados e processados para avaliação das alterações patológicas pelas técnicas de TTC e H&E, assim como da dosagem de mediadores inflamatórios por ELISA. A UCCAO promoveu alterações de memória após a reperfusão. Foram visualizadas áreas de infarto cerebral pela coloração de TTC e cavidades necróticas circundadas por neurônios isquêmicos no cérebro e neurodegeneração hipocampal. A UCCAO causou aumento dos níveis encefálicos de TNF-a, IL-1b e CXCL1. Estes achados demonstraram o envolvimento dos mediadores inflamatórios no sistema nervoso central e da neurodegeneração no déficit cognitivo após isquemia cerebral aguda.

Mast cell concentration and skin wound contraction in rats treated with Brazilian pepper essential oil (Schinus terebinthifolius Raddi)

PURPOSE: To evaluate wound contraction and the concentration of mast cells in skin wounds treated with 5% BPT essential oil-based ointment in rats. METHODS: Twenty rats, male, of adult age, were submitted to skin surgery on the right (RA) and left antimeres (LA) of the thoracic region. They were divided into two groups: control (RA - wounds receiving daily topical application of vaseline and lanolin) and treated (LA - wounds treated daily with the topical ointment). The skin region with wounds were collected at days 4, 7, 14 and 21 after surgery. Those were fixed in 10% formaldehyde and later processed for paraffin embedding. Sections were obtained and stained by H.E for histopathology analysis. The degree of epithelial contraction was measured and mast cell concentration were also evaluated. RESULTS: The treated group showed higher mast cell concentrations (p<0.05) associated with increased contraction at day 7 and 14 respectively. CONCLUSION: Ointment containing 5% Brazilian pepper tree oil increases mast cell concentration and promotes skin wound contraction in rats. .

Sympathetic glial cells and macrophages develop different responses to Trypanosoma cruzi infection or lipopolysaccharide stimulation

Nitric oxide (NO) participates in neuronal lesions in the digestive form of Chagas disease and the proximity of parasitised glial cells and neurons in damaged myenteric ganglia is a frequent finding. Glial cells have crucial roles in many neuropathological situations and are potential sources of NO. Here, we investigate peripheral glial cell response to Trypanosoma cruzi infection to clarify the role of these cells in the neuronal lesion pathogenesis of Chagas disease. We used primary glial cell cultures from superior cervical ganglion to investigate cell activation and NO production after T. cruzi infection or lipopolysaccharide (LPS) exposure in comparison to peritoneal macrophages. T. cruzi infection was greater in glial cells, despite similar levels of NO production in both cell types. Glial cells responded similarly to T. cruzi and LPS, but were less responsive to LPS than macrophages were. Our observations contribute to the understanding of Chagas disease pathogenesis, as based on the high susceptibility of autonomic glial cells to T. cruzi infection with subsequent NO production. Moreover, our findings will facilitate future research into the immune responses and activation mechanisms of peripheral glial cells, which are important for understanding the paradoxical responses of this cell type in neuronal lesions and neuroprotection.

Morphology and immunohistochemistry of the myenteric plexus of valves constructed in the colon of rats submitted to abdominoperineal amputation and perineal colostomy

PURPOSE: To investigate immunohistochemical aspects of the myenteric plexus of valves constructed in the colon of rats to verify whether any denervation occurs both at the operative site and in those areas adjacent to the third valve. METHODS: Thirty six male Wistar rats divided into the following three groups were used: Control Group (CG); Amputated Group (AG); Amputated Group with Valves (AGWV). In AG was held in the rectum amputation and the colon was sutured to the skin elaborating the perineal colostomy. In AGWV was held in the rectum amputation. A laparotomy was performed for the manufacture of valves (seromyotomy) in the colon. After this step, the colon was sutured to the skin elaborating the perineal colostomy. The density of the neural elements in the muscular wall as marked specifically using Protein Gene Product (PGP) 9.5 and utilising the proper tools of the KS300 software for measuring the area. From these measurements, a relation and three proportions were drawn and analysed according to the mean of the averages obtained from the measured images. RESULTS: Immunoexpression of PGP 9.5 demonstrated a total absence of neural elements and myenteric plexus at the valve site. The density of the neural elements in the circular muscular layer at sites adjacent to the 3rd valve was lesser, however, was not significantly different. CONCLUSION: The immunohistochemical study of valves constructed in the colon of rats submitted to abdominoperineal amputation and perineal colostomy revealed denervation at the seromyotomy site.