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.

Association of Overweight and Consistent Anovulation among Infertile Women with Regular Menstrual Cycle: A Case-control Study.

OBJECTIVE: It has been suggested that excess body weight could represent a risk factor for infertility outcomes. The present study aimed to evaluate the association of overweight and anovulation among infertile women with regular menstrual cycles. METHODS: We conducted a retrospective case-control study with consistently anovulatory patients undergoing assisted reproduction treatment. The patients were stratified into normal weight (body mass index [BMI]: 18.5-24.9kg/m2) and overweight (BMI: 25.0-29.9kg/m2).Those with polycystic ovary syndrome or obesity were excluded. The groups were matched for age, duration of infertility, prolactin, follicle stimulating hormone (FSH), thydroid stimulating hormone (TSH), luteinizing hormone (LH), and estradiol levels. RESULTS: Overweight was significantly associated with anovulation, when using the World Health Organization (WHO) criteria for anovulation: progesterone levels > 5.65 ng/ml and ultrasonography evidence of follicle collapse (odds ratio [OR]: 2.69; 95% confidence interval [CI95%]: 1.04-6.98). CONCLUSION: Body mass index above the normal range jeopardizes ovulation among non-obese infertile women with regular menstrual cycles.

OBJETIVO: O excesso de peso corporal tem sido associado como fator de risco para infertilidade. Este estudo teve como objetivo avaliar a associação de sobrepeso e anovulação entre mulheres inférteis com ciclos menstruais regulares. MéTODOS: Realizamos um estudo retrospectivo de caso-controle com mulheres com anovulação consistente em tratamento por reprodução assistida. As pacientes foram estratificadas entre aquelas com peso normal (índice de massa corporal [IMC]: 18,5­24,9 Kg/m2) e as com sobrepeso (IMC: 25,0­29,9 Kg/m2). As pacientes com síndrome do ovário policístico ou obesidade foram excluídas. Os grupos foram pareados por idade, duração da infertilidade, níveis de prolactina, hormônio folículo-estimulante (FSH), hormônio tiroestimulante (TSH), hormônio luteinizante (LH) e estradiol. RESULTADOS: O excesso de peso associou-se significativamente à anovulaçãoquando usados os critérios de anovulação da Organização Mundial de Saúde (OMS): níveis de progesterona > 5,65 ng/ml e evidência ultrassonográfica de colapso folicular (razão de chances [RC]: 2,69; IC95%: 1,04­6,98). CONCLUSãO: O IMC acima da faixa normal compromete a ovulação em mulheres inférteis não obesas com ciclos menstruais regulares.

Association of Overweight and Consistent Anovulation among Infertile Women with Regular Menstrual Cycle: A Case-control Study / Associação entre sobrepeso e anovulação consistente em mulheres inférteis com ciclo menstrual regular: Um estudo de caso-controle

Abstract Objective It has been suggested that excess body weight could represent a risk factor for infertility outcomes. The present study aimed to evaluate the association of overweight and anovulation among infertile women with regular menstrual cycles. Methods We conducted a retrospective case-control study with consistently anovulatory patients undergoing assisted reproduction treatment. The patients were stratified into normal weight (body mass index [BMI]: 18.5-24.9kg/m2) and overweight (BMI: 25.0- 29.9kg/m2).Those with polycystic ovary syndrome or obesity were excluded. The groups were matched for age, duration of infertility, prolactin, follicle stimulating hormone (FSH), thydroid stimulating hormone (TSH), luteinizing hormone (LH), and estradiol levels. Results Overweight was significantly associated with anovulation, when using the World Health Organization (WHO) criteria for anovulation: progesterone levels>5.65 ng/ml and ultrasonography evidence of follicle collapse (odds ratio [OR]: 2.69; 95% confidence interval [CI95%]: 1.04-6.98). Conclusion Body mass index above the normal range jeopardizes ovulation among non-obese infertile women with regular menstrual cycles.

Resumo Objetivo O excesso de peso corporal tem sido associado como fator de risco para infertilidade. Este estudo teve como objetivo avaliar a associação de sobrepeso e anovulação entre mulheres inférteis com ciclos menstruais regulares. Métodos Realizamos um estudo retrospectivo de caso-controle com mulheres com anovulação consistente em tratamento por reprodução assistida. As pacientes foram estratificadas entre aquelas com peso normal (índice de massa corporal [IMC]: 18,5- 24,9 Kg/m2) e as com sobrepeso (IMC: 25,0-29,9 Kg/m2). As pacientes com síndrome do ovário policístico ou obesidade foram excluídas. Os grupos foram pareados por idade, duração da infertilidade, níveis de prolactina, hormônio folículo-estimulante (FSH), hormônio tiroestimulante (TSH), hormônio luteinizante (LH) e estradiol. Resultados O excesso de peso associou-se significativamente à anovulaçãoquando usados os critérios de anovulação da Organização Mundial de Saúde (OMS): níveis de progesterona>5,65 ng/ml e evidência ultrassonográfica de colapso folicular (razão de chances [RC]: 2,69; IC95%: 1,04-6,98). Conclusão O IMC acima da faixa normal compromete a ovulação em mulheres inférteis não obesas com ciclos menstruais regulares.

Successful pregnancy after ovulation induction with human chorionic gonadotropin in a woman with selective luteinising hormone deficiency.

Selective LH deficiency has been described in several men, but only in two women who presented normal pubertal development but secondary amenorrhoea due to anovulation. Despite its rarity, this condition represents a valuable model for studying the processes regulated by FSH or LH during late folliculogenesis and ovulation in humans. A woman previously diagnosed with selective LH deficiency due to a homozygous germline splice site mutation in LHB (IVS2 + 1G→C mutation) was submitted to an individualised ovarian induction protocol, first with recombinant LH and then with highly purified urinary hCG. Ovarian follicle growth and ovulation were achieved, and a healthy baby was born after an uneventful term pregnancy. The treatment described herein demonstrates that the clinical actions of exogenous LH or hCG in inducing late-stage follicular development in women with deficient LH production or performance might be interchangeable or inevitable, once FSH-dependent early follicular growth is assured.

Síndrome de ovario poliquístico e infertilidad / Polycystic ovary syndrome and infertility

Una de las manifestaciones del síndrome de ovario poliquístico (SOP) es la infertilidad, y hoy es la primera causa de infertilidad por anovulación, representando aproximadamente el 80% de los casos. Las alteraciones del SOP en su mayoría son tratables y el diagnóstico temprano de las pacientes mejora su pronóstico reproductivo. Pese a su alta incidencia e importancia, los mecanismos fisiopatológicos del SOP aún son relativamente desconocidos. Recientemente se han publicado recomendaciones internacionales basadas en evidencia para su tratamiento.

Infertility is one of the main manifestations of the polycystic ovary syndrome (PCOS), and to day PCOS is the main cause of anovulatory infertility accounting for 80% of the cases. The majority of PCOS causes of infertility are treatable, and early diagnosis improves the patient's fertility outcome. In spite of its incidence and importance, the physiopathological mechanisms of PCOS are still relatively unknown. Recently an international evidence base recommendation for treatment have been published.

Oxygen saturation during sleep as a predictor of inflammation in anovulatory women.

PURPOSE: To evaluate the inflammatory profile of premenopausal women with anovulatory cycles, regular menstrual cycles, or using contraceptives, and the associations with sleep and health-related parameters. METHODS: Subjects completed questionnaires including the Pittsburgh Sleep Quality Index and the Epworth sleepiness scale, underwent whole-night polysomnography, and had blood collected for analysis of inflammatory, cardiovascular, and hormonal parameters. Women of reproductive age were categorized into three groups for comparisons: anovulatory menstrual cycles, regular menstrual cycles, and hormonal contraceptive use. RESULTS: Women with anovulatory menstrual cycles (n = 20) had higher circulating levels of the proinflammatory cytokine IL-6 compared with women who had regular menstrual cycles (n = 191) and those on hormonal contraception (n = 72). No other classical marker of low-grade inflammation was significantly different. Subjective and objective sleep data were similar among groups. However, the mean peripheral oxygen saturation (SpO2) during sleep was reduced in anovulatory women. The analysis of associated variables of the inflammatory profile demonstrated that mean SpO2 during sleep was a predictive factor of IL-6 levels. CONCLUSIONS: Our data suggest that in premenopausal women with anovulation, a proinflammatory condition mediated by IL-6 is associated with lower oxygen levels during sleep. These findings reflect the balance between gynecological status, the immune system, and sleep, pointing to the need to control for these factors in clinical practice and research contexts.

Revisión de los criterios diagnósticos para el síndrome de ovario poliquístico / Review of diagnostic criteria for polycystic ovary syndrome

Resumen El síndrome de ovario poliquístico, es la alteración endocrina metabólica más frecuente en mujeres en edad fértil, teniendo implicaciones a nivel reproductivo, metabólico, cardiovascular y psicosocial. Actualmente, su sobrediagnóstico corresponde a una problemática común derivada de la heterogeneidad en la aplicación de los criterios actualmente avalados para su hallazgo, lo que ha contribuido en el incremento de tratamientos innecesarios, así como los efectos negativos en la calidad de vida y el bienestar de las pacientes falsamente calificadas con este trastorno. Se realizó una búsqueda en PubMed-MENDELEY y Ovid entre los meses de Febrero a Abril del 2020, obteniendo 43 artículos relacionados con el tema, publicados en los últimos 10 años. El conocimiento por parte del personal médico capacitado sobre los consensos actuales para la correcta evaluación del síndrome y el estudio individualizado de cada caso, corresponden las medidas más apropiadas para la reducción del sobrediagnóstico. MÉD.UIS.2020;33(3):21-28

Abstract Polycystic ovary syndrome is the most frequent metabolic endocrine disorder in women of childbearing age, having implications at both the reproductive, metabolic, cardiovascular and psychosocial levels. Currently, its overdiagnosis corresponds to a common problem derived from the heterogeneity in the application of the criteria currently endorsed for its discovery, which has contributed to the increase in unnecessary treatments, as well as the negative effects on the quality of life and well-being of falsely rated patients with this disorder. A search was made in PubMed-MENDELEY and Ovid between the months of February to April of 2020, obtaining 43 articles related to the topic, published in the last 10 years. The knowledge on the part of the trained medical personnel about the current consensuses for the correct evaluation of the syndrome and the individualized study of each case, correspond to the most appropriate measures for the reduction of this event. MÉD.UIS.2020;33(3):21-28

Association of obesity and anovulatory infertility.

OBJECTIVE: To verify the association of obesity and infertility related to anovulatory issues. METHODS: This case-control study was carried out with 52 women, aged 20 to 38 years, divided into two groups (infertile - cases - and fertile - control), seen at outpatient clinics, in the period from April to December, 2017. RESULTS: We found significant evidence that obesity negatively affects women's fertility (p=0.017). The group of infertile women was 7.5-fold more likely to be obese than fertile women. CONCLUSION: Strategies that encourage weight control are indicated for women with chronic anovulation, due to hight metabolic activity of adipose tissue.

Association of obesity and anovulatory infertility / Associação entre obesidade e infertilidade anovulatória

ABSTRACT Objective To verify the association of obesity and infertility related to anovulatory issues. Methods This case-control study was carried out with 52 women, aged 20 to 38 years, divided into two groups (infertile − cases − and fertile − control), seen at outpatient clinics, in the period from April to December, 2017. Results We found significant evidence that obesity negatively affects women's fertility (p=0.017). The group of infertile women was 7.5-fold more likely to be obese than fertile women. Conclusion Strategies that encourage weight control are indicated for women with chronic anovulation, due to hight metabolic activity of adipose tissue.

RESUMO Objetivo Verificar em mulheres a associação entre obesidade e infertilidade relacionada a questões anovulatórias. Métodos Estudo de caso-controle com 52 mulheres, de 20 a 38 anos, divididas em dois grupos (mulheres inférteis − casos − e férteis − controles), atendidas em ambulatórios, no período de abril a dezembro de 2017. Resultados Verificou-se evidência significativa de que a obesidade afeta negativamente na fertilidade das mulheres (p=0,017). O grupo de mulheres inférteis teve 7,5 vezes mais chances de serem obesas quando comparadas às mulheres férteis. Conclusão Estratégias que estimulem o controle do peso são indicadas para mulheres com anovulação crônica devido à elevada atividade metabólica do tecido adiposo.

Síndrome dos ovários policísticos: particularidades no manejo da infertilidade / Polycystic ovary syndrome: particularities in the management of infertility

A síndrome dos ovários policísticos (SOP) é responsável por cerca de 80% dos casos de infertilidade anovulatória. Não há na literatura evidências suficientes para a definição do tratamento ideal da infertilidade na SOP, mas repete-se que deve ser iniciado por mudanças no estilo de vida, e frequentemente envolve a indução farmacológica da ovulação e, em casos selecionados, as técnicas de reprodução assistida e o drilling ovariano laparoscópico. Este texto pretende reunir informações atuais sobre o manejo da infertilidade em mulheres com SOP e, dessa forma, permitir ao ginecologista a escolha da melhor abordagem, de forma Individualizada e baseada nas melhores evidências disponíveis.(AU)

Extensive management conditions do not modify the frequency of short ovulatory cycles in progesterone-treated does exposed to sexually active males.

Most goats exposed to males in confined conditions have short ovulatory cycles. The frequency of these cycles can be reduced with a progesterone treatment prior to the introduction of males. The objective of this study was to determine whether extensive management conditions modify the frequency of short ovulatory cycles in progesterone-treated does exposed to photostimulated males. One group of does remained in extensive management conditions and grazed daily from 10:00 to 18:00 h; two other groups were confined separately in shaded pens, and fed alfalfa hay. In March, females from the grazing group (n = 45; grazing-P4 group) and those from one confined group (n = 45; confined-P4 group) were treated with 25 mg of progesterone by intra-muscular injections 48 h before joining with photostimulated males (n = 3 per group). The other confined group did not receive the progesterone treatment and was exposed to two photostimulated males (n = 25; confined-control group). Does were exposed to males for 45 consecutive days. Determination of whether ovulations occurre were made by quantifying plasma progesterone concentrations after introduction of males. The proportion of does that had ovulations at least once was not different between groups (≥98%; P > 0.05). The proportion of does that had short ovulatory cycles differed between groups (P < 0.001), and this proportion was greater in the confined-control group (76%) than in confined-P4 (27%) and grazing-P4 groups (25%; P < 0.001). It is concluded that extensive management conditions do not modify the frequency of short ovulatory cycles in progesterone-treated does exposed to the photostimulated males.

C-type natriuretic peptide: a link between hyperandrogenism and anovulation in a mouse model of polycystic ovary syndrome.

The polycystic ovary (PCO) syndrome (PCOS) is the most common cause of anovulatory infertility in women and is associated with several clinical disorders. Despite the great amount of research in the area, mechanisms involved in the genesis of this syndrome remain poorly understood. In a recent issue of Clinical Science (vol. 132, issue 7, 759-776), Wang and colleagues, highlight the important role of overactivated C-type natriuretic peptide (CNP) and natriuretic peptide receptor 2 (CNP/NPR2) system in preventing oocyte maturation and ovulation in PCOS mice model induced by androgen. Dehydroepiandrosterone (DHEA) treatment caused anovulation, high levels of androgen and estrogen receptors (AR and ER) in the ovary, high expression of CNP and natriuretic peptide receptor 2 (NPR2) in granulosa cells (GC), and an increase in testosterone and estradiol (E2) levels in sera. The high level of CNP/NPR2 was associated with oocyte meiotic arrest and very low ovulation rate. Treatment with human chorionic gonadotropin (hCG) or inhibitors of AR or ER reduced the level of CNP/NPR2, which resulted in meiotic resumption and ovulation. The article provided important information for understanding the effect of ovarian steroids on control of oocyte maturation and fertility and highlighted CNP/NPR2 as a specific pathway that is potentially involved in the ovulatory disruption in PCOS.

Síndrome de Ovarios Poliquísticos / Polycystic ovary syndrome

Resumen El síndrome de ovarios poliquísticos (SOPQ) es la disfunción endocrino- metabólica más frecuente en mujeres de edad reproductiva. El diagnostico de esta patología se basa en la presencia de anovulación, hiperandrogenismo y ovarios poliquísticos. La etiología del SOPQ es compleja y multifactorial; por lo cual el tratamiento se basa en tratar las manifestaciones clínicas y la inducción de la ovulación en el momento que se desee la concepción.

Abstract Polycystic ovary syndrome is the most common endocrinologic and metabolic disfunction in reproductive- aged women. The diagnosis of this pathology is based on the presence of ovulatory dysfunction, hyperandrogenism and polycystic ovaries. Its ethiology is complex and with multiple factors, therefore its treatment is based on fixing the clinical manifestations of the syndrome and in the case of women who would like to conceive, in inducing ovulation.

Altered expression of IL-1ß, IL-1RI, IL-1RII, IL-1RA and IL-4 could contribute to anovulation and follicular persistence in cattle.

Cystic ovarian disease (COD) is an important cause of infertility in dairy cattle. The main signs of this infertility are ovulation failure and follicular persistence. The aim of this study was to examine the expression of the cytokines IL-1ß, IL-1RI, IL-1RII, IL-1RA and IL-4 in ovarian follicular structures at different times of persistence in a model of follicular persistence induced by prolonged administration of progesterone in dairy cows. Protein expression of IL-1ß, IL-1RI, IL-1RII, IL-1RA and IL-4 was evaluated by immunohistochemistry. Additionally, IL-1ß and IL-4 concentrations in follicular fluid and serum were determined by ELISA. In granulosa cells, IL1-RII and IL-4 expression was higher in follicles with different persistence times than in the control dominant follicles. IL-1RA expression was higher in persistent follicles of the P15 group (15 days of follicular persistence) than in those of the control group. In theca cells, IL-1RII expression was higher in persistent follicles of the P0 group (expected time of ovulation) than in dominant follicles from the control group (p < .05) and the other persistence groups, whereas IL-4 expression was higher in persistent follicles of groups P0 and P15 than in the dominant follicles of the control group (p < .05). Differences between serum and follicular fluid within each group were detected only in P0 for IL-1ß, and in the control, P10 and P15 groups for IL-4 (p < .05). These results complement previous results, evidencing that early development of COD in cows is concurrent with an altered expression of cytokines in different ovarian follicular structures and may contribute to the follicular persistence and ovulation failure found in cattle with follicular cysts.

Investigando a associação da obesidade com a infertilidade / Investigating the association between obesity and infertility

OBJETIVO: verificar a associação da obesidade com a infertilidade, destacando as questões anovulatórias. MÉTODO: Estudo de caso-controle com 52 mulheres , divididas nos grupos de mulheres inférteis (casos) e férteis (controles), atendidas em ambulatórios do IFF/FIOCRUZ. A análise utilizada foi a não-paramétrica e o método, equivalente a um teste-t independente, paramétrico denominado Mann-Whitney, efetuada no software Statistical Package for the Social Sciences (SPSS) da IBM. RESULTADOS: Há evidência significativa de que a obesidade interfere negativamente na fertilidade das mulheres. Observou-se um perfil com obesidade bem maior no grupo das pacientes inférteis do que no grupo das pacientes férteis, com valores de 50% e 18%, respectivamente. CONCLUSÃO: Adequações no hábito alimentar e na prática de atividade física são fatores importantes para promover mudanças na composição corporal e no estado nutricional, aumentando as chances das mulheres subférteis de reverterem a situação de infertilidade e terem uma gravidez saudável, diminuindo os gastos públicos gerados pelos tratamentos de infertilidade.

OBJECTIVE: to verify the association of obesity with infertility, highlighting the anovulatory issues. METHODS: Case-control study with 52 women divided into infertile (cases) and fertile (controls) women groups attended at IFF/FIOCRUZ outpatient clinics. The analysis used was the non-parametric and the method, equivalent to a parametric independent t-test called Mann-Whitney, performed in IBM's Statistical Package for the Social Sciences (SPSS) software. RESULTS: There is significant evidence that obesity negatively affects women's fertility. A much higher obesity profile was observed in the group of infertile patients than in the group of fertile patients, with values of 50% and 18%, respectively. CONCLUSION: Adequate dietary habits and practice of physical activity are important factors to promote changes in body composition and nutritional status, increasing the chances of subfertile women reversing their infertility status and having a healthy pregnancy by reducing public spending generated by infertility treatments.

Metformina en mujeres con síndrome de ovarios poliquísticos resistentes al citrato de clomifeno / Metformin in women with polycystic ovary syndrome resistant to clomiphene citrate

El objetivo de la investigación fue determinar la utilidad del uso de metformina en mujeres con síndrome de ovarios poliquísticos resistentes al citrato de clomífero. Esta investigación se realizó en el Hospital Central Dr. Urquinaona, Maracaibo, Venezuela, en el periodo de junio del 2012 a julio del 2017. Se incluyeron mujeres con infertilidad primaria por anovulación debido a síndrome de ovarios poliquísticos resistente a citrato de clomifeno. Las pacientes fueron elegidas al azar para ser asignadas al grupo A (casos ­ metformina) o grupo B (controles ­ placebo). Se analizaron las características generales, tasa de ovulación y de embarazo en las pacientes de cada uno de los grupos. Se seleccionaron 90 pacientes, las cuales fueron asignadas al grupo A (n = 45) o aquellas pacientes asignadas al grupo B (n = 45. No se observaron diferencias estadísticamente significativas entre los grupos con respecto a edad, índice de masa corporal, duración de la infertilidad y concentraciones de hormonales (p = ns). En el grupo A se observó que 62,2 % de las pacientes presentó ovulación comparado con 35,5 % en el grupo B (p = 0,0199). Por otra parte, 46,6 % de las pacientes del grupo A quedó embarazada comparado con 20,0 % en las pacientes del grupo B (p = 0,0132). Se concluye que el uso de metformina es útil en mujeres con síndrome de ovarios poliquísticos resistentes al citrato de clomifeno, ya que aumenta la tasa de ovulación y embarazo en este grupo de pacientes.

The aim of the research was to determine the usefulness of metformin in women with polycystic ovary syndrome resistant to clomiphene citrate. This research was conducted at the Hospital Central Dr. Urquinaona, Maracaibo, Venezuela, from June 2012 to July 2017. Women with primary infertility due to anovulation by polycystic ovary syndrome resistant to clomiphene citrate were included. Patients were randomized to be assigned with group A (cases - metformin) or group B (controls - placebo). General characteristics, ovulation rate and pregnancy in the patients of each of the groups were analyzed. A total of 90 patients were assigned to group A (n = 45) or patients assigned to group B (n = 45). There were no statistically significant differences between groups with respect to age, body mass index, duration of infertility and hormonal concentrations (p = ns). In group A, 62,2 % of the patients presented ovulation compared to 35,5 % in group B (p = 0.0199). On the other hand, 46,6 % of patients in group A became pregnant compared to 20.0% in patients in group B (p = 0.0132). It is concluded that treatment with metformin is useful in women with clomiphene citrate-resistant polycystic ovary syndrome since it increases the rate of ovulation and pregnancy in this group of patients.

Identification of differentially expressed genes in pathways of cerebral neurotransmission of anovulatory mice.

Polycystic ovary syndrome is the classic example of loss of functional cyclicity and anomalous feedback. In this case, the excessive extra-glandular production and conversion of androgens to estrogens are the pathophysiological basis of the chronic anovulation. The literature describes an experimental model of the polymicrocystic ovary in obese diabetic mice with insulin resistance. The fact that these animals exhibit obesity, insulin resistance, and infertility demonstrates their skill as an experimental model for polycystic ovary. A recent study using long protocol for up to 40 weeks showed that anovulatory and obese mice transplanted with adipose tissue from animals with normal weight have multiple changes in their phenotype. These changes include reduction of body weight, prevention of obesity, insulin level normalization, and insulin tolerance tests, preventing the elevation of steroids and especially the reversal of fertility restoration with anovulation. Considering that there are close relationships between the ovulation process and the central nervous system, we propose to evaluate the gene expression levels of 84 different genes involved in neurotransmission and insulin pathways in addition to examining the neurolipidosis differential murine brain before and after reversal of anovulation. The present study showed changes in gene expression of molecular markers in brain tissue of animals for brain neurotransmission pathways as well as pathways for insulin. GABAergic genes, muscarinic, serotonin receptors, receptor tyrosine kinase, and genes of interleukin 6 showed overexpression profile. There was also a change in the lipid content in anovulatory brain, obesity, and insulin resistant mice (Ob-/Ob-) compared with controls. The re-introduction of leptin in these animals appears to reverse, at least in part, this profile.