Pathophysiology of polycystic ovary syndrome revisited: Current understanding and perspectives regarding future research.

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women and has lifelong effects on health. Methods: In this review, I discuss the pathophysiology of PCOS. First, I summarize our current understanding of the etiology and pathology of PCOS, then, discuss details of two representative environmental factors involved in the pathogenesis of PCOS. Finally, I present perspectives regarding the directions of future research. Main findings: The pathophysiology of PCOS is heterogeneous and shaped by the interaction of reproductive dysfunction and metabolic disorders. Hyperandrogenism and insulin resistance exacerbate one another during the development of PCOS, which is also affected by dysfunction of the hypothalamus-pituitary-ovarian axis. PCOS is a highly heritable disorder, and exposure to certain environmental factors causes individuals with predisposing genetic factors to develop PCOS. The environmental factors that drive the development of PCOS pathophysiology make a larger contribution than the genetic factors, and may include the intrauterine environment during the prenatal period, the follicular microenvironment, and lifestyle after birth. Conclusion: On the basis of this current understanding, three areas are proposed to be subjects for future research, with the ultimate goals of developing therapeutic and preventive strategies and providing appropriate lifelong management, including preconception care.

Factores de riesgos heredofamiliares, prenatales y perinatales en niños cubanos con autismo primario / Family inherited, prenatal and perinatal risk factors in Cuban children with primary autism

Introducción: El autismo primario es una heterogénea alteración neuroconductual, de causa no precisa, en la que tanto los genes como el ambiente contribuyen a la patogenia del trastorno. Objetivo: Identificar factores de riesgos heredofamiliares, prenatales y perinatales en niños cubanos con autismo primario. Material y Métodos: Se realizó una investigación observacional tipo casos y controles (1:1) en niños con autismo primario, atendidos en el Hospital Pediátrico "Juan Manuel Márquez", La Habana; en el período de octubre de 2014 a septiembre de 2019. La muestra quedó conformada por 126 casos y 126 controles. Se recolectaron los datos sobre la historia de enfermedades neuropsiquiátricas de tres generaciones, antecedentes prenatales y perinatales. Se realizó una regresión logística multivariada para identificar factores de riesgos relacionados con el autismo primario. Resultados: El odds de presentar autismo primario fue aproximadamente siete y cuatro veces superior en hijos de madres y padres con edad avanzada, respectivamente. Los antecedentes de trastornos del lenguaje y epilepsia en familiares de primer grado, confirió un odds de presentar autismo 27 y 24 veces mayor, respectivamente. El odds de presentar autismo fue aproximadamente diez veces mayor en los hijos de gestantes con anemia, ocho veces en hijos de gestantes que tuvieron gestorragias y 18 veces para los nacidos de madres con antecedentes de diabetes mellitus pregestacional. Conclusiones: Los antecedentes de enfermedades heredofamiliares neuropsiquiátricas y de factores ambientales prenatales y perinatales relacionados con eventos hipoxémicos constituyen factores de riesgo para el autismo primario en la muestra de niños cubanos estudiados(AU)

Introduction: Primary autism is a heterogeneous neurobehavioral disorder of uncertain etiology in which both genes and the environment contribute to the pathogenesis of the disorder. Objective: To identify family inherited, prenatal and perinatal risk factors in Cuban children with primary autism. Material and Methods: An observational case-control study (1:1) was carried out in children with primary autism, treated at "Juan Manuel Márquez" Pediatric Hospital, Havana, in the period from October of 2014 to September of 2019. The sample was made up of 126 cases and 126 controls. Data on neuropsychiatric diseases, prenatal and perinatal history of three generations were collected. Multivariate logistic regression was performed to identify risk factors related to primary autism. Results: The odds of presenting primary autism were approximately seven and four times higher in children of mothers and fathers of advanced ages, respectively. A history of language disorders and epilepsy in first-degree relatives conferred 27- and 24-fold higher odds of presenting with autism, respectively. The odds of presenting autism were approximately ten times greater in children born to pregnant women with anemia, eight times in children born to pregnant women who had bleeding during pregnancy, and 18 times in those born to mothers with a history of pregestational diabetes mellitus. Conclusions: The history of inherited neuropsychiatric diseases and prenatal and perinatal environmental factors related to hypoxemic events are risk factors for primary autism in the sample of Cuban children studied(AU)

Temporal relationship between alterations in the gut microbiome and the development of polycystic ovary syndrome-like phenotypes in prenatally androgenized female mice.

It has been recently recognized that prenatal androgen exposure is involved in the development of polycystic ovary syndrome (PCOS) in adulthood. In addition, the gut microbiome in adult patients and rodents with PCOS differs from that of healthy individuals. Moreover, recent studies have suggested that the gut microbiome may play a causative role in the pathogenesis of PCOS. We wondered whether prenatal androgen exposure induces gut microbial dysbiosis early in life and is associated with the development of PCOS in later life. To test this hypothesis, we studied the development of PCOS-like phenotypes in prenatally androgenized (PNA) female mice and compared the gut microbiome of PNA and control offspring from 4 to 16 weeks of age. PNA offspring showed a reproductive phenotype from 6 weeks and a metabolic phenotype from 12 weeks of age. The α-diversity of the gut microbiome of the PNA group was higher at 8 weeks and lower at 12 and 16 weeks of age, and the ß-diversity differed from control at 8 weeks. However, a significant difference in the composition of gut microbiome between the PNA and control groups was already apparent at 4 weeks. Allobaculum and Roseburia were less abundant in PNA offspring, and may therefore be targets for future interventional studies. In conclusion, abnormalities in the gut microbiome appear as early as or even before PCOS-like phenotypes develop in PNA mice. Thus, the gut microbiome in early life is a potential target for the prevention of PCOS in later life.