Pathophysiological and molecular considerations of viral and bacterial infections during maternal-fetal and –neonatal interactions of SARS-CoV-2, Zika, and Mycoplasma infectious diseases

During pregnancy, a series of physiological changes are determined at the molecular, cellular and macroscopic level that make the mother and fetus more susceptible to certain viral and bacterial infections, especially the infections in this and the companion review. Particular situations increase susceptibility to infection in neonates. The enhanced susceptibility to certain infections increases the risk of developing particular diseases that can progress to become morbidly severe. For example, during the current pandemic caused by the SARS-CoV-2 virus, epidemiological studies have established that pregnant women with COVID-19 disease are more likely to be hospitalized. However, the risk for intensive care unit admission and mechanical ventilation is not increased compared with nonpregnant women. Although much remains unknown with this particular infection, the elevated risk of progression during pregnancy towards more severe manifestations of COVID-19 disease is not associated with an increased risk of death. In addition, the epidemiological data available in neonates suggest that their risk of acquiring COVID-19 is low compared with infants (<12 months of age). However, they might be at higher risk for progression to severe COVID-19 disease compared with older children. The data on clinical presentation and disease severity among neonates are limited and based on case reports and small case series. It is well documented the importance of the Zika virus infection as the main cause of several congenital anomalies and birth defects such as microcephaly, and also adverse pregnancy outcomes. Mycoplasma infections also increase adverse pregnancy outcomes. This review will focus on the molecular, pathophysiological and biophysical characteristics of the mother/placental-fetal/neonatal interactions and the possible mechanisms of these pathogens (SARS-CoV-2, ZIKV, and Mycoplasmas) for promoting disease at this level. Abbreviations: ACE2, Angiotensin-converting enzyme 2 receptors; AF, Amniotic Fluid; Ang 1-7, Angiotensin 1-7; APTT, Activated partial thromboplastin time; ARDS, Acute respiratory distress syndrome; AT1R, Angiotensine type 1 receptor; B/L7, Cathepsin B/L7; BV, Bacterial Vaginitis; CDC, Centers for Disease Control and Prevention, USA; CMV, Cytomegalovirus; COVID-19, Coronavirus disease 2019; CoVs, Coronaviruses; CS, Cytokine Storm; CSF, Cerebrospinal Fluid; DIC, Disseminated Intravascular Coagulation; FRC, Functional residual capacity; GFR, Glomerular filtration rate; HIV, Human Immunodeficiency Virus; HSV, Herpes Simplex Virus; ILs, Interleukins; MAS, Macrophage Activation Syndrome; MasR, Mas Receptor (for Angiotensin 1-7); MIPL, Medically Induced Premature Labor; NK, Natural Killer; NGS, Next-Generation Sequencing; NF-κB, Nuclear factor kappa-light-chain-enhancer of activated B cells; PRMBL, Premature Rupture of Membranes Before Labor; RAS, Renin–angiotensin–aldosterone system; S, Spike Protein; SPL, Spontaneous Premature Labor; SVR, Systemic vascular resistance; TMPRSS2, Type II transmembrane serine protease; TORCH, Toxoplasmosis, Rubella, Cytomegalovirus and Herpes Virus-like infections; TNF-α, Tumor necrosis factor-α; WHO, World Health Organization; ZIKV, Zika Viru

Polycystic ovary syndrome and fetal programming

Cecilia Alonso: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República, Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Carolina Aristarán: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República, Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Esthefani Ávila: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República, Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Virginia Bermolen: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República, Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Ana Tihista: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República, Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Gabriel Anesetti: Docente supervisor. Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. Contacto: Gabriel Anesetti. Departamento de Histología y Embriología, Facultad de Medicina, Gral. Flores 2125, CP 11800, Montevideo, Uruguay. Tel: (598) 29243414 ext. 3481. E-mail: [email protected] síndrome de ovario poliquístico es un trastorno frecuente en las mujeres en edad reproductiva. En su patogenia influyen factores genéticos y ambientales. El hiperandrogenismo durante la vida fetal es el que se ha visto más vinculado a su desarrollo. En animales de experimentación se induce un síndrome similar, desarrollando un ambiente hiperandrogénico durante la gestación que conduce a una programación fetal. En estos modelos se vio que la exposición a un exceso de andrógenos durante la gestación determina en la descendencia femenina características similares a las encontradas en mujeres con síndrome de ovario poliquístico; como subfertilidad, alteraciones en el ciclo reproductivo, ovarios poliquísticos, alteraciones en el perfil lipídico y en la homeostasis insulina-glucosa, que difieren según el tiempo de exposición a andrógenos y la etapa de la gestación en la que ésta ocurre. Los factores genéticos juegan un rol importante en el desarrollo del síndrome de ovario poliquístico. Los que se han vinculado con más fuerza son aquellos que influyen en el sistema endócrino, como los relacionados con la secreción y acción de la insulina, de gonadotrofinas y andrógenos. Los factores inmunológicos también juegan un papel importante, entre éstos se pueden destacar los mediadores inflamatorios. Es necesario realizar más investigaciones para determinar si existen factores sobre los cuales se pueda actuar, además de tratamientos exitosos, para disminuir el hiperandrogenismo durante la gestación y de esta forma disminuir la incidencia del síndrome y sus repercusiones.Polycystic ovary syndrome is a common disorder in women of reproductive age. Its pathogenesis is influenced by genetic and environmental factors. Hyperandrogenism during fetal life has been closely linked to its development. A similar syndrome has been induced in research animals, developing an hyperandrogenic envi ronment during pregnancy leading to a fetal programming. Results show that exposure to androgen excess during pregnancy determined in female offspring characteristics such as subfertility, alterations in the reproductive cycle, polycystic ovaries, abnormal lipid profile and insulin-glucose homeostasis, similar to those found in women with polycystic ovary syndrome. These differ depending on the time of exposure and the stage of gestation when it occurs. Genetics plays an important role in the development of polycystic ovary syndrome. Genetic factors which have been linked more strongly are the ones that affect the endocrine system, such as those related to the secretion and action of insulin, gonadotrophins and androgens. Immunological factors also play an important role; among them, inflammatory mediators can be highlighted. Further research is necessary to determine whether there are factors over which it can be acted to re duce hyperandrogenism during pregnancy in order to decrease the incidence and impact of polycystic ovary syndrome, as well as successful treatments

Pathophysiological and molecular considerations of viral and bacterial infections during maternal-fetal and -neonatal interactions of SARS-CoV-2, Zika, and Mycoplasma infectious diseases

During pregnancy, a series of physiological changes are determined at the molecular, cellular and macroscopic level that make the mother and fetus more susceptible to certain viral and bacterial infections, especially the infections in this and the companion review. Particular situations increase susceptibility to infection in neonates. The enhanced susceptibility to certain infections increases the risk of developing particular diseases that can progress to become morbidly severe. For example, during the current pandemic caused by the SARS-CoV-2 virus, epidemiological studies have established that pregnant women with COVID-19 disease are more likely to be hospitalized. However, the risk for intensive care unit admission and mechanical ventilation is not increased compared with nonpregnant women. Although much remains unknown with this particular infection, the elevated risk of progression during pregnancy towards more severe manifestations of COVID-19 disease is not associated with an increased risk of death. In addition, the epidemiological data available in neonates suggest that their risk of acquiring COVID-19 is low compared with infants

Síndrome de ovario poliquístico y programación fetal

Polycystic ovary syndrome is a common disorder in women of reproductive age. Its pathogenesis is influenced by genetic and environmental factors. Hyperandrogenism during fetal life has been closely linked to its development. A similar syndrome has been induced in research animals, developing an hyperandrogenic environment during pregnancy leading to a fetal programming. Results show that exposure to androgen excess during pregnancy determined in female offspring characteristics such as subfertility, alterations in the reproductive cycle, polycystic ovaries, abnormal lipid profile and insulin-glucose homeostasis, similar to those found in women with polycystic ovary syndrome. These differ depending on the time of exposure and the stage of gestation when it occurs. Genetics plays an important role in the development of polycystic ovary syndrome. Genetic factors which have been linked more strongly are the ones that affect the endocrine system, such as those related to the secretion and action of insulin, gonadotrophins and androgens. Immunological factors also play an important role; among them, inflammatory mediators can be highlighted. Further research is necessary to determine whether there are factors over which it can be acted to reduce hyperandrogenism during pregnancy in order to decrease the incidence and impact of polycystic ovary syndrome, as well as successful treatments