Physiological and Pathophysiological Role of Large-Conductance Calcium-Activated Potassium Channels (BKCa) in HUVECs and Placenta.

BKCa channels (large-conductance Ca2+-activated K+ channels) play a critical role in regulating vascular tone and blood pressure. These channels are present in the smooth muscle cells of blood vessels and are activated by voltage and increased intracellular Ca2+ concentration. More recently, the expression and activity of BKCa have been proposed to be relevant in endothelial cells, too, specifically in human umbilical vein endothelial cells (HUVECs), the more studied cell type in the fetoplacental circulation. The role of BKCa in endothelial cells is not well understood, but in HUVECs or placental endothelium, these channels could be crucial for vascular tone regulation during pregnancy as part of endothelium-derived hyperpolarization (EDH), a key mechanism for an organ that lacks nervous system innervation like the placenta.In this review, we will discuss the evidence about the role of BKCa (and other Ca2+-activated K+ channels) in HUVECs and the placenta to propose a physiological mechanism for fetoplacental vascular regulation and a pathophysiological role of BKCa, mainly associated with pregnancy pathologies that present maternal hypertension and/or placental hypoxia, like preeclampsia.

Pathophysiology of Preeclampsia and L-Arginine/L-Citrulline Supplementation as a Potential Strategy to Improve Birth Outcomes.

In preeclampsia, the shallow invasion of cytotrophoblast cells to uterine spiral arteries, leading to a reduction in placental blood flow, is associated with an imbalance of proangiogenic/antiangiogenic factors to impaired nitric oxide (NO) production. Proangiogenic factors, such as vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), require NO to induce angiogenesis through antioxidant regulation mechanisms. At the same time, there are increases in antiangiogenic factors in preeclampsia, such as soluble fms-like tyrosine kinase type 1 receptor (sFIt1) and toll-like receptor 9 (TLR9), which are mechanism derivates in the reduction of NO bioavailability and oxidative stress in placenta.Different strategies have been proposed to prevent or alleviate the detrimental effects of preeclampsia. However, the only intervention to avoid the severe consequences of the disease is the interruption of pregnancy. In this scenario, different approaches have been analysed to treat preeclamptic pregnant women safely. The supplementation with amino acids is one of them, especially those associated with NO synthesis. In this review, we discuss emerging concepts in the pathogenesis of preeclampsia to highlight L-arginine and L-citrulline supplementation as potential strategies to improve birth outcomes. Clinical and experimental data concerning L-arginine and L-citrulline supplementation have shown benefits in improving NO availability in the placenta and uterine-placental circulation, prolonging pregnancy in patients with gestational hypertension and decreasing maternal blood pressure.

Development of the Placenta and Brain Are Affected by Selective Serotonin Reuptake Inhibitor Exposure During Critical Periods.

Selective serotonin reuptake inhibitors (SSRIs) are usually prescribed to treat major depression and anxiety disorders. Fetal brain development exhibits dependency on serotonin (5-hydroxytryptamine, 5-HT) from maternal, placental, and fetal brain sources. At very early fetal stages, fetal serotonin is provided by maternal and placental sources. However, in later fetal stages, brain sources are indispensable for the appropriate development of neural circuitry and the rise of emergent functions implied in behavior acquisition. Thus, susceptible serotonin-related critical periods are recognized, involving the early maternal and placental 5-HT synthesis and the later endogenous 5-HT synthesis in the fetal brain. Acute and chronic exposure to SSRIs during these critical periods may result in short- and long-term placental and brain dysfunctions affecting intrauterine and postnatal life. Maternal and fetal cells express serotonin receptors which make them susceptible to changes in serotonin levels influenced by SSRIs. SSRIs block the serotonin transporter (SERT), which is required for 5-HT reuptake from the synaptic cleft into the presynaptic neuron. Chronic SSRI administration leads to pre- and postsynaptic 5-HT receptor rearrangement. In this review, we focus on the effects of SSRIs administered during critical periods upon placentation and brain development to be considered in evaluating the risk-safety balance in the clinical use of SSRIs.

Effects of Prenatal Cannabinoids Exposure upon Placenta and Development of Respiratory Neural Circuits.

Cannabis use has risen dangerously during pregnancy in the face of incipient therapeutic use and a growing perception of safety. The main psychoactive compound of the Cannabis sativa plant is the phytocannabinoid delta-9-tetrahydrocannabinol (A-9 THC), and its status as a teratogen is controversial. THC and its endogenous analogues, anandamide (AEA) and 2-AG, exert their actions through specific receptors (eCBr) that activate intracellular signaling pathways. CB1r and CB2r, also called classic cannabinoid receptors, together with their endogenous ligands and the enzymes that synthesize and degrade them, constitute the endocannabinoid system. This system is distributed ubiquitously in various central and peripheral tissues. Although the endocannabinoid system's most studied role is controlling the release of neurotransmitters in the central nervous system, the study of long-term exposure to cannabinoids on fetal development is not well known and is vital for understanding environmental or pathological embryo-fetal or postnatal conditions. Prenatal exposure to cannabinoids in animal models has induced changes in placental and embryo-fetal organs. Particularly, cannabinoids could influence both neural and nonneural tissues and induce embryo-fetal pathological conditions in critical processes such as neural respiratory control. This review aims at the acute and chronic effects of prenatal exposure to cannabinoids on placental function and the embryo-fetal neurodevelopment of the respiratory pattern. The information provided here will serve as a theoretical framework to critically evaluate the teratogen effects of the consumption of cannabis during pregnancy.

COVID-19 on Pregnancy Outcomes, Mental Health and Placenta: Focus in Latin America.

The COVID-19 pandemic has impacted many aspects of health and society worldwide. One vulnerable group that faced SARS-CoV-2 infection is pregnant women, who were considered to have potentiated risk factors. In physiological pregnancy, maternal systems have several changes and adaptations to support fetal development. These changes involve regulations of cardiovascular, respiratory, and immunologic systems, among others, which SARS-CoV-2 could severely alter. Furthermore, the systemic effects of viral infection could be associated with placental dysfunction and adverse pregnancy outcomes, which have been studied from the start of the pandemic to date. Additionally, pregnancy is a condition of more significant mental health vulnerability, especially when faced with highly stressful situations. In this chapter, we have collected information on the effect of COVID-19 on maternal mortality, the SARS-CoV-2 infection rate in pregnancy, and the impact on pregnancy outcomes, maternal mental health, and placental function, with a particular focus on studies that consider the Latin American population.

The Placental Function Beyond Pregnancy: Insights from Latin America.

Currently, more than 100,000 papers had been published studying the placenta in both physiological and pathological contexts. However, relevant health conditions affecting placental function, mostly found in low-income countries, should be evaluated deeper. This review will raise some - of what we think necessary - points of discussion regarding challenging topics not fully understood, including the paternal versus maternal contribution on placental genes imprinting, placenta-brain communication, and some environmental conditions affecting the placenta. The discussions are parts of an international effort to fulfil some gaps observed in this area, and Latin-American research groups currently evaluate that.

Flickering of fetal erythrocytes membrane under gestational diabetes observed with dual time resolved membrane fluctuation spectroscopy.

The membrane flickering of human fetal red blood cells (RBCs) affected by gestational diabetes mellitus (GDM) was studied with dual time resolved membrane fluctuation spectroscopy (D-TRMFS). This new technique is a modified version of the dual optical tweezers method that has been adapted to measure the mechanical properties of RBCs at two distant membrane points simultaneously. The micro-rheological parameters were obtained from direct membrane flickering measurements, followed by Fourier decomposition and cell membrane model adjustment. Our results show a significant decrease of 6.01 ± 1.19 nm in membrane fluctuations amplitude in healthy fetal, compared with healthy adult RBCs, meanwhile the amplitude in GDM cells increased 3.22 ± 1.10 nm compared with healthy fetal RBCs. Between GDM and healthy fetal RBCs, there are significant differences, especially in the bending modulus. Considering the mean of the two membrane points measured, the tension for GDM RBCs increased by 6.431 ± 3.57 (10-7 [N/m]) compared with healthy fetal RBCs, meanwhile, the bending was increased by 2.483 ± 0.58 (10-19 [J]) in GDM compared with healthy fetal RBCs. These results showed significant increment of 1.23 ± 0.07-fold and 3.29 ± 0.36-fold in tension and bending modulus in GDM, respectively. The strong impact of GDM on bending modulus could be associated with oxidative stress and lipid peroxidation, previously reported in fetal plasma of GDM cases.

Incidencia de diabetes gestacional en Chile durante el periodo 2001-2022

Introducción: La diabetes mellitus gestacional (DG) se define como una hiperglucemia que se diagnostica por primera vez durante la gestación. Objetivo: Describir la incidencia de diabetes gestacional (DG) durante el periodo 2001-2022 en Chile. Método: Estudio observacional, descriptivo, ecológico y longitudinal. Se incluyeron los egresos hospitalarios consignados como diabetes durante el embarazo y DG en el periodo 2001-2022, de la base de datos del Departamento de Estadística e Información en Salud. Se determinó la incidencia de DG por la cantidad de partos institucionalizados, para cada año. Se analizaron la tendencia en el periodo y las diferencias entre regiones. Resultados: Se determinó un aumento de 2,615 casos de DG por 1000 partos atendidos por año en el periodo 2001-2022. En particular, en el periodo 2016-2022 la incidencia aumentó hasta 6,746 casos de DG por 1000 partos por año. En el año 2022, la región de La Araucanía presentó una incidencia de 284,4 casos por 1000 partos, lo que representa un aumento del 503% en relación con la incidencia media nacional (56,5 casos por 1000 partos). Conclusiones: Se demuestra un aumento significativo de la DG, en especial desde 2016. La situación en La Araucanía podría relacionarse con los niveles de pobreza multidimensional.

Introduction: Gestational diabetes mellitus (GDM) is defined as hyperglycemia first diagnosed during pregnancy. Objetive: To describe the incidence of gestational diabetes (GD) during the period 2001-2022 in Chile. Method: Observational, descriptive, ecological, longitudinal study. Hospital records of diabetes during pregnancy and GD in the period 2001-2022 were included, from the database of the Department of Statistics and Health Information. The incidence of GD was determined by the number of births, for each year. Trends in the period and differences between regions were analysed. Results: The results show an increase of 2.615 GD cases per 1000 births per year in the period 2001-2022. Particularly, in the period 2016-2022 the incidence increased to 6.746 cases of GD per 1000 births per year. In 2022, La Araucanía region presented an incidence of 284.4 cases per 1000 births, which represents an increase of 503% in relation to the mean national incidence (56.5 cases per 1000 births). Conclusions: A significant increase in DG is demonstrated, especially since 2016. The situation in La Araucanía could be related to the levels of multidimensional poverty.

Tipos de partos y niveles de oxitocina, cortisol y hormonas tiroideas en plasma del cordón umbilical / Types of deliveries and levels of oxytocin, cortisol and thyroid hormones in umbilical cord plasma

Introducción: La placenta sintetiza y secreta varias hormonas que permiten la regulación del embarazo, el trabajo de parto y la adaptación metabólica materno-fetal. Su comportamiento asociado al tipo de parto puede dar información relevante sobre efectos epigenéticos. Objetivo: Describir el tipo de parto con los niveles de oxitocina, cortisol y hormonas tiroideas en plasma de cordón umbilical al nacer. Método: A 50 mujeres con embarazos principalmente normales se les cuantificaron los niveles neurohormonales en plasma de cordón umbilical, obtenido inmediatamente tras el periodo expulsivo. Los resultados se incorporaron a la base de datos clínicos de cada participante y se analizaron con Stata v.14.0. El protocolo fue aprobado por el comité de ética. Resultados: Hubo 33 partos vaginales (12 espontáneos, 13 acelerados y 8 inducidos) y 17 cesáreas (7 electivas y 10 de urgencia). Se observaron mayores niveles de cortisol en los partos vaginales acelerados; las cesáreas tuvieron menores niveles de cortisol y hormona estimulante de la tiroides. Las intervenciones clínicas, con altos o bajos niveles hormonales, están en directa relación con el tipo de parto. Conclusiones: El cortisol y la hormona estimulante de la tiroides medidos en plasma de cordón umbilical variaron según el tipo de parto. Esto es una primera cuantificación de hormonas en plasma de cordón umbilical y su posible regulación placentaria a propósito del tipo de parto.

Introduction: The placenta synthesizes and secretes several hormones allowing the regulation of pregnancy, labor and maternal-fetal metabolic adaptation. Their behavior associated with the type of delivery, may provide relevant information on epigenetic effects. Objective: To describe the type of delivery with the levels of oxytocin, cortisol and thyroid hormones in umbilical cord plasma at birth. Method: Neurohormonal levels from umbilical cord plasma obtained immediately post expulsion, were quantified in 50 women with mainly normal pregnancies. Results incorporated into the clinical database of each participant, statistically analyzed in Stata v.14.0. Protocol approved by ethics committee. Results: 33 were vaginal deliveries (12 spontaneous, 13 accelerated, 8 induced) and 17 cesarean sections (7 elective and 10 emergency). Higher cortisol levels were observed in accelerated vaginal deliveries, cesarean sections had lower cortisol and thyroid stimulating hormone levels. While clinical interventions, with high or low hormone levels, were related to the type of delivery. Conclusions: Cortisol and thyroid stimulating hormone measured in umbilical cord plasma varied according to the type of delivery. This is a first quantification of hormones in umbilical cord plasma and their possible placental regulation in relation to the type of delivery.