Excessive Pregestational Weight and Maternal Obstetric Complications: The Role of Adipokines.

There is a high frequency of overweight and obesity in women of reproductive age. Women who start pregnancy with overweight or obesity have an increased risk of developing maternal obstetric complications such as gestational hypertension, pre-eclampsia, gestational diabetes mellitus, postpartum hemorrhage, and requiring C-section to resolve the pregnancy with a higher risk of C-section surgical site infection. Excessive weight in pregnancy is characterized by dysregulation of adipokines, the functions of which partly explain the predisposition of pregnant women with overweight or obesity to these maternal obstetric complications. This review compiles, organizes, and analyzes the most recent studies on adipokines in pregnant women with excess weight and the potential pathophysiological mechanisms favoring the development of maternal pregnancy complications.

New Insights into Adipokines in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is the most common metabolic disorder of pregnancy and has considerable short- and long-term consequences for the health of both the mother and the newborn. Within its pathophysiology, genetic, nutritional, epigenetic, immunological, and hormonal components have been described. Within the last two items, it is known that different hormones and cytokines secreted by adipose tissue, known collectively as adipokines, are involved in the metabolic alterations underlying GDM. Although the maternal circulating profile of adipokines in GDM has been extensively studied, and there are excellent reviews on the subject, it is in recent years that more progress has been made in the study of their expression in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), placenta, and their concentrations in the umbilical circulation. Thus, this review compiles and organizes the most recent findings on the maternal and umbilical circulating profile and the levels of expression of adipokines in VAT, SAT, and placenta in GDM.

Epigenetic Alterations Related to Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is the most common metabolic complication in pregnancy, which affects the future health of both the mother and the newborn. Its pathophysiology involves nutritional, hormonal, immunological, genetic and epigenetic factors. Among the latter, it has been observed that alterations in DNA (deoxyribonucleic acid) methylation patterns and in the levels of certain micro RNAs, whether in placenta or adipose tissue, are related to well-known characteristics of the disease, such as hyperglycemia, insulin resistance, inflammation and excessive placental growth. Furthermore, epigenetic alterations of gestational diabetes mellitus are observable in maternal blood, although their pathophysiological roles are completely unknown. Despite this, it has not been possible to determine the causes of the epigenetic characteristics of GDM, highlighting the need for integral and longitudinal studies. Based on this, this article summarizes the most relevant and recent studies on epigenetic alterations in placenta, adipose tissue and maternal blood associated with GDM in order to provide the reader with a general overview of the subject and indicate future research topics.

Immune tolerance at the maternal-placental interface in healthy pregnancy and pre-eclampsia.

AIM: The objective of this review is to describe the immunological mechanisms which facilitate maternal tolerance at the maternal-placental interface, and to discuss how these mechanisms are disrupted in pre-eclampsia. METHODS: A literature review was performed based on the analysis of papers available on PubMed. The most important and relevant studies regarding the immunological mechanisms which facilitate maternal tolerance in healthy pregnancy and pre-eclampsia are presented in this article. RESULTS: The maternal-placental interface is the site where the immune tolerance begins and develops. Within the innate immunity, natural killer cells, macrophages and dendritic cells play a pivotal role in tolerance through regulation of inflammation. On the other hand, within the adaptive immunity, the correct increase of regulatory T cells is crucial for ensuring immune tolerance toward placental cells. Disturbances in maternal tolerance can lead to the appearance of pregnancy complications such as pre-eclampsia, which has a considerable impact on perinatal morbidity and mortality. CONCLUSION: Our partial knowledge of immunological mechanisms involved in tolerance at the maternal-placental interface indicates that pre-eclampsia is characterized by alterations of this maternal immune tolerance, which could represent the origin of the disease.

Placental Proinflammatory State and Maternal Endothelial Dysfunction in Preeclampsia.

OBJECTIVE: To evaluate the placental and decidual gene expression and maternal and umbilical serum concentrations of tumor necrosis factor alpha, interleukin 6 (IL-6), IL-8, IL-10, IL-1 receptor antagonist (IL-1RA), intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (VCAM-1), along with the proinflammatory/anti-inflammatory cytokine ratios in women with preeclampsia (PE) vs. women with normal pregnancy (NP), and to analyze PE classified as early- (EO) and late-onset (LO). METHODS: This cross-sectional study was performed with 50 women with PE (EO n = 30, LO n = 20) and 50 women with NP. Tissue gene expression levels were measured by real-time RT-PCR. Cytokines and adhesion molecules serum concentrations were measured by immunoassays. RESULTS: In PE, placental expression of IL-10 and IL-1RA was lower, while placental IL-8/IL-1RA ratio and maternal concentrations of VCAM-1 were higher vs. NP. In EO, placental expression of IL-10 was lower, while placental IL-8/IL-10 and IL-8/IL-1RA ratios were higher than LO and NP. Maternal concentrations of IL-6 were higher in LO than EO and NP. Throughout PE, maternal VCAM-1 concentrations were higher vs. NP. No significant differences were observed in the decidual expression and umbilical concentrations of the markers between the groups. CONCLUSION: PE associates with a proinflammatory placental state; however, EO associates with a proinflammatory placental state, while LO associates with systemic maternal inflammation. Both subtypes associated with maternal endothelial dysfunction.

[Clinical implications of basic research in preeclampsia: immunological tolerance]. / Implicaciones clínicas de la investigación básica de la preeclampsia: tolerancia inmunológica.

Preeclampsia is one of the main causes of maternal and perinatal mortality in the world; however, the pathophysiologic pathways haven't been clearly elucidated. It is thought to result from a breakdown of maternal tolerance to paternal antigens in placenta that start an immune response against the trophoblast inducing a defective placentation and a hipoxic/isquemic environment which in turn triggers a systemic inflamatory response. This review gives an overview of the mechanims involved in maternal tolerance, how these are disrupted in preeclampsia, and how they contribute to the inflamatory response.

Neuroprotection mediated by prolactin against streptozotocin injury in brain rat areas.

Prolactin has been recognized as neuroprotective hormone against various types of neuronal damage. This study was aimed to determine if prolactin protects against streptozotocin injury. A series of experiments were performed to determine neuronal survival by counting total neurons in medial hippocampus cortex and cerebellum. Astrogliosis was determined by immunofluorescence assays using GFAP, and behavioral improvement by prolactin after neuronal damage was determined by open-field and light-dark box tests. Results demonstrated that prolactin induced significant neuronal survival in both the hippocampus and cortex, but not in the cerebellum. No increase in astrogliosis was identified, but a significant reduction in anxiety levels was observed. Overall data indicate that prolactin may protect against a complex form of cell damage including oxidant stress and metabolic disruption by streptozotocin. Prolactin may be helpful strategy in the treatment of neuronal damage in neurological diseases.

Differential Expression of FXR and Genes Involved in Inflammation and lipid Metabolism Indicate Adipose Tissue Dysfunction in Gestational Diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most frequent metabolic alteration in pregnancy. Several abnormalities in visceral adipose tissue (VAT) have been described as part of its pathophysiology including hypertrophy, inflammation and altered lipid metabolism. Farnesoid X receptor (FXR) is involved in adipocyte physiology and inflammation, so its expression may correlate with the expression of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), lipoprotein lipase (LPL), and two fatty acid transporters (SLC27A2, and SLC27A4). AIM: To compare the FXR, LPL, SLC27A2, SLC27A4, TNF-α, and IL-10 mRNA expression in VAT between women with GDM and healthy pregnant (HP) women. Secondarily, to evaluate the potential correlation between these expression levels. MATERIALS AND METHODS: Cross-sectional study of 50 GDM and 50 HP women. Conventional biochemical tests were performed and relative mRNA expression in VAT was measured by RT-qPCR. RESULTS: Gene expression levels of FXR and IL-10 were lower, whereas those of LPL, as well as the TNF-α/IL-10 ratio, were higher in women with GDM compared to HP. Pre-pregnancy BMI was the main significant independent variable for FXR levels in VAT from women with GDM. In all women, LPL expression levels correlated positively with those of SLC27A2. Only in women with GDM, IL-10 expression levels correlated negatively with those of SLC27A2, and SLC27A4. CONCLUSIONS: GDM is associated with decreased expression of FXR and IL-10 and increased expression of LPL, as well as a higher TNF/IL-10 ratio in VAT. These results suggest increased lipid storage and pro-inflammatory state indicating VAT dysfunction in this metabolic disorder.

Gestational Weight Gain Is Associated with the Expression of Genes Involved in Inflammation in Maternal Visceral Adipose Tissue and Offspring Anthropometric Measures.

BACKGROUND: Adequate gestational weight gain (GWG) is essential for maternal and fetal health. GWG may be a sign of higher visceral adipose tissue (VAT) accretion. A higher proportion of VAT is associated with an inflammatory process that may play a role in the fetal programming of obesity. This study aimed to (1) compare the expression of genes involved in inflammatory responses (TLR2, TLR4, NFκB, IKKß, IL-1RA, IL-1ß, IL-6, IL-10, TNF-α) in the VAT of pregnant women according to GWG and (2) explore whether VAT inflammation and GWG are related to offspring anthropometric measures. MATERIAL AND METHODS: 50 women scheduled for cesarean section who delivered term infants were included in the study. We collected maternal omental VAT, and the expression of genes was examined with RT-qPCR. RESULTS: Women with excessive and with adequate GWG had significantly higher expressions of most inflammatory genes than women with insufficient GWG. Neonates from mothers with excessive GWG had greater birth weight and chest circumference than those from mothers with insufficient GWG. GWG was positively correlated with fetal birth weight. CONCLUSIONS: The VAT expression of most genes associated with inflammatory pathways was higher in excessive and adequate GWG than in pregnant women with insufficient GWG. Moreover, GWG was found to be positively associated with newborn weight.

Role of Oxidative Stress and Inflammation in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. It is related to several gestational and fetal adverse outcomes. Moreover, women with GDM and their infants have a high risk of developing type 2 diabetes in the future. The pathogenesis of GDM is not completely understood; nevertheless, two factors that contribute to its development are oxidative stress and inflammation. Oxidative stress and inflammation are related; reactive oxygen species (ROS) production can activate inflammatory cells and enhance the production of inflammatory mediators. Inflammation, in turn, leads to an increased ROS release, causing a vicious circle to ensue. Inflammatory responses can be achieved via the activation of the NF-κB signaling pathway. Herein, we review the English literature regarding oxidative stress and inflammation evaluated simultaneously in the same population, attempting to identify mechanisms through which these factors contribute to the development of GDM. Furthermore, the modulation of oxidative stress and inflammation by different therapies used in women with GDM and in cell models of GDM is included in the review. Probiotics and nutrient supplementations have been shown to reduce biomarkers of inflammation and oxidative stress in vitro and in women with GDM.

Hirsutism and Polycystic Ovarian Morphology are the Most Frequent Components of Polycystic Ovary Syndrome in Women with Type 1 Diabetes.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. In Mexico, its prevalence in patients with type 1 diabetes (T1D) is unknown. AIM: To evaluate the clinical and biochemical characteristics of patients with T1D with and without PCOS. METHODS: A cross-sectional study was conducted to evaluate women of reproductive age with T1D for the diagnosis of PCOS using the criteria of the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine. Clinical information was obtained from clinical records, and we recorded anthropometric variables and performed a laboratory test during the follicular phase. The estimated glucose disposal rate and visceral adiposity index were also calculated to assess insulin resistance. Subsequently, participants were evaluated based on the presence or absence of PCOS. RESULTS: Thirty-nine percent of patients with T1D had PCOS. The most frequent components of PCOS were polycystic ovary morphology (58.5%), clinical hyperandrogenism (41.5%), oligomenorrhea (29.2%), and biochemical hyperandrogenism (19.5%). Patients with PCOS used more insulin per day (1.04 ± 0.33 vs. 0.71 ± 0.29 IU/kg/d, p = 0.003), had lower fasting glucose (116.4 ± 59.79 vs. 161.16 ± 63.9 mg/dl, p = 0.029) and higher right ovarian volume (11.36 [8.64-15.89] vs. 6.9 [5.55-8.77] cm3, p = 0.005) and Ferriman-Gallwey scores (9.06 ± 2.05 vs. 7.12 ± 3.15 points, p = 0.035) compared to patients without PCOS. The frequency of insulin resistance and metabolic syndrome in women with PCOS was 37.5 and 18.8%, respectively. CONCLUSION: PCOS is a very heterogeneous entity, with a high frequency in women with T1D.

Coronavirus disease 2019 and pregnancy. / Enfermedad por coronavirus 2019 y embarazo.

Historically, viral respiratory infections in pregnant women have shown an increase in the risk of morbidity and mortality. With regards to COVID-19, information is limited and a greater risk of severe morbidity or mortality has not been shown, when compared to general population; however, pregnant women with comorbidities such as obesity, type 2 diabetes mellitus and hypertension have shown a greater severity of the disease, consistent with the general population with these comorbidities. The risk of vertical transmission appears to be low: it has not been demonstrated in any case during the current outbreak of COVID-19 in China, nor in previous epidemics of similar coronaviruses (SARS-CoV and MERS-CoV). Existing studies have not demonstrated the presence of the virus in genital fluid, amniotic fluid or maternal milk. Described cases of infection in newborns probably come from horizontal transmission, which suggests breastfeeding with respiratory hygiene measures. Given that COVID-19 is a new disease that has extended around the world and that current knowledge is still insufficient, it is mandatory the continued accumulation of data to discover in depth the action mechanisms of SARS-CoV-2 virus, responsible for the disease, and constant update of means of prevention and handling of the disease.

Históricamente, las infecciones respiratorias virales en mujeres embarazadas han mostrado un incremento en el riesgo de morbilidad y mortalidad. En relación con el COVID-19 la información es limitada y no ha mostrado un mayor riesgo de morbilidad severa o mortalidad en comparación con la población en general; sin embargo, las mujeres embarazadas con comorbilidades como obesidad, diabetes mellitus tipo 2 e hipertensión arterial han presentado una mayor severidad de la enfermedad de manera más consistente a lo que ocurre en la población general con esas comorbilidades. El riesgo de transmisión vertical parece bajo: no se ha podido demostrar en ningún caso durante el brote actual de COVID-19 en China, ni tampoco en epidemias previas por otros coronavirus similares (SARS-CoV y MERS-CoV). Los estudios existentes no han evidenciado presencia del virus en fluidos genitales, líquido amniótico, ni tampoco en la leche materna. Los casos descritos de infección en recién nacidos provienen probablemente de transmisión horizontal, por lo que se sugiere la lactancia materna con medidas de higiene respiratoria. Debido a que la enfermedad por coronavirus se ha extendido a nivel mundial y el conocimiento actual es aún insuficiente, es imperativo el cúmulo de evidencia y profundizar en los mecanismos de acción del virus SARS-CoV-2, responsable de la enfermedad, y también que se actualicen constantemente las medidas de prevención y manejo de la enfermedad.

Alteración del perfil materno de adipocinas circulantes en preeclampsia / Altered maternal adipokine profile in preeclampsia

Resumen OBJETIVOS: Evaluar las concentraciones séricas maternas de las adipocinas: adiponectina, adipsina, leptina, lipocalina-2, proteína quimioatrayente de monocitos-1, factor de crecimiento nervioso, resistina y factor de necrosis tumoral alfa y su relación con el índice de masa corporal previo al embarazo y la ganancia de peso gestacional en mujeres con preeclampsia comparadas con mujeres sanas, y hacer un análisis de la clasificación de preeclampsia en temprana y tardía. MATERIALES Y MÉTODOS: Estudio transversal, comparativo, retrolectivo, con muestreo no probabilístico por conveniencia efectuado en pacientes atendidas en el Hospital de Gineco-Obstetricia 3, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS). En el preoperatorio se tomó una muestra de sangre para determinar las concentraciones séricas de las adipocinas mediante ensayos multianalito. RESULTADOS: Se estudió una muestra de 75 mujeres con embarazo sano y 44 con preeclampsia (temprana n = 20, tardía n = 24). Solo las concentraciones de adipsina, leptina y factor de necrosis tumoral alfa fueron mayores en preeclampsia que en el embarazo sano [mediana (rango intercuartílico): 3.9 µg/mL (2.9-5.4) vs 2.5 µg/mL (1.9-3.1), 10.6 ng/mL (6.0-19.1) en comparación con 7.1 ng/mL (3.8-12.4), 3.6 pg/mL (2.7-5.8) vs 2.9 (2.3-3.5), respectivamente]. Las concentraciones de las adipocinas no se correlacionaron con el índice de masa corporal previo al embarazo ni con la ganancia de peso gestacional. No hubo diferencias significativas en las concentraciones entre los subtipos de preeclampsia. CONCLUSIÓN: En el tercer trimestre del embarazo la preeclampsia se asocia con un perfil sérico de adipocinas alterado, caracterizado por concentraciones elevadas de adipsina, leptina y factor de necrosis tumoral alfa, que no se relaciona con el índice de masa corporal previo al embarazo, la ganancia de peso gestacional y el subtipo de preeclampsia.

Abstract OBJECTIVES: To evaluate maternal serum concentrations of adipokines: adiponectin, adipsin, leptin, lipocalin-2, monocyte chemoattractant protein-1, nerve growth factor, resistin and tumor necrosis factor-alpha and their relationship with pre-pregnancy body mass index and gestational weight gain in women with preeclampsia compared with healthy women, and to perform an analysis classifying preeclampsia as early and late. MATERIALS AND METHODS: Cross-sectional, comparative, retrolective, non-probabilistic convenience sampling study carried out in patients attended at the Hospital de Gineco-Obstetricia 3, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS). Preoperatively, a blood sample was taken to determine serum adipokine concentrations by multianalyte assays. RESULTS: A sample of 75 women with healthy pregnancy and 44 with preeclampsia (early n = 20, late n = 24) was studied. Only adipsin, leptin, and tumor necrosis factor-alpha concentrations were higher in preeclampsia than in healthy pregnancy [median (interquartile range): 3. 9 µg/mL (2.9-5.4) vs. 2.5 µg/mL (1.9-3.1), 10.6 ng/mL (6.0-19.1) compared to 7.1 ng/mL (3.8-12.4), 3.6 pg/mL (2.7-5.8) vs. 2.9 (2.3-3.5), respectively]. Adipokine concentrations did not correlate with pre-pregnancy body mass index and gestational weight gain. There were no significant differences in concentrations between preeclampsia subtypes. CONCLUSION: In the third trimester of pregnancy, preeclampsia is associated with an altered serum adipokine profile, characterized by elevated concentrations of adipsin, leptin, and tumor necrosis factor-alpha, which is not related to prepregnancy body mass index, gestational weight gain, and preeclampsia subtype.