Maternal Stress during Pregnancy in Mice Induces Sex-Dependent Behavioral Alterations in Offspring along with Impaired Serotonin and Kynurenine Pathways of Tryptophan Metabolism.

Maternal stress during pregnancy results in increased risk of developing psychiatric disorders in the offspring including anxiety, depression, schizophrenia, and autism. However, the mechanisms underlying this disease susceptibility remain largely to be determined. In this study, the involvement of the serotonin (5-HT) and kynurenine (KYN) pathways of tryptophan metabolism on the behavioral deficits induced by maternal stress during the late phase of gestation in mice was investigated. Adult offspring born to control or restraint-stressed dams were exposed to the elevated plus-maze and tail suspension tests. Metabolites of the KYN and 5-HT pathways were measured in the hippocampus and brainstem by ultra-performance liquid chromatography tandem mass spectrometry. Female, but not male, prenatally stressed (PNS) offspring displayed a depressive-like phenotype, mainly when in proestrus/diestrus, along with reduced hippocampal 5-HT levels and high 5-HT turnover rate in the hippocampus and brainstem. In contrast, male PNS mice showed enhanced anxiety-like behaviors and higher hippocampal and brainstem quinolinic acid levels compared to male offspring born to nonstressed dams. These results indicate that maternal stress affects the behavior and brain metabolism of tryptophan in the offspring in a sex-dependent manner and suggest that alterations in both the 5-HT and KYN pathways may underlie the emotional dysfunctions observed in individuals exposed to stress during in utero development.

DHA Supplementation of Obese Rats throughout Pregnancy and Lactation Modifies Milk Composition and Anxiety Behavior of Offspring.

We investigated if supplementing obese mothers (MO) with docosahexaenoic acid (DHA) improves milk long-chain polyunsaturated fatty acid (LCPUFA) composition and offspring anxiety behavior. From weaning throughout pregnancy and lactation, female Wistar rats ate chow (C) or a high-fat diet (MO). One month before mating and through lactation, half the mothers received 400 mg DHA kg-1 d-1 orally (C+DHA or MO+DHA). Offspring ate C after weaning. Maternal weight, total body fat, milk hormones, and milk nutrient composition were determined. Pups' milk nutrient intake was evaluated, and behavioral anxiety tests were conducted. MO exhibited increased weight and total fat, and higher milk corticosterone, leptin, linoleic, and arachidonic acid (AA) concentrations, and less DHA content. MO male and female offspring had higher ω-6/ ω-3 milk consumption ratios. In the elevated plus maze, female but not male MO offspring exhibited more anxiety. MO+DHA mothers exhibited lower weight, total fat, milk leptin, and AA concentrations, and enhanced milk DHA. MO+DHA offspring had a lower ω-6/ω-3 milk intake ratio and reduced anxiety vs. MO. DHA content was greater in C+DHA milk vs. C. Supplementing MO mothers with DHA improves milk composition, especially LCPUFA content and ω-6/ω-3 ratio reducing offspring anxiety in a sex-dependent manner.

Indicadores socioeconómicos de obesidad materna. El estudio de una cohorte en Morelos, México / Socioeconomic indicators of maternal obesity. Study of a cohort in Morelos, México / Indicadores socioeconómicos da obesidade materna. Estudo de uma coorte no Morelos, México / Indicateurs socio-économiques de l'obésité maternelle. Étude d'une cohorte au Morelos, Mexique

Resumen: Objetivo: Identificar y analizar desde una perspectiva cuanti/cualitativita los indicadores socioeconómicos de la obesidad materna en México. Material y métodos: Investigación evaluativa basada en un diseño de cohorte de tipo prospectivo/descriptivo. El tamaño de la muestra se conformó por todas las mujeres que llegaron a consulta prenatal a partir de la semana 24 de gestación en un hospital de referencia estatal. El tamaño de la muestra se estimó con un 80% de poder y 95% de confianza y significancia. Los indicadores de interés fueron aspectos socioeconómicos, alimentación, antropometría, dieta, seguridad alimentaria y actividad física. El análisis cuantitativo se realizó utilizando el software Stata versión 14 y el análisis cualitativo con Atlas-ti versión 8.0. Resultados: La cohorte estuvo conformada por 402 mujeres embarazadas en 2017. De los resultados principales encontramos que el 55% de las mujeres se encontraba en el rango de edad de 18-24 años; el 15% de las mujeres refirió contar con un empleo remunerado; el 42% de la población tenía secundaria completa; el 32.1% presentó un grado de inseguridad alimentaria; la media de IMC fue de 27.8±4.8, el 48% de las mujeres presentaron sobrepeso y obesidad. Conclusiones: Los resultados cuantitativos sugieren que poblaciones con mayor vulnerabilidad socio-económica, inseguridad alimentaria y escasa actividad física, son más propensas a la obesidad materna. Los resultados cualitativos, además de complementar y reforzar los resultados cuantitativos, plantean evidencias para identificar a mayor detalle las barreras y facilitadores para fortalecer programas de intervención en la prevención de la obesidad materna.

Abstract; Objective: To identify and analyze from a quantitative / qualitative perspective the socioeconomic indicators of maternal obesity in Mexico. Methods and material: Evaluative research based on a prospective / analytical cohort design. The sample size was established by all the women who came to the antenatal clinic from the 24th week of gestation in a state referral hospital. The sample size was estimated with 80% power and 95% confidence and significance. The indicators of interest were socioeconomic aspects, nutrition, anthropometry, diet, food safety and physical activity. The quantitative analysis was performed using the Stata version 14 software and the qualitative analysis with Atlas-ti version 8.0. Results: The cohort was comprised of 402 pregnant women in 2017. From the main results we found that 55% of the women were in the age range of 18-24 years; 15% of women reported having a paid job; 42% of the population had full secondary education; 32.1% presented a degree of food insecurity; the mean BMI was 27.8 ± 4.8, 48% of the women were overweight and obese. Conclusions: Quantitative results suggest that populations with greater socio-economic vulnerability, food insecurity and low physical activity are more prone to maternal obesity. The qualitative results, besides complementing and reinforcing the quantitative results, present evidence to identify in greater detail the barriers and facilitators to strengthen intervention programs in the prevention of maternal obesity.

Resumo: Objetivo: Identificar e analisar, de uma perspectiva quantitativa / qualitativa, os indicadores socioeconômicos da obesidade materna no México. Materiais e métodos: Pesquisa avaliativa baseada em um desenho de coorte prospectivo / analítico. O tamanho da amostra foi estabelecido por todas as mulheres que chegaram à clínica pré-natal a partir da 24a semana de gestação em um hospital estadual de referência. O tamanho da amostra foi estimado com 80% de poder e 95% de confiança e significância. Os indicadores de interesse foram aspectos socioeconómicos, nutrição, antropometria, dieta, segurança alimentar e atividade física. A análise quantitativa foi realizada utilizando o software Stata versão 14 e a análise qualitativa com Atlas-ti versão 8.0. Resultados: A coorte foi composta por 402 gestantes em 2017. Dos principais resultados, constatou-se que 55% das mulheres encontravam- se na faixa etária de 18 a 24 anos; 15% das mulheres relataram ter um emprego remunerado; 42% da população tinha ensino secundário completo; 32,1% apresentaram grau de insegurança alimentar; a média do IMC foi de 27,8 ± 4,8, 48% das mulheres estavam acima do peso e obesas. Conclusões: Os resultados quantitativos sugerem que populações com maior vulnerabilidade socioeconómica, insegurança alimentar e baixa atividade física são mais propensas à obesidade materna. Os resultados qualitativos, além de complementar e reforjar os resultados quantitativos, apresentam evidencias para identificar em maior detalhe as barreiras e facilitadores para fortalecer os programas de intervenção na prevenção da obesidade materna.

Résumé: Objectif: Identifier et analyser d'un point de vue quantitatif / qualitatif les indicateurs socio-économiques de l'obésité maternelle au Mexique. Matériel et méthodes: Recherche évaluative basée sur une conception de cohorte prospective / analytique. La taille de l'échantillon a été établie par toutes les femmes qui sont venues á la clinique prénatale á partir de la 24e semaine de gestation dans un hópital de référence. La taille de l'échantillon a été estimée avec 80% de puissance et 95% de confiance et de signification. Les indicateurs d'intéret étaient les aspects socio-économiques, la nutrition, l'anthropométrie, l'alimentation, la sécurité alimentaire et l'activité physique. L'analyse quantitative a été réalisée á l'aide du logiciel Stata version 14 et de l'analyse qualitative avec Atlas-ti version 8.0. Résultats: La cohorte était composée de 402 femmes enceintes en 2017. D'aprés les principaux résultats, nous avons constaté que 55% des femmes étaient agées de 18 á 24 ans; 15% des femmes ont déclaré avoir un travail rémunéré; 42% de la population ont fait des études secondaires complétes; 32,1% présentaient un degré d'insécurité alimentaire; l'IMC moyen était de 27,8 ± 4,8, 48% des femmes étaient en surpoids et obéses. Conclusions: Les résultats quantitatifs suggérent que les populations ayant une plus grande vulnérabilité socio-économique, l'insécurité alimentaire et une faible activité physique sont plus sujettes á l'obésité maternelle. Les résultats qualitatifs, en plus de compléter et de renforcer les résultats quantitatifs, présentent des preuves pour identifier plus en détail les obstacles et les facilitateurs pour renforcer les programmes d'intervention dans la prévention de l'obésité maternelle.

Socio-economic indicators, dietary patterns, and physical activity as determinants of maternal obesity in middle-income countries: Evidences from a cohort study in Mexico.

Maternal obesity is one of the main public health problems at a world level. It is a multifactorial disease with multiple causes, and few studies exist on its dietary patterns, physical activity and social determinants. This work aims to identify determinants of maternal obesity in a middle income country. Research is based on a prospective cohort design. Data were collected using questionnaires applied to pregnant women. Three dietary patterns were identified, and only half of the women carry out physical activity. The regression analysis showed an association between overweight/obesity and the following variables: age 25 to 29 years old (3.8; CI 1.6-9.0), 30 to 34 years old (3.7; CI 1.2-11.6); health problems during pregnancy (2.1; CI 1.0-4.1); socio-economic income (1.73; CI 1.54-2.05); hypertension (2.7; CI 1.4-4.5); mild food insecurity (1.9; CI 1.0-3.8); moderate insecurity (3.7; CI 0.92-15.4); refined food dietary pattern (.76; CI.61-.95). The risk of increasing BMI during pregnancy mainly depends on socioeconomic and demographic variables such as age, educational level, income, food insecurity, and dietary pattern. This study's results could be used as evidences for the revision, planning, and adjustment of interventions for the prevention and management of maternal obesity, as a part of the national strategies against overweight and obesity.

[Socioeconomic determinants of maternal obesity in Mexico and France. Comparative analysis of two cohorts]. / Indicadores socioeconómicos de la obesidad materna en México y Francia. Análisis comparado de dos cohortes.

OBJECTIVE: To identify and analyze the socioeconomic indicators of maternal obesity in Mexico and France. MATERIAL AND METHODS: Comparative study of two cohorts: EDEN (France) and NUTTSEA (Mexico). The study population consisted of women who requested prenatal consultation at week 24 of pregnancy. Data were collected using questionnaires and semi-structured interviews. The variables of interest were socioeconomic aspects, nutrition, anthropometry and food security. The quantitative analysis was performed using Stata and the qualitative analysis with Atlas-ti. RESULTS: In the EDEN cohort, 68.6% were aged 25-34 years, 73% had paid employment and 53% completed high school. In addition, 6.6% reported having difficulty accessing food and the mean gestational BMI was 23.23 ± 4.6. In the NUTTSEA cohort, 55% were in the age range 18-24 years, 15% reported having paid employment, 42% had completed secondary education, 32.1% presented a degree of food insecurity, and the mean BMI was 27.8 ± 4.8. CONCLUSIONS: The qualitative and quantitative results of both cohorts suggest that populations with greater socio-economic vulnerability are more prone to maternal obesity, which leads to determine guidelines on barriers and facilitators to strengthen programs to prevent it maternal obesity.

OBJETIVO: Identificar y analizar los indicadores socioeconómicos de obesidad materna en México y Francia. METODOLOGÍA: Estudio comparativo de dos cohortes EDEN sus siglas en francés (Etude des déterminants pré et post natals précoces de la santé et de développement de l'enfant) (Francia) y NUTTSEA (México). La población de estudio se conformó por mujeres que solicitaron consulta prenatal en semana 24 de gestación. Los datos fueron recolectados con cuestionarios y entrevistas semi-estructuradas. Las variables de interés fueron aspectos socioeconómicos, alimentación, antropometría y seguridad alimentaria. El análisis cuantitativo se realizó utilizando Stata y el análisis cualitativo con Atlas-ti. RESULTADOS: En cohorte EDEN el 68.6% resultó con edad de 25-34 años, el 73% tenían un empleo remunerado, el 53% preparatoria completa; el 6.6% refirió tener dificultad para acceder a los alimentos; la media del IMC gestacional fue de 23.23±4.6. En la cohorte NUTTSEA el 55% se encontraba en el rango de edad de 18-24 años; el 15% refirió contar con un empleo remunerado; el 42% de la población tenía secundaria completa; el 32.1% presentó un grado de inseguridad alimentaria; la media de IMC fue de 27.8±4.8. CONCLUSIONES: Los resultados cuali-cuantitativos de ambas cohortes sugieren que poblaciones con mayor vulnerabilidad socio-económica son más propensas a la obesidad materna, determinando directrices sobre barreras y facilitadores para fortalecer programas de prevención de la obesidad materna.

Indicadores socioeconómicos de la obesidad materna en México y Francia: análisis comparado de dos cohortes / Socioeconomic determinants of maternal obesity in Mexico and France: comparative analysis of two cohorts

RESUMEN Objetivo Identificar y analizar los indicadores socioeconómicos de obesidad materna en México y Francia. Metodología Estudio comparativo de dos cohortes EDEN sus siglas en francés (Etude des déterminants pré et post natals précoces de la santé et de développement de l'enfant) (Francia) y NUTTSEA (México). La población de estudio se conformó por mujeres que solicitaron consulta prenatal en semana 24 de gestación. Los datos fueron recolectados con cuestionarios y entrevistas semi-estructuradas. Las variables de interés fueron aspectos socioeconómicos, alimentación, antropometría y seguridad alimentaria. El análisis cuantitativo se realizó utilizando Stata y el análisis cualitativo con Atlas-ti. Resultados En cohorte EDEN el 68.6% resultó con edad de 25-34 años, el 73% tenían un empleo remunerado, el 53% preparatoria completa; el 6.6% refirió tener dificultad para acceder a los alimentos; la media del IMC gestacional fue de 23.23±4.6. En la cohorte NUTTSEA el 55% se encontraba en el rango de edad de 18-24 años; el 15% refirió contar con un empleo remunerado; el 42% de la población tenía secundaria completa; el 32.1% presentó un grado de inseguridad alimentaria; la media de IMC fue de 27.8±4.8. Conclusiones Los resultados cuali-cuantitativos de ambas cohortes sugieren que poblaciones con mayor vulnerabilidad socio-económica son más propensas a la obesidad materna, determinando directrices sobre barreras y facilitadores para fortalecer programas de prevención de la obesidad materna.(AU)

ABSTRACT Objective To identify and analyze the socioeconomic indicators of maternal obesity in Mexico and France. Material and Methods Comparative study of two cohorts: EDEN (France) and NUTTSEA (Mexico). The study population consisted of women who requested prenatal consultation at week 24 of pregnancy. Data were collected using questionnaires and semi-structured interviews. The variables of interest were socioeconomic aspects, nutrition, anthropometry and food security. The quantitative analysis was performed using Stata and the qualitative analysis with Atlas-ti. Results In the EDEN cohort, 68.6% were aged 25-34 years, 73% had paid employment and 53% completed high school. In addition, 6.6% reported having difficulty accessing food and the mean gestational BMI was 23.23 ± 4.6. In the NUTTSEA cohort, 55% were in the age range 18-24 years, 15% reported having paid employment, 42% had completed secondary education, 32.1% presented a degree of food insecurity, and the mean BMI was 27.8 ± 4.8. Conclusions The qualitative and quantitative results of both cohorts suggest that populations with greater socio-economic vulnerability are more prone to maternal obesity, which leads to determine guidelines on barriers and facilitators to strengthen programs to prevent it maternal obesity.(AU)

Abnormality of adipokines and endothelial dysfunction in Mexican obese adolescents with insulin resistance.

PURPOSE: The aim of this study was to investigate the possible relationship among insulin resistance (IR), endothelial dysfunction, and alteration of adipokines in Mexican obese adolescents and their association with metabolic syndrome (MetS). MATERIALS AND METHODS: Two hundred and twenty-seven adolescents were classified according to the body mass index (BMI) (control: N=104; obese: N=123) and homeostasis model of the assessment-insulin resistance index (HOMA-IR) (obese with IR: N=65). The circulating concentrations of leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), and IR were determined by standard methods. RESULTS: The obese adolescents with IR presented increased presence of MetS and higher circulating concentrations in sICAM-1 in comparison with the obese subjects without IR. The lowest concentrations of adiponectin were observed in the obese with IR. In multivariate linear regression models, sICAM-1 along with triglycerides, total cholesterol, and waist circumference was strongly associated with HOMA-IR (R2=0.457, P=0.008). Similarly, after adjustment for age, BMI-SDS, lipids, and adipokines, HOMA-IR remained associated with sICAM-1 (R2=0.372, P=0.008). BMI-SDS was mildly associated with leptin (R2=0.176, P=0.002) and the waist circumference was mild and independent determinant of adiponectin (R2=0.136, P=0.007). CONCLUSIONS: Our findings demonstrated that the obese adolescents, particularly the obese subjects with IR exhibited increased presence of MetS, abnormality of adipokines, and endothelial dysfunction. The significant interaction between IR and endothelial dysfunction may suggest a novel therapeutic approach to prevent or delay systemic IR and the genesis of cardiovascular diseases in obese patients.

Paternal selenium deficiency but not supplementation during preconception alters mammary gland development and 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in female rat offspring.

Breast cancer is a global public health problem and accumulating evidence indicates early-life exposures as relevant factors in the disease risk determination. Recent studies have shown that paternal nutrition can influence offspring health including breast cancer risk. Selenium is a micronutrient with essential role in central aspects of embryogenesis, male fertility and cancer and that has been extensively studied as a chemopreventive agent in several breast cancer experimental models. Thus, we designed an animal study to evaluate whether paternal selenium deficiency or supplementation during preconception could affect the female offspring mammary gland development and breast cancer susceptibility. Male Sprague-Dawley rats were fed AIN93-G diet containing 0.15 ppm (control diet), 0.05 ppm (deficient diet) or 1 ppm (supplemented diet) of selenium for 9 weeks and mated with control female rats. Mammary carcinogenesis was induced with 7,12-dimethylbenz[a]anthracene (DMBA) in their female offspring. Paternal selenium deficiency increased the number of terminal end buds, epithelial elongation and cell proliferation in the mammary gland of the female rat offspring and these effects were associated with higher susceptibility to DMBA-induced mammary tumors (increased incidence and higher grade tumors). On the other hand, paternal selenium supplementation did not influence any of these parameters. These results highlight the importance of father's nutrition including selenium status as a relevant factor affecting daughter's breast cancer risk and paternal preconception as a potential developmental stage to start disease preventive strategies.

Long-lasting effect of perinatal exposure to L-tryptophan on circadian clock of primary cell lines established from male offspring born from mothers fed on dietary protein restriction.

BACKGROUND AIMS: Maternal undernutrition programs metabolic adaptations which are ultimately detrimental to adult. L-tryptophan supplementation was given to manipulate the long-term sequelae of early-life programming by undernutrition and explore whether cultured cells retain circadian clock dysregulation. METHODS: Male rat pups from mothers fed on low protein (8%, LP) or control (18%, CP) diet were given, one hour before light off, an oral bolus of L-tryptophan (125 mg/kg) between Day-12 and Day-21 of age. Body weight, food intake, blood glucose along with the capacity of colonization of primary cells from biopsies were measured during the young (45-55 days) and adult (110-130 days) phases. Circadian clock oscillations were re-induced by a serum shock over 30 hours on near-confluent cell monolayers to follow PERIOD1 and CLOCK proteins by Fluorescent Linked ImmunoSorbent Assay (FLISA) and period1 and bmal1 mRNA by RT-PCR. Cell survival in amino acid-free conditions were used to measure circadian expression of MAP-LC3B, MAP-LC3B-FP and Survivin. RESULTS: Tryptophan supplementation did not alter body weight gain nor feeding pattern. By three-way ANOVA of blood glucose, sampling time was found significant during all phases. A significant interaction between daily bolus (Tryptophan, saline) and diets (LP, CP) were found during young (p = 0.0291) and adult (p = 0.0285) phases. In adult phase, the capacity of colonization at seeding of primary cells was twice lower for LP rats. By three-way ANOVA of PERIOD1 perinuclear/nuclear immunoreactivity during young phase, we found a significant effect of diets (p = 0.049), daily bolus (p<0.0001) and synchronizer hours (p = 0.0002). All factors were significantly interacting (p = 0.0148). MAP-LC3B, MAP-LC3B-FP and Survivin were altered according to diets in young phase. CONCLUSIONS: Sequelae of early-life undernutrition and the effects of L-tryptophan supplementation can be monitored non-invasively by circadian sampling of blood D-glucose and on the expression of PERIOD1 protein in established primary cell lines.