Prenatal exposure to titanium dioxide nanoparticles induces persistent neurobehavioral impairments in maternal mice that is associated with microbiota-gut-brain axis.

Gestational exposure to titanium dioxide nanoparticles (TiO2NPs) has been widely reported to have deleterious effects on the brain functions of offspring. However, little attention has been paid to the neurotoxic effects of TiO2NPs on maternal body after parturition. The pregnant mice were orally administrated with TiO2NPs at 150 mg/kg from gestational day 8-21. The potential effects of TiO2NPs on the neurobehaviors were evaluated at postnatal day 60. The gut microbiota, morphological alterations of intestine and brain, and other indicators that involved in gut-brain axis were all assessed to investigate the underlying mechanisms. The results demonstrated that exposure to TiO2NPs during pregnancy caused the persistent neurobehavioral impairments of maternal mice after delivery for 60 days, mainly including behavioural changes, pathological changes in hippocampus, cortex and intestine. Our data also showed that persistent dysfunction and tissue injuries were probably associated with the disruption of gut-brain axis, manifested by the shift in the composition of gut microbial community, alteration of Sstr1, inhibition of enteric neurons and reduction of diamine oxidase contents in maternal mice. These findings provide a novel insight that regulation of gut microecology may be an alternative strategy for the protection against the neurotoxicity of TiO2NPs in pregnant women.

Developmental exposure of California mice to endocrine disrupting chemicals and potential effects on the microbiome-gut-brain axis at adulthood.

Xenoestrogens are chemicals found in plant products, such as genistein (GEN), and in industrial chemicals, e.g., bisphenol A (BPA), present in plastics and other products that are prevalent in the environment. Early exposure to such endocrine disrupting chemicals (EDC) may affect brain development by directly disrupting neural programming and/or through the microbiome-gut-brain axis. To test this hypothesis, California mice (Peromyscus californicus) offspring were exposed through the maternal diet to GEN (250 mg/kg feed weight) or BPA (5 mg/kg feed weight, low dose- LD or 50 mg/kg, upper dose-UD), and dams were placed on these diets two weeks prior to breeding, throughout gestation, and lactation. Various behaviors, gut microbiota, and fecal metabolome were assessed at 90 days of age. The LD but not UD of BPA exposure resulted in individuals spending more time engaging in repetitive behaviors. GEN exposed individuals were more likely to exhibit such behaviors and showed socio-communicative disturbances. BPA and GEN exposed females had increased number of metabolites involved in carbohydrate metabolism and synthesis. Males exposed to BPA or GEN showed alterations in lysine degradation and phenylalanine and tyrosine metabolism. Current findings indicate cause for concern that developmental exposure to BPA or GEN might affect the microbiome-gut-brain axis.

[Non-caloric sweeteners in women of reproductive age - A consensus document]. / Edulcorantes no calóricos en la mujer en edad reproductiva: documento de consenso.

INTRODUCTION: Non-nutritive sweeteners (NNS) are food additives that have been used as a possible tool to reduce energy and sugar intake. There is a scientific debate around the real benefits of their use. NNS are substances widely evaluated in the scientific literature. Their safety is reviewed by international regulatory health agencies. Health professionals and consumers often lack education and objective information about food additives based on the best scientific evidence. NNS have been used as a substitute for sucrose, especially by people with diabetes mellitus and obesity. However, concerns related to their possible association with preterm birth have been raised, and also with their use during pregnancy and lactation because of the possibility of metabolic or other consequences in both the mother and offspring. This analysis of the evidence in gynecology and obstetrics presents a review of the most commonly asked questions regarding this matter by health professionals and their patients. This document evaluates a diversity of scientific publications under the sieve of evidence-based medicine and the regulatory framework for food additives to elucidate whether the use of NNS in women in these critical stages of pregnancy and breastfeeding represents a potential risk.

INTRODUCCIÓN: Los edulcorantes no calóricos (ENC) son aditivos de alimentos que se utilizan para sustituir azúcares y potencialmente para reducir la ingesta energética. Existe un debate científico en torno a los beneficios reales de su uso. Los ENC son sustancias ampliamente evaluadas en la literatura científica. Su seguridad es revisada por las agencias regulatorias internacionales del campo de la salud. Los profesionales de la salud y los consumidores con frecuencia carecen de educación e información rigurosa, objetiva y sustentada en la evidencia científica y el juicio clínico sobre el uso de aditivos en los alimentos. Los ENC se han empleado como sustitutos de la sacarosa, en especial por las personas con diabetes mellitus y obesidad. Sin embargo, se han planteado inquietudes relacionadas con su posible asociación con el parto pretérmino y con su uso durante el embarazo y la lactancia, ante la posibilidad de consecuencias metabólicas o de otra índole en la madre o en el neonato. Este análisis de la evidencia en ginecología y obstetricia presenta una revisión que intenta responder a preguntas que habitualmente se hacen al respecto los profesionales de la salud y sus pacientes. En este documento se evalúan diversas publicaciones científicas bajo el tamiz de la medicina basada en la evidencia y del marco regulatorio para aditivos de alimentos con el fin dilucidar si el uso de ENC en las mujeres durante las etapas críticas del embarazo y la lactancia supone o no un posible riesgo.

Preconception Exposure to Fine Particulate Matter Leads to Cardiac Dysfunction in Adult Male Offspring.

Background Particulate matter (particles < 2.5 µm [ PM 2.5]) exposure during the in utero and postnatal developmental periods causes cardiac dysfunction during adulthood. Here, we investigated the potential priming effects of preconception exposure of PM 2.5 on cardiac function in adult offspring. Methods and Results Male and female friend leukemia virus b (FVB) mice were exposed to either filtered air ( FA ) or PM 2.5 at an average concentration of 38.58 µg/m3 for 6 hours/day, 5 days/week for 3 months. Mice were then crossbred into 2 groups: (1)  FA male× FA female (both parents were exposed to FA preconception) and, (2) PM 2.5male× PM 2.5female (both parents were exposed to PM 2.5 preconception). Male offspring were divided: (1) preconception FA (offspring born to FA exposed parents) and, (2) preconception PM 2.5 (offspring born to PM 2.5 exposed parents) and analyzed at 3 months of age. Echocardiography identified increased left ventricular end systolic volume and reduced posterior wall thickness, reduced %fractional shortening and %ejection fraction in preconception PM 2.5 offspring. Cardiomyocytes isolated from preconception PM 2.5 offspring showed reduced %peak shortening, -dL/dT, TPS 90 and slower calcium reuptake (tau). Gene and protein expression revealed modifications in markers of inflammation ( IL -6, IL -15, TNF α, NF қB, CRP , CD 26E, CD 26P, intercellular adhesion molecule 1, and monocyte chemoattractant protein-1) profibrosis (collagen type III alpha 1 chain), oxidative stress ( NOS 2), antioxidants (Nrf2, SOD , catalase), Ca2+ regulatory proteins ( SERCA 2a, p- PLN , NCX ), and epigenetic regulators (Dnmt1, Dnmt3a, Dnmt3b, Sirt1, and Sirt2) in preconception PM 2.5 offspring. Conclusions Preconception exposure to PM 2.5 results in global cardiac dysfunction in adult offspring, suggesting that abnormalities during development are not limited to the prenatal or postnatal periods but can also be determined before conception.

Possible association between acetazolamide administration during pregnancy and multiple congenital malformations.

Congenital malformations might occur because of environmental or genetic factors, and sometimes occur because of unknown causes. Acetazolamide is a carbonic anhydrase inhibitor that is used to treat idiopathic intracranial hypertension, glaucoma, and epilepsy. The use of acetazolamide has not been recommended for pregnant women because of reported teratogenic risks. Congenital malformations, such as ectrodactyly, syndactyly, cleft lip/palate, and retarded incisor teeth development, have been reported in experimental animals. However, tooth agenesis due to the use of acetazolamide has not been reported yet. Oligodontia is a severe type of tooth agenesis involving six or more congenitally missing teeth. The causes of oligodontia are attributed to environmental factors, such as irradiation, drugs, trauma, tumors, infection, genetic factors, or a combination. There is no credible evidence of undesirable effects of acetazolamide use in human pregnancy. However, we report a case of a 12-year-old Saudi boy who was exposed to maternal acetazolamide (1,000 mg/day) for treatment of idiopathic intracranial hypertension before pregnancy, during the first trimester, and throughout the pregnancy. This treatment might have resulted in some congenital malformations, such as ectrodactyly, syndactyly, and oligodontia.

Investigating paternal preconception risk factors for adverse pregnancy outcomes in a population of internet users.

BACKGROUND: Paternal preconception risk factors such as smoking, exposure to environmental substances, medication use, overweight and advanced age correlate with the occurrence of malformations and birth defects in the offspring. Nonetheless, the prevalence of risk factors for adverse pregnancy outcomes in the male population has been scarcely investigated and no report on preconception interventions targeting prospective fathers is available. We conducted a web-based survey to measure the prevalence of paternal preconception risk factors for adverse pregnancy outcomes in an Italian population of Internet users. METHODS: Prospective or expectant fathers were enrolled during a four-week period through two of the main Italian web-sites dedicated to preconception, pregnancy, childhood and family care. Participants filled in a web questionnaire regarding preconception risk factors for adverse pregnancy outcomes. Logistic regression analysis was used to explore the predictors of paternal preconception risk factors. RESULTS: We enrolled 131 prospective and 205 expectant fathers. More than half of the total participants used medications during the preconception period, 35% were smokers and 8% were obese. Exposure to environmental substances was declared by almost 20% of the participants, with the group including pesticides/herbicides/professional paints being the most prevalent. More than a half of the study sample included men aged over 35 years. According to the multivariate analysis, smoking and exposure to environmental toxics were less frequent among individuals with a university degree (respectively: OR = 0.52; 95% CI 0.32-0.84; OR = 0.52; 95% CI 0.29-0.93). Paternal obesity and medication use in the preconception period were not associated with any of the independent variables. CONCLUSIONS: The prevalence of preconception risk factors among male population should not be neglected when planning preconception interventions, confirming that preconception health must be focused on the couple, rather than on women only.

No excess risks in offspring with paternal preconception exposure to disease-modifying antirheumatic drugs.

OBJECTIVE: To examine pregnancy outcomes in the partners of male patients with inflammatory joint disease who were or were not exposed to disease-modifying antirheumatic drugs (DMARDs) before conception compared with the outcomes in reference subjects from the general population. METHODS: Linkage of data from a longitudinal observational study of patients with inflammatory joint disease (the Norwegian Disease-Modifying Antirheumatic Drug [NOR-DMARD] registry study) and the Medical Birth Registry of Norway (MBRN) enabled a comparison of pregnancy outcomes in the partners of men with inflammatory joint disease. Outcomes of pregnancies in which the father was exposed to DMARDs within 12 weeks of conception and those in which the father was never exposed to DMARDs were analyzed separately and compared with the outcomes in reference subjects. Potential associations between DMARD exposure and adverse pregnancy outcomes were assessed by logistic regression analysis. RESULTS: A total of 1,796 men with inflammatory joint disease were associated with 2,777 births in the MBRN. In 110 of these births, the father had been exposed to DMARDs within 12 weeks before conception, and in 230 births the father had never been exposed to DMARDs before conception. The DMARDs (monotherapy or combination treatment) to which the fathers were exposed most frequently within 12 weeks of conception were methotrexate (n = 49), sulfasalazine (n = 17), and tumor necrosis factor inhibitors (n = 57). Neither adverse pregnancy outcomes nor occurrence of congenital malformations differed between patients and reference subjects in either group. CONCLUSION: Preconception paternal exposure to DMARDs was not associated with an increase in adverse pregnancy outcomes. Importantly, no increased risk of congenital malformations was observed.