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Maternal gut and fetal brain connection: Increased anxiety and reduced social interactions in Wistar rat offspring following peri-conceptional antibiotic exposure.

ABSTRACT: BACKGROUND:A growing body of evidence indicates that gut microbiota characteristics may be closely related to mental dysfunctions. However, no studies have investigated fetal brain development in relation to the maternal gut microbiota, despite the extensive use of antibiotics in obstetric practice. OBJECTIVE:To determine how periconceptional exposure to SuccinylSulfaThiazole (SST), a non-absorbable antibiotic, can affect behavior in rat offspring. This antibiotic drug has previously been shown to substantially perturb the gut microbiota in rats following a 28-day exposure. METHODS:Female Wistar rats were divided in two groups: control, or exposed during one month before breeding until gestational day 15 to a diet containing 1% SST. We administered behavioral tests to offspring, i.e., open field (post-natal day 20), social interactions (P25), marble burying (P30), elevated plus maze (P35), and prepulse inhibition of the acoustic startle reflex (sensory gating) (P45). RESULTS:Both male and female offspring exposed peri-conceptionally to SST showed reduced social interactions, with a decrease of about half in time spent in social interactions compared to controls, reduced exploration of the open arm by 20% in the elevated plus maze test indicating increased anxiety and altered sensorimotor gating, with a 1.5-2-fold decrease in startle inhibition. CONCLUSION:Maternal periconceptional exposure to SST provokes alterations in offspring behavior in the absence of maternal infection. Because we administered SST, a non-absorbable antibiotic, only to the dam, we conclude that these neurobehavioral alterations in the offspring are related to maternal gut microbiota alterations.

SUBMITTER: Degroote S

PROVIDER: S-EPMC6584952 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Maternal gut and fetal brain connection: Increased anxiety and reduced social interactions in Wistar rat offspring following peri-conceptional antibiotic exposure.

Degroote Stéphanie S Hunting Darel J DJ Baccarelli Andrea A AA Takser Larissa L

Progress in neuro-psychopharmacology & biological psychiatry 20160621

<h4>Background</h4>A growing body of evidence indicates that gut microbiota characteristics may be closely related to mental dysfunctions. However, no studies have investigated fetal brain development in relation to the maternal gut microbiota, despite the extensive use of antibiotics in obstetric practice.<h4>Objective</h4>To determine how periconceptional exposure to SuccinylSulfaThiazole (SST), a non-absorbable antibiotic, can affect behavior in rat offspring. This antibiotic drug has previou ...[more]

PMID: 27346743

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Project description:BackgroundMaternal lack of folic acid supplementation during pregnancy may increase the risk of low birth weight and preterm delivery. However, little is known about the relationship between folic acid supplementation during pregnancy and the physical development of offspring in the later stage.ObjectiveThis study aimed to explore the association between maternal folic acid supplementation status during pregnancy and the physical development of preschool children.MethodsA total of 3064 mother-child pairs with data on maternal folic acid supplementation status during pregnancy and children's anthropometric measurements were recruited from the Ma'anshan-Anhui Birth Cohort (MABC) in China. Maternal folic acid supplementation status during pregnancy was the main exposure, and the primary outcomes were children's growth development trajectories. Children's growth development trajectories were fitted using group-based trajectory models. The association between maternal folic acid supplementation status during pregnancy and children's growth trajectories was performed using multiple logistic regression models.ResultsAfter adjusting for potential confounders, we found that the absence of maternal folic acid supplementation before pregnancy and in the first trimester was significantly associated with a "high level" trajectory (trajectory 3) and a "high rising level" trajectory (trajectory 4) of BMI-Z scores in children 0 to 6 years of age (OR = 1.423, 95%CI:1.022-1.982; OR = 1.654, 95%CI: 1.024-2.671). In children aged 4 to 6 years old, a "high level" trajectory (trajectory 3) of body fat ratio was substantially related to maternal no folic acid supplementation before pregnancy and in the first trimester (OR = 1.833, 95%CI:1.037-3.240). No significant additional benefits associated with physical developmental indicators in preschool children have been observed with continued folic acid supplementation after the first trimester of gestation.ConclusionsMaternal non-supplementation with folic acid during pregnancy is associated with a "high level" BMI trajectory and a "high level" body fat ratio trajectory in preschool-aged children.

Project description:Inositol 1,4,5-trisphosphate receptors (IP3Rs) are a family of intracellular Ca2+ release channels located on the ER membrane, which in mammals consist of 3 different subtypes (IP3R1, IP3R2, and IP3R3) encoded by 3 genes, Itpr1, Itpr2, and Itpr3, respectively. Studies utilizing genetic knockout mouse models have demonstrated that IP3Rs are essential for embryonic survival in a redundant manner. Deletion of both IP3R1 and IP3R2 has been shown to cause cardiovascular defects and embryonic lethality. However, it remains unknown which cell types account for the cardiovascular defects in IP3R1 and IP3R2 double knockout (DKO) mice. In this study, we generated conditional IP3R1 and IP3R2 knockout mouse models with both genes deleted in specific cardiovascular cell lineages. Our results revealed that deletion of IP3R1 and IP3R2 in cardiomyocytes by TnT-Cre, in endothelial / hematopoietic cells by Tie2-Cre and Flk1-Cre, or in early precursors of the cardiovascular lineages by Mesp1-Cre, resulted in no phenotypes. This demonstrated that deletion of both IP3R genes in cardiovascular cell lineages cannot account for the cardiovascular defects and embryonic lethality observed in DKO mice. We then revisited and performed more detailed phenotypic analysis in DKO embryos, and found that DKO embryos developed cardiovascular defects including reduced size of aortas, enlarged cardiac chambers, as well as growth retardation at embryonic day (E) 9.5, but in varied degrees of severity. Interestingly, we also observed allantoic-placental defects including reduced sizes of umbilical vessels and reduced depth of placental labyrinth in DKO embryos, which could occur independently from other phenotypes in DKO embryos even without obvious growth retardation. Furthermore, deletion of both IP3R1 and IP3R2 by the epiblast-specific Meox2-Cre, which targets all the fetal tissues and extraembryonic mesoderm but not extraembryonic trophoblast cells, also resulted in embryonic lethality and similar allantoic-placental defects. Taken together, our results demonstrated that IP3R1 and IP3R2 play an essential and redundant role in maintaining the integrity of fetal-maternal connection and embryonic viability.

Dataset Information

Maternal gut and fetal brain connection: Increased anxiety and reduced social interactions in Wistar rat offspring following peri-conceptional antibiotic exposure.

Publications

Maternal gut and fetal brain connection: Increased anxiety and reduced social interactions in Wistar rat offspring following peri-conceptional antibiotic exposure.

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