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. 2023 Apr 4:14:1069243.
doi: 10.3389/fendo.2023.1069243. eCollection 2023.

Maternal exposure to air pollution alters energy balance transiently according to gender and changes gut microbiota

Olivia Pizetta Zordão  1 , Clara Machado Campolim  1 , Victor Yuji Yariwake  2 , Gisele Castro  1 , Clílton Kraüss de Oliveira Ferreira  3 , Andrey Santos  1 , Sónia Norberto  1 , Mariana Matera Veras  2 , Mario Jose Abdalla Saad  1 , Paulo Hilário Nascimento Saldiva  2 , Young-Bum Kim  4 , Patricia Oliveira Prada  1   3
Affiliations

Maternal exposure to air pollution alters energy balance transiently according to gender and changes gut microbiota

Olivia Pizetta Zordão et al. Front Endocrinol (Lausanne). .

Abstract

Introduction: The timing of maternal exposure to air pollution is crucial to define metabolic changes in the offspring. Here we aimed to determine the most critical period of maternal exposure to particulate matter (PM2.5) that impairs offspring's energy metabolism and gut microbiota composition.

Methods: Unexposed female and male C57BL/6J mice were mated. PM2.5 or filtered air (FA) exposure occurred only in gestation (PM2.5/FA) or lactation (FA/PM2.5). We studied the offspring of both genders.

Results: PM2.5 exposure during gestation increased body weight (BW) at birth and from weaning to young in male adulthood. Leptin levels, food intake, Agrp, and Npy levels in the hypothalamus were also increased in young male offspring. Ikbke, Tnf increased in male PM2.5/FA. Males from FA/PM2.5 group were protected from these phenotypes showing higher O2 consumption and Ucp1 in the brown adipose tissue. In female offspring, we did not see changes in BW at weaning. However, adult females from PM2.5/FA displayed higher BW and leptin levels, despite increased energy expenditure and thermogenesis. This group showed a slight increase in food intake. In female offspring from FA/PM2.5, BW, and leptin levels were elevated. This group displayed higher energy expenditure and a mild increase in food intake. To determine if maternal exposure to PM2.5 could affect the offspring's gut microbiota, we analyzed alpha diversity by Shannon and Simpson indexes and beta diversity by the Linear Discriminant Analysis (LDA) in offspring at 30 weeks. Unlike males, exposure during gestation led to higher adiposity and leptin maintenance in female offspring at this age. Gestation exposure was associated with decreased alpha diversity in the gut microbiota in both genders.

Discussion: Our data support that exposure to air pollution during gestation is more harmful to metabolism than exposure during lactation. Male offspring had an unfavorable metabolic phenotype at a young age. However, at an older age, only females kept more adiposity. Ultimately, our data highlight the importance of controlling air pollution, especially during gestation.

Keywords: PM2.5; air pollution; gestation; gut microbiota; inflammation; metabolic program; obesity; particulate matter.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Maternal exposure to PM2.5 alters the energy metabolism of the offspring. (A) Male offspring body weight (g) at weaning, n=6-10. (B) Male offspring body weight (g), n=17-26. (C) Female offspring body weight (g) at weaning, n=5-10. (D) Female offspring body weight (g), n=12-19. (E) Male offspring fasting serum leptin level (ηg/mL), n=5 for each group. (F) Food intake (g), n=5 for each group. (g) Female offspring fasting serum leptin level (ηg/mL), n=3-6 for each group. (H) Female offspring food intake (g), n=5 for each group. (I) Male offspring oxygen (O2) consumption (L/kg/hr), n=5-8. (J) Carbon dioxide (CO2) production (L/kg/hr), n=5-8. (K) Female offspring O2 consumption (L/kg/hr), n=5-8. L. CO2 production (L/kg/hr), n=5-8. M. Male offspring respiratory exchange ratio (RER), n=5-8. N. Uncoupling Protein 1 (Ucp1) gene expression in the brown adipose tissue (BAT), n=8-13. O. Female offspring RER, n=5-8. P. Ucp1 gene expression in the BAT, n=3-10 from female offspring. Offspring mothers were exposed to PM2.5 during pregnancy (PM2.5/FA) or lactation (FA/PM2.5) and filtered air during pregnancy and lactation (FA/FA) as a control group. Panels (B, D, E, G) mice were 8 weeks. Panels (F) and (H), mice were 13-14 weeks. Panels (I-P), mice were 18-19 weeks. Data were expressed as the mean ± SEM. One-way ANOVA was used to analyze Panels (A–E, G) and (I-P). Two-way ANOVA was used for Panels (F) and (H) We used Bonferroni as a post hoc test and a significance of P<0.05. p values: ***P<0.001; **P<0.01; *P<0.05 (PM2.5/FA vs. FA/FA); &&&P<0.001; &&P<0.01; &P<0.05 (PM2.5/FA vs. FA/PM2.5); ###P<0.001; ##P<0.01; #P<0.05 (FA/PM2.5 vs. FA/FA).
Figure 2
Figure 2
Maternal exposure to PM2.5 alters hypothalamic neuropeptide expression and pro-inflammatory signals significantly in the offspring. (A) (males): Agrp (Agouti-related protein); Npy (neuropeptide Y); and Pomc (Pro-opiomelanocortin) expression in the hypothalamus n=3-6. (B) (females): Agrp (Agouti-related protein); Npy (neuropeptide Y). And Pomc (Pro-opiomelanocortin) expression in the hypothalamus n=3-6. (C) (males): Tlr4 (Toll-like receptor 4); Ikbke and Tnf alpha (Tumor necrosis factor-alpha) expression in the hypothalamus n=4-8. (D) (females): Tlr4 (Toll-like receptor 4); ikke and Tnf alpha (Tumor necrosis factor-alpha) expression in the hypothalamus n=4-11 from offspring whose mothers were exposed to PM2.5 during pregnancy (PM2.5/FA) or lactation (FA/PM2.5) and filtered air during pregnancy and lactation (FA/FA) as a control group. All mice were 20 weeks of age. 2^delta Ct was used to determine each gene expression. Data were expressed as the mean ± SEM. One-way ANOVA was used for the statistical analysis. We used Bonferroni as a post hoc test and a significance of P<0.05. p values: *P<0.05 (PM2.5/FA vs. FA/FA); &&P<0.01 (PM2.5/FA vs. FA/PM2.5).
Figure 3
Figure 3
Maternal PM2.5 exposure alters alpha diversity and gut microbiota composition independent of gender. (A) Male body weight (g); (B) Male fat mass (g/gBW), n=23-35 and (C) Male fasting serum leptin level (ηg/mL), n=9-19. (D) Female body weight (g); (E) Female fat mass (g/gBW), n=14-26 and (F) Female fasting serum leptin level (ηg/mL), n=14-25. Alpha diversity was estimated by the (G) (male): Shannon index and (H) (male): Simpson index (n=6-10). Alpha diversity was estimated by the (I) (female): Shannon index and (J) (female): Simpson index i (n=5-13). (A-C) males and (D-F) females from offspring whose mothers were exposed to PM2.5 during pregnancy (PM2.5/FA) or lactation (FA/PM2.5) and filtered air during pregnancy and lactation (FA/FA) as a control group. All mice were 30 weeks of age. Data were expressed as the mean ± SEM. One-way ANOVA was used for the statistical analysis. We used Bonferroni as a post hoc test and a significance of P<0.05. p values: **P<0.01; *P<0.05 (PM2.5/FA vs. FA/FA); &&P<0.01; &P<0.05 (PM2.5/FA vs. FA/PM2.5).
Figure 4
Figure 4
Maternal PM2.5 exposure alters the Linear discriminant analysis (LDA) effect size indicating differences in phyla and genera between (A) FA/FA and PM2.5/FA; (B) FA/FA and FA/PM2.5; (C) PM2.5/FA and FA/PM2.5 groups of males. LDA between (D) FA/FA and PM2.5/FA; (E) FA/FA and FA/PM2.5; (F) PM2.5/FA and FA/PM2.5 groups of females. Offspring mothers were exposed to PM2.5 during pregnancy (PM2.5/FA) or lactation (FA/PM2.5) and filtered air during pregnancy and lactation (FA/FA) as a control group. All mice were 30 weeks of age. The taxa with LDA score > 2 and significance of <0.05 were determined by the Wilcoxon signed-rank test.
Figure 5
Figure 5
Principal coordinate analysis (PCoA) plot with Bray-Curtis dissimilarity. Ordination (PCoA) generated by using the Bray–Curtis dissimilarity metric sampled. Samples are colored according to the group. Male offspring (A, B) Bray-Curtis PCoA ordination. Results revealed that the FA/FA group displayed a spatial separation from PM2.5/FA but not from FA/PM2.5 (PERMANOVA: p = 0.007 and p = 0.46, respectively) (C) PM2.5/FA group showed a spatial separation from FA/PM2.5 (PERMANOVA: p = 0.004). Female offspring (D, E) Bray-Curtis PCoA ordination. Results revealed that the FA/FA group displayed a spatial separation from PM2.5/FA and FA/PM2.5 (PERMANOVA: p = 0.001 and p = 0.030, respectively). (F) PM2.5/FA group showed a spatial separation from FA/PM2.5 (PERMANOVA: p = 0.002).
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