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•Fluoride may disrupt thyroid function in pregnant women.•Fluoride exposure was associated with alterations in maternal thyroid hormone levels.•Urinary fluoride was associated with ...significantly higher TSH among those pregnant with females.•Adjustment for maternal iodine status did not change the results.
Fluoride exposure may increase the risk of hypothyroidism, but results from previous studies are inconsistent at low-level fluoride exposure (i.e., ≤0.7 mg/L). Human studies of fluoride and thyroid hormone levels in pregnancy are scarce.
We examined associations between fluoride exposure and maternal thyroid hormone levels in a Canadian pregnancy cohort, with consideration for fetal sex-specific effects.
We measured fluoride concentrations in drinking water and spot urine samples collected during each trimester from 1876 pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) study. We also measured maternal thyroid stimulating hormone (TSH), free thyroxine (FT4), and total thyroxine (TT4) levels during the first trimester of pregnancy. We used linear and non-linear regression models to estimate associations between fluoride exposure and levels of TSH, FT4, and TT4. We explored effect modification by fetal sex and considered maternal iodine status as a potential confounder.
A 1 mg/L increase in urinary fluoride was associated with a 0.30 (95 %CI: 0.08, 0.51) logarithmic unit (i.e., 35.0 %) increase in TSH among women pregnant with females, but not males (B = 0.02; 95 %CI: −0.16, 0.19). Relative to women with urinary fluoride concentrations in the first quartile (0.05–0.32 mg/L), those with levels in the third quartile (0.49–0.75 mg/L) had higher FT4 and TT4 (i.e., inverted J-shaped associations), but the association was not statistically significant after adjustment for covariates (p = 0.06). Water fluoride concentration showed a U-shaped association with maternal FT4, whereby women with water fluoride concentrations in the second (0.13–0.52 mg/L) and third (0.52–0.62 mg/L) quartiles had significantly lower FT4 compared to those with levels in the first quartile (0.04–0.13 mg/L). Adjustment for maternal iodine status did not change the results.
Fluoride exposure was associated with alterations in maternal thyroid hormone levels, the magnitude of which appeared to vary by fetal sex. Given the importance of maternal thyroid hormones for fetal neurodevelopment, replication of findings is warranted.
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•This is the first study to examine associations between prenatal fluoride exposure and disruptions to visual acuity and cardiac autonomic function in infants.•In this Canadian ...pregnancy cohort, prenatal fluoride exposure was linked to poorer visual acuity.•Prenatal fluoride exposure was linked to lower heart rate variability (root mean square of successive differences)•Results suggest that prenatal fluoride exposure may be associated with poorer central and peripheral markers of nervous system functioning in infant offspring.
Prenatal fluoride exposure can have adverse effects on children’s development; however, associations with visual and cardiac autonomic nervous system functioning are unknown. We examined associations between prenatal fluoride exposure and visual acuity and heart rate variability (HRV) in 6-month-old infants.
We used data from Canadian mother-infant pairs participating in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort. We estimated prenatal fluoride exposure using: i) fluoride concentration in drinking water (mg/L), ii) maternal urinary fluoride adjusted for specific gravity (MUFSG; mg/L) and averaged across pregnancy, and iii) maternal fluoride intake (µg/kg/day) from consumption of water, tea, and coffee, adjusted for maternal body weight (kg). We used multivariable linear regression to examine associations between each measure of fluoride exposure and Teller Acuity Card visual acuity scores (n = 435) and assessed HRV (n = 400) using two measures: root mean square of successive differences (RMSSD) and the standard deviation of N-N intervals (SDNN) measured at 6-months of age.
Median (IQR) values for water fluoride, MUFSG, and daily fluoride intake were 0.20 (IQR: 0.13–0.56) mg/L; 0.44 (0.28–0.70) mg/L and 4.82 (2.58–10.83) µg/kg/day, respectively. After adjustment for confounding variables, water fluoride concentration was associated with poorer infant visual acuity (B = -1.51; 95 % CI: −2.14,-0.88) and HRV as indicated by lower RMSSD (B = -1.60; 95 % CI: −2.74,-0.46) but not SDNN. Maternal fluoride intake was also associated with poorer visual acuity (B = -0.82; 95 % CI: −1.35,-0.29) and lower RMSSD (B = -1.22; 95 % CI: −2.15,-0.30). No significant associations were observed between MUFSG and visual acuity or HRV.
Fluoride in drinking water was associated with reduced visual acuity and alterations in cardiac autonomic function in infancy, adding to the growing body of evidence suggesting fluoride's developmental neurotoxicity.
In animal studies, the combination of in utero fluoride exposure and low iodine has greater negative effects on offspring learning and memory than either alone, but this has not been studied in ...children. We evaluated whether the maternal urinary iodine concentration (MUIC) modifies the association between maternal urinary fluoride (MUF) and boys' and girls' intelligence. We used data from 366 mother-child dyads in the Maternal-Infant Research on Environmental Chemicals Study. We corrected trimester-specific MUF and MUIC for creatinine, and averaged them to yield our exposure variables (MUF
, mg/g; MUIC
, µg/g). We assessed children's full-scale intelligence (FSIQ) at 3 to 4 years. Using multiple linear regression, we estimated a three-way interaction between MUF
, MUIC
, and child sex on FSIQ, controlling for covariates. The MUIC
by MUF
interaction was significant for boys (
= 0.042), but not girls (
= 0.190). For boys whose mothers had low iodine, a 0.5 mg/g increase in MUF
was associated with a 4.65-point lower FSIQ score (95% CI: -7.67, -1.62). For boys whose mothers had adequate iodine, a 0.5 mg/g increase in MUF
was associated with a 2.95-point lower FSIQ score (95% CI: -4.77, -1.13). These results suggest adequate iodine intake during pregnancy may minimize fluoride's neurotoxicity in boys.
While molecular analyses have provided insight into the phylogeny of ciliates, the few studies assessing intraspecific variation have largely relied on just a single locus e.g., nuclear small subunit ...rDNA (nSSU-rDNA) or mitochondrial cytochrome oxidase I. In this study, we characterize the diversity of several nuclear protein-coding genes plus both nSSU-rDNA and mitochondrial small subunit rDNA (mtSSU-rDNA) of five isolates of the ciliate morphospecies
Chilodonella uncinata
. Although these isolates have nearly identical nSSU-rDNA sequences, they differ by up to 8.0% in mtSSU-rDNA. Comparative analyses of all loci, including β-tubulin paralogs, indicate a lack of recombination between strains, demonstrating that the morphospecies
C. uncinata
consists of multiple cryptic species. Further, there is considerable variation in substitution rates among loci as some protein-coding domains are nearly identical between isolates, while others differ by up to 13.2% at the amino acid level. Combining insights on macronuclear variation among isolates, the focus of this study, with published data from the micronucleus of two of these isolates, indicates that
C. uncinata
lineages are able to maintain both highly divergent and highly conserved genes within a rapidly evolving germline genome.
Fluoride exposure >1.5 mg/L from water has been associated with adverse pregnancy and birth outcomes. Little is known, however, about the effect of fluoride at levels consistent with water ...fluoridation (i.e., 0.7 mg/L) on pregnancy and birth outcomes. We examined the relationship between maternal fluoride exposure, fertility, and birth outcomes in a Canadian pregnancy cohort living in areas where municipal drinking water fluoride concentrations ranged from 0.04 to 0.87 mg/L.
Using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) study, we estimated fluoride exposure during pregnancy using three different metrics: (1) maternal urinary fluoride concentrations standardized for specific gravity (MUFSG) and averaged across all three trimesters (N = 1566), (2) water fluoride concentration (N = 1370), and (3) fluoride intake based on self-reported consumption of water, coffee, and tea, adjusted for body weight (N = 1192). Data on fertility, birth weight, gestational age, preterm birth, and small-for-gestational age (SGA) were assessed. We used multiple linear regression to examine associations between fluoride exposure, birth weight and gestational age, and logistic regression to examine associations with fertility, preterm birth, and SGA, adjusted for relevant covariates.
Median (IQR) MUFSG was 0.50 (0.33–0.76) mg/L, median water fluoride was 0.52 (0.17–0.64) mg/L, and median fluoride intake was 0.008 (0.003–0.013) mg/kg/day. MUFSG, water fluoride concentrations, and fluoride intake were not significantly associated with fertility, birth weight, gestational age, preterm birth, or SGA. Fetal sex did not modify any of the associations.
Fluoride exposure during pregnancy was not associated with fertility or birth outcomes in this Canadian cohort.
The multiple species concepts currently in use by the scientific community (e.g. Morphological, Biological, Phylogenetic) are united in that they all aim to capture the process of divergence between ...populations. For example, the Biological Species Concept defines a species as a natural group of organisms that is reproductively isolated from other such groups. Here we synthesize nearly a century of research on the ciliate genus Paramecium that highlights the shortcomings of our prevailing notions on the nature of species. In this lineage, there is discordance between morphology, mating behavior, and genetics, features assumed to be correlated, at least after sufficient time has passed, under all species concepts. Intriguingly, epigenetic phenomena are well documented in ciliates where they influence features such as germline/soma differentiation and mating type determination. Consequently, we hypothesize that divergence within ciliate populations is due to a dynamic interaction between genetic and epigenetic factors. The growing list of examples of epigenetic phenomena that potentially impact speciation (i.e. by influencing the dynamics of sex chromosomes, fate of hybrids, zygotic drive and genomic conflicts) suggests that interactions between genetics and epigenetics may also drive divergence in other eukaryotic lineages.
Histone variants H2A.Z and H3.3 are epigenetic regulators of memory, but roles of other variants are not well characterized. macroH2A (mH2A) is a structurally unique histone that contains a globular ...macrodomain connected to the histone region by an unstructured linker. Here we assessed if mH2A regulates memory and if this role varies for the two mH2A-encoding genes, H2afy (mH2A1) and H2afy2 (mH2A2). We show that fear memory is impaired in mH2A1, but not in mH2A2-deficient mice, whereas both groups were impaired in a non-aversive spatial memory task. However, impairment was larger for mH2A1- deficient mice, indicating a preferential role for mH2A1 over mH2A2 in memory. Accordingly, mH2A1 depletion in the mouse hippocampus resulted in more extensive transcriptional de-repression compared to mH2A2 depletion. mH2A1-depleted mice failed to induce a normal transcriptional response to fear conditioning, suggesting that mH2A1 depletion impairs memory by altering transcription. Using chromatin immunoprecipitation (ChIP) sequencing, we found that both mH2A proteins are enriched on transcriptionally repressed genes, but only mH2A1 occupancy was dynamically modified during learning, displaying reduced occupancy on upregulated genes after training. These data identify mH2A as a regulator of memory and suggest that mH2A1 supports memory by repressing spurious transcription and promoting learning-induced transcriptional activation.
Mitochondrial SSU-rDNA has been used recently to infer phylogenetic relationships among a few ciliates. Here, this locus is compared with nuclear SSU-rDNA for uncovering the deepest nodes in the ...ciliate tree of life using broad taxon sampling. Nuclear and mitochondrial SSU-rDNA reveal the same relationships for nodes well-supported in previously-published nuclear SSU-rDNA studies, although support for many nodes in the mitochondrial SSU-rDNA tree are low. Mitochondrial SSU-rDNA infers a monophyletic Colpodea with high node support only from Bayesian inference, and in the concatenated tree (nuclear plus mitochondrial SSU-rDNA) monophyly of the Colpodea is supported with moderate to high node support from maximum likelihood and Bayesian inference. In the monophyletic Phyllopharyngea, the Suctoria is inferred to be sister to the Cyrtophora in the mitochondrial, nuclear, and concatenated SSU-rDNA trees, with moderate to high node support from maximum likelihood and Bayesian inference. Together, these data point to the power of adding mitochondrial SSU-rDNA as a standard locus for ciliate molecular phylogenetic inferences.
While fluoride can have thyroid-disrupting effects, associations between low-level fluoride exposure and thyroid conditions remain unclear, especially during pregnancy when insufficient thyroid ...hormones can adversely impact offspring development.
We evaluated associations between fluoride exposure and hypothyroidism in a Canadian pregnancy cohort.
We measured fluoride concentrations in drinking water and three dilution-corrected urine samples and estimated fluoride intake based on self-reported beverage consumption. We classified women enrolled in the Maternal-Infant Research on Environmental Chemicals Study as euthyroid (n = 1301), subclinical hypothyroid (n = 100) or primary hypothyroid (n = 107) based on their thyroid hormone levels in trimester one. We used multinomial logistic regression to estimate the association between fluoride exposure and classification of either subclinical or primary hypothyroidism and considered maternal thyroid peroxidase antibody (TPOAb) status, a marker of autoimmune hypothyroidism, as an effect modifier. In a subsample of 466 mother-child pairs, we used linear regression to explore the association between maternal hypothyroidism and child Full-Scale IQ (FSIQ) at ages 3-to-4 years and tested for effect modification by child sex.
A 0.5 mg/L increase in drinking water fluoride concentration was associated with a 1.65 (95 % confidence interval CI: 1.04, 2.60) increased odds of primary hypothyroidism. In contrast, we did not find a significant association between urinary fluoride (adjusted odds ratio aOR: 1.00; 95%CI: 0.73, 1.39) or fluoride intake (aOR: 1.25; 95%CI: 0.99, 1.57) and hypothyroidism. Among women with normal TPOAb levels, the risk of primary hypothyroidism increased with both increasing water fluoride and fluoride intake (aOR water fluoride concentration: 2.85; 95%CI: 1.25, 6.50; aOR fluoride intake: 1.75; 95%CI: 1.27, 2.41). Children born to women with primary hypothyroidism had lower FSIQ scores compared to children of euthyroid women, especially among boys (B coefficient: −8.42; 95 % CI: −15.33, −1.50).
Fluoride in drinking water was associated with increased risk of hypothyroidism in pregnant women. Thyroid disruption may contribute to developmental neurotoxicity of fluoride.
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•Fluoride may disrupt thyroid function.•Thyroid dysfunction in pregnancy can adversely impact offspring development.•Fluoride in water increased risk of hypothyroidism in pregnant women.•Boys had lower IQ scores if their mothers were hypothyroid in pregnancy.•Thyroid disruption may contribute to developmental neurotoxicity of fluoride.
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