prenatally exposed to methylmercury

Overview

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Key numbers

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Methods Associations between levels of oxidized PUFA metabolites (oxylipins) in placental tissue (N = 12) or cord
blood plasma (N = 39) and postnatal neurodevelopment in children were evaluated at two levels of prenatal mercury
1.4–6.6 µg/L and 20–66 µg/L, respectively. Oxylipins were measured using liquid chromatography mass spectrometry.
(1). Near 5% of the inorganic mercury forms deposited in Interestingly, an interaction between mercury expo-
has established a Reference Dose (RfD) of 0.1 µg/kg body ily affect inflammatory and vascular mechanisms, with
tified 58 µg/L of MeHg in cord blood as a benchmark metabolites with resolution of inflammation properties.
anti-inflammatory and neuroprotective agents (36, 37) arbitrarily categorized as “low” (T-Hg: 1.4 to 6.6 µg/L) or
and may protect the developing brain against genetic or “moderate” (T-Hg: 20 to 66 µg/L). Sample details for sex
environmental insults that would otherwise cause cogni- and T-Hg levels are listed in Supplementary Table 1. The
Table 1 Characteristics of the participating women and their newborns in the study groups of the INMA Project, Valencia
T-Hg (µg/L) 4.3 (2.7–5.9) 23.5 (20.0-27.5)* 1.4 (1.4-3.0) 42.0 (40.0–51.0)**
Data are shown as median (IQR) or number (%). N.D., not determined. Statistics: Mann Whitney test or Chi square test, * p < 0.01, ** p < 0.001 compared to low T-Hg
Cortical brain tissue samples were collected from were homogenized in 0.1% ammonium acetate. Then,
UB-BJ-02 at a dose of 5 mg/Kg or with vehicle (N = 5 per were spiked with internal standards and 3,5-di-tert-4-bu-
taining 1.8% (2-hydroxypropyl)-β-cyclodextrin (vehicle). methanol (0.1% formic acid), centrifugation, and dilution
analyzed using the Proteasome-Glo™ Assay Systems (Pro- detection (LOD), which were 0.7 nmol/mg of tissue in
to the supernatants of placenta lysates to measure chy- samples. Limits of quantification (LOQ) were 2.2 nmol/
Epigenetic changes of histone acetylation and meth- not quantifiable, a value of LOQ x 0.5 was assigned. Oxy-
methods. Tissue homogenates were assayed for global tary Table 3. Results for each pair of fetal and maternal
EpiQuik™ Global Tri-Methyl Histone H3K27 Quantifica- tile range (IQR) for continuous variables, and frequen-
as ß coefficients, 95% confidence intervals (CI) and their a significant 16% increase in H3 trimethylation at lysine
zymatic activity of the proteasome (N = 6 per group). B Levels of trimeth-
placental tissue (N = 6 per group); the boxed graph below shows levels of DiHET isomers with two-way ANOVA statistics. B Levels of 9 oxylipins detected
in cord blood plasma (N = 19–20 per group); the boxed graph below shows levels of 19,20-DiHDPA analyzed using Student’s t -test. Statistics: * p < 0.01;
(Supplementary Table 4). between the Bayley mental scale and several EET and
and Toddler Development at 14 months of age in placental tissue donors (N = 6 per group). B Bayley Scales of Infant and Toddler Development in cord
blood plasma donors (N = 16–18 per group). C McCarthy Scales of Children’s Abilities scores at 5 years of age in cord blood plasma donors (N = 8–17 per
scale and prostaglandin F2α (PGF2α), as well as the anti- mentary Table 7. In the low mercury group, negative cor-
numerical data in Supplementary Table 6. Several DiHET erate mercury exposure group showed positive correla-
14 months of age for low and for moderate mercury group (N = 6 per group). B Correlations between oxylipin levels in cord blood plasma and Bayley
scale scores for the low mercury group (N = 16) and moderate mercury group (N = 18). C Correlations between oxylipin levels in cord blood plasma and
McCarthy scale scores at 5 years of age for the low mercury group (N = 8) and moderate mercury group (N = 17). Statistics: * p < 0.05, ** p < 0.01. The heat
with placental oxylipin level are shown in Table 2. All four correlations with placental oxylipins, as shown in Supple-
EET isomers analyzed showed borderline significance mentary Table 8. The analysis showed very strong posi-
Table 2 Association between Bayley scales at 14 months of age and 17 oxylipins detected in fetal and maternal placental tissue pairs
for all children (N = 12)
are shown in Table 3. Positive association between several the changes observed in oxylipin dynamics was examined
the mental scale, which did not reach significance in the cury exposure groups (Table 1). Furthermore, there was a
oxylipin profile and the psychomotor scale were detected levels (Spearman rho = 0.355, p = 0.040, N = 34), but not
lipins is shown in Table 4 and Supplementary Table 9 A ing, for cadmium and lead.
numerical, and working memory scales (Table 4). A mar- tions of each of the nine oxylipins detected in cord blood
motor scale. TXB2 was also associated with the percep- shown in Supplementary Table 10, alongside with that

Methods (brief)

1.4–6.6 µg/L and 20–66 µg/L, respectively. Oxylipins were measured using liquid chromatography mass spectrometry.
in samples from the moderate exposure group. Additionally, the brain oxylipin profile of mice treated with an AA
Keywords Oxylipins, Polyunsaturated fatty acids, Methylmercury, Human perinatal samples, Fetal neuroprotection,
and may protect the developing brain against genetic or “moderate” (T-Hg: 20 to 66 µg/L). Sample details for sex
Human samples of placenta and cord blood described elsewhere (30, 47). In brief, the BSID includes
The use of human samples and all the procedures of the the Mental scale (163 items) and the Psychomotor scale
Tissue samples of placenta (pairs of fetal and mater- Brain tissue of mice treated with a soluble epoxide
cord blood from all donors had previously been analyzed The use of mouse tissue samples and animal procedures
Cortical brain tissue samples were collected from were homogenized in 0.1% ammonium acetate. Then,
female and male WT and 5XFAD mice treated with the 200 µL of supernatant from tissues or plasma samples
taining 1.8% (2-hydroxypropyl)-β-cyclodextrin (vehicle). methanol (0.1% formic acid), centrifugation, and dilution
placental tissue samples. 2. However, some oxylipins could not be determined
analyzed using the Proteasome-Glo™ Assay Systems (Pro- detection (LOD), which were 0.7 nmol/mg of tissue in
mega, USA). Specific luminogenic substrates were added placenta and mouse brain samples and 0.04 nM in plasma
to the supernatants of placenta lysates to measure chy- samples. Limits of quantification (LOQ) were 2.2 nmol/
motrypsin-like, trypsin-like, and caspase-like activities. mg and 0.13 nM for tissue and plasma samples, respec-
Epigenetic changes of histone acetylation and meth- not quantifiable, a value of LOQ x 0.5 was assigned. Oxy-
Farmingdale, NY, USA), respectively. Histone methyla- Placental and umbilical cord blood samples were ana-

Implications

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Update history

The five most recent substantive edits to this page, classified major (evidence or structure moved), correction (a published value or statement was wrong and has been fixed), or minor (narrative rewritten without changing the underlying evidence). Each description is derived from what the edit did to this page; the linked commit is the authoritative record, routine regeneration passes are excluded, and the full version history lives in git. When DOI minting comes online (see schema docs), each entry below will also link to a version-pinned DataCite DOI.

Commit	Date	Change	Description
b01ec52c	2026-08-04	major	2 sections added
d49e450f	2026-08-03	major	5 sections added; narrative text revised