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Analysis of Selenoprotein Expression in Response to Dietary Selenium Deficiency During Pregnancy Indicates Tissue Specific Differential Expression in Mothers and Sex Specific Changes in the Fetus and Offspring.

ABSTRACT: The human selenoproteome is comprised of ~25 genes, which incorporate selenium, in the form of selenocysteine, into their structure. Since it is well known that selenium is important to maternal health and foetal development during pregnancy, this study aimed at defining the impact of selenium deficiency on maternal, placental, foetal and offspring selenoprotein gene expression. Female C57BL/6 mice were randomly allocated to control (>190 ?g/kg) or low selenium (<50 ?g/kg) diets four weeks prior to mating and throughout gestation. At embryonic day (E)18.5, pregnant mice were sacrificed followed by collection of maternal and foetal tissues. A subset of mice littered down, and offspring were monitored from postnatal day (PN) 8, weaned at PN24 and sacrificed at PN180, followed by tissue collection. Following RNA extraction, the expression of 14 selenoproteins was assessed with qPCR in liver, kidneys, muscle and placenta. Selenium deficiency downregulated expression (Ptrt < 0.05) of many selenoproteins in maternal tissues and the placenta. However, foetal selenoprotein expression was upregulated (Ptrt < 0.05) in all tissues, especially the kidneys. This was not reflected at PN180; however, a sexually dimorphic relationship in selenoprotein expression was observed in offspring. This study demonstrates the selenoproteome is sensitive to dietary selenium levels, which may be exacerbated by pregnancy. We concluded that transcriptional regulation of selenoproteins is complex and multifaceted, with expression exhibiting tissue-, age- and sex-specificities.

SUBMITTER: Hofstee P

PROVIDER: S-EPMC7139809 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Analysis of Selenoprotein Expression in Response to Dietary Selenium Deficiency During Pregnancy Indicates Tissue Specific Differential Expression in Mothers and Sex Specific Changes in the Fetus and Offspring.

Hofstee Pierre P Cuffe James S M JSM Perkins Anthony V AV

International journal of molecular sciences 20200323 6

The human selenoproteome is comprised of ~25 genes, which incorporate selenium, in the form of selenocysteine, into their structure. Since it is well known that selenium is important to maternal health and foetal development during pregnancy, this study aimed at defining the impact of selenium deficiency on maternal, placental, foetal and offspring selenoprotein gene expression. Female <i>C57BL/6</i> mice were randomly allocated to control (>190 μg/kg) or low selenium (<50 μg/kg) diets four week ...[more]

PMID: 32210049

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Project description:ImportancePrior studies using large registries have suggested a modest increase in risk for neurodevelopmental diagnoses among children of mothers with immune activation during pregnancy, and such risk may be sex-specific.ObjectiveTo determine whether in utero exposure to SARS-CoV-2 is associated with sex-specific risk for neurodevelopmental disorders up to 18 months after birth, compared with unexposed offspring born during or prior to the COVID-19 pandemic period.Design, setting, and participantsThis retrospective cohort study included the live offspring of all mothers who delivered between January 1 and December 31, 2018 (born and followed up before the COVID-19 pandemic), between March 1 and December 31, 2019 (born before and followed up during the COVID-19 pandemic), and between March 1, 2020, and May 31, 2021 (born and followed up during the COVID-19 pandemic). Offspring were born at any of 8 hospitals across 2 health systems in Massachusetts.ExposuresPolymerase chain reaction evidence of maternal SARS-CoV-2 infection during pregnancy.Main outcomes and measuresElectronic health record documentation of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes corresponding to neurodevelopmental disorders.ResultsThe COVID-19 pandemic cohort included 18 355 live births (9399 boys [51.2%]), including 883 (4.8%) with maternal SARS-CoV-2 positivity during pregnancy. The cohort included 1809 Asian individuals (9.9%), 1635 Black individuals (8.9%), 12 718 White individuals (69.3%), and 1714 individuals (9.3%) who were of other race (American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, more than 1 race); 2617 individuals (14.3%) were of Hispanic ethnicity. Mean maternal age was 33.0 (IQR, 30.0-36.0) years. In adjusted regression models accounting for race, ethnicity, insurance status, hospital type (academic center vs community), maternal age, and preterm status, maternal SARS-CoV-2 positivity was associated with a statistically significant elevation in risk for neurodevelopmental diagnoses at 12 months among male offspring (adjusted OR, 1.94 [95% CI 1.12-3.17]; P = .01) but not female offspring (adjusted OR, 0.89 [95% CI, 0.39-1.76]; P = .77). Similar effects were identified using matched analyses in lieu of regression. At 18 months, more modest effects were observed in male offspring (adjusted OR, 1.42 [95% CI, 0.92-2.11]; P = .10).Conclusions and relevanceIn this cohort study of offspring with SARS-CoV-2 exposure in utero, such exposure was associated with greater magnitude of risk for neurodevelopmental diagnoses among male offspring at 12 months following birth. As with prior studies of maternal infection, substantially larger cohorts and longer follow-up will be required to reliably estimate or refute risk.

Dataset Information

Analysis of Selenoprotein Expression in Response to Dietary Selenium Deficiency During Pregnancy Indicates Tissue Specific Differential Expression in Mothers and Sex Specific Changes in the Fetus and Offspring.

Publications

Analysis of Selenoprotein Expression in Response to Dietary Selenium Deficiency During Pregnancy Indicates Tissue Specific Differential Expression in Mothers and Sex Specific Changes in the Fetus and Offspring.

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