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  1. Fulltext The Risk of Congenital Heart Anomalies Following Prenatal Exposure to Serotonin Reuptake Inhibitors-Is Pharmacogenetics the Key?
    Daud AN, Bergman JE, Kerstjens-Frederikse WS, Groen H, Wilffert B
    Int J Mol Sci, 2016 Aug 13;17(8).
    PMID: 27529241 DOI: 10.3390/ijms17081333
    Serotonin reuptake inhibitors (SRIs) are often prescribed during pregnancy. Previous studies that found an increased risk of congenital anomalies, particularly congenital heart anomalies (CHA), with SRI use during pregnancy have created concern among pregnant women and healthcare professionals about the safety of these drugs. However, subsequent studies have reported conflicting results on the association between CHA and SRI use during pregnancy. These discrepancies in the risk estimates can potentially be explained by genetic differences among exposed individuals. In this review, we explore the potential pharmacogenetic predictors involved in the pharmacokinetics and mechanism of action of SRIs, and their relation to the risk of CHA. In general, the risk is dependent on the maternal concentration of SRIs and the foetal serotonin level/effect, which can be modulated by the alteration in the expression and/or function of the metabolic enzymes, transporter proteins and serotonin receptors involved in the serotonin signalling of the foetal heart development. Pharmacogenetics might be the key to understanding why some children exposed to SRIs develop a congenital heart anomaly and others do not.
    Matched MeSH terms: Prenatal Exposure Delayed Effects/genetics*
  2. Fulltext Prenatal exposure to serotonin reuptake inhibitors and congenital heart anomalies: an exploratory pharmacogenetics study
    Daud ANA, Bergman JEH, Kerstjens-Frederikse WS, van der Vlies P, Hak E, Berger RMF, et al.
    Pharmacogenomics, 2017 Jul;18(10):987-1001.
    PMID: 28639488 DOI: 10.2217/pgs-2017-0036
    AIM: To explore the role of pharmacogenetics in determining the risk of congenital heart anomalies (CHA) with prenatal use of serotonin reuptake inhibitors.

    METHODS: We included 33 case-mother dyads and 2 mother-only (child deceased) cases of CHA in a case-only study. Ten genes important in determining fetal exposure to serotonin reuptake inhibitors were examined: CYP1A2, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC6A4, HTR1A, HTR1B, HTR2A and HTR3B.

    RESULTS: Among the exposed cases, polymorphisms that tended to be associated with an increased risk of CHA were SLC6A4 5-HTTLPR and 5-HTTVNTR, HTR1A rs1364043, HTR1B rs6296 and rs6298 and HTR3B rs1176744, but none reached statistical significance due to our limited sample sizes.

    CONCLUSION: We identified several polymorphisms that might potentially affect the risk of CHA among exposed fetuses, which warrants further investigation.

    Matched MeSH terms: Prenatal Exposure Delayed Effects/genetics
  3. Fulltext Aging Induces Profound Changes in sncRNA in Rat Sperm and These Changes Are Modified by Perinatal Exposure to Environmental Flame Retardant
    Suvorov A, Pilsner JR, Naumov V, Shtratnikova V, Zheludkevich A, Gerasimov E, et al.
    Int J Mol Sci, 2020 Nov 04;21(21).
    PMID: 33158036 DOI: 10.3390/ijms21218252
    Advanced paternal age at fertilization is a risk factor for multiple disorders in offspring and may be linked to age-related epigenetic changes in the father's sperm. An understanding of aging-related epigenetic changes in sperm and environmental factors that modify such changes is needed. Here, we characterize changes in sperm small non-coding RNA (sncRNA) between young pubertal and mature rats. We also analyze the modification of these changes by exposure to environmental xenobiotic 2,2',4,4'-tetrabromodiphenyl ether (BDE-47). sncRNA libraries prepared from epididymal spermatozoa were sequenced and analyzed using DESeq 2. The distribution of small RNA fractions changed with age, with fractions mapping to rRNA and lncRNA decreasing and fractions mapping to tRNA and miRNA increasing. In total, 249 miRNA, 908 piRNA and 227 tRNA-derived RNA were differentially expressed (twofold change, false discovery rate (FDR) p ≤ 0.05) between age groups in control animals. Differentially expressed miRNA and piRNA were enriched for protein-coding targets involved in development and metabolism, while piRNA were enriched for long terminal repeat (LTR) targets. BDE-47 accelerated age-dependent changes in sncRNA in younger animals, decelerated these changes in older animals and increased the variance in expression of all sncRNA. Our results indicate that the natural aging process has profound effects on sperm sncRNA profiles and this effect may be modified by environmental exposure.
    Matched MeSH terms: Prenatal Exposure Delayed Effects/genetics
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