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Adverse effects of melatonin on rat pups of Wistar-Kyoto dams receiving melatonin supplementation during pregnancy

Singh HJ, Keah LS, Kumar A, Sirajudeen KN

Exp. Toxicol. Pathol., 2012 Nov;64(7-8):751-2.
PMID: 21354772 DOI: 10.1016/j.etp.2011.01.011

This report documents an incidental finding during a study investigating the effects of melatonin supplementation on the development of blood pressure in SHR. Administration of 10 mg/kg/day of melatonin in drinking water during pregnancy to Wistar-Kyoto (WKY) dams caused a loss of more than 50% of the pups by the age of three weeks and 95% by the age of 6 weeks. There was no maternal morbidity or mortality in the two strains or death of any of the SHR pups. No obvious physical defects were present but mean body weight was lower in the surviving WKY rats when compared to that of melatonin supplemented SHR or non-supplemented WKY pups. The reason for the high mortality in WKY pups is uncertain and appears to be strain if not batch specific. There is a need for caution in its use, particularly during pregnancy, and clearly necessitates more detailed studies.

Matched MeSH terms: Prenatal Exposure Delayed Effects/chemically induced*
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/chemically induced*
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/chemically induced*
Fulltext The impacts of intrauterine Bisphenol A exposure on pregnancy and expression of miRNAs related to heart development and diseases in animal model

Rasdi Z, Kamaludin R, Ab Rahim S, Syed Ahmad Fuad SB, Othman MHD, Siran R, et al.

Sci Rep, 2020 Apr 03;10(1):5882.
PMID: 32246001 DOI: 10.1038/s41598-020-62420-1

This study aimed to examine the impact of BPA exposure on pregnancy and foetuses on cardiac tissues and the expression of cardiac microRNAs (miRNAs) related to heart development and diseases. Pregnancy is known to be the "critical windows" in determining the offspring physical and cells development in their life after birth. The increment of the risk of cardiovascular disease (CVD) in a later stage of life has been reported by few studies demonstrated from prenatal exposure of BPA. BPA has been shown to alter miRNAs expression profiles for organ development, regeneration and metabolic functions. These alterations have been associated with the risk of CVDs. However, the associations between pregnancy outcomes and miRNAs expression in cardiac of mother- and foetuses-exposed to BPA are still not entirely explored. In BPA-exposed pregnant rat groups, a significant weight gained was observed in comparison to control (p

Matched MeSH terms: Prenatal Exposure Delayed Effects/chemically induced*
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/chemically induced
The effects of prenatal alcohol exposure on the morphological characteristics of spinal motoneurons

David P, Subramaniam K

Birth Defects Res. Part A Clin. Mol. Teratol., 2009 Sep;85(9):791-9.
PMID: 19452514 DOI: 10.1002/bdra.20593

Clinical studies and research in animals have established that alcohol consumption during pregnancy produces irreversible developmental anomalies. Deficits in fine motor performance are often noted in infants diagnosed with fetal alcohol syndrome. However, the effects of alcohol on the spinal motoneurons have not been examined. In this study, the morphometric alterations in spinal motoneurons were assessed as a result of prenatal alcohol exposure.

Matched MeSH terms: Prenatal Exposure Delayed Effects/chemically induced*
Pre- and postnatal toxicity of diazinon induces disruption of spermatogenetic cell line evidenced by increased testicular marker enzymes activities in rat offspring

Jayachandra S, D'Souza UJ

J Environ Pathol Toxicol Oncol, 2013;32(1):73-90.
PMID: 23758154

The objective of this study was to study the possible reproductive adverse effects of the diazinon on rat offspring exposed in utero and during lactation. Dams were gavaged daily (10, 15, and 30 mg/kg) before mating, during mating, and during pregnancy and lactation in separate groups. Reproductive outcome data of dams were examined. Body weight, testis weight, testicular marker enzyme activities (alkaline phosphatase, acid phosphatase, lactate dehydrogenase, and glucose-6-phosphate dehydrogenase), qualitative and quantitative testicular and epididymal histology, and immunohistochemisty for 3-β-hydroxysteroid dehydrogenase (HSD) were examined in male offspring at puberty and adulthood. The 30-mg/kg dose induced significant adverse effects at both puberty and adulthood in offspring. At puberty the male offspring showed a decrease in testicular weight, degenerative changes, and 3-β-HSD. Moreover, an increase in activity of alkaline and acid phosphatase also was observed. At adulthood, there was a decrease in testicular weight and 3-β-HSD with an increase in the levels of testicular marker enzyme. There was evidence of some adverse reproductive effects in male offspring at the 15-mg/kg dose. Most of the adverse effects were irreversible and were evident at both puberty and adulthood in offspring, although a few parameters reverted back to the normal growth pattern. Hence, diazinon is a reproductive toxicant in male offspring, which caused significant damage to the testes when exposed during prenatal and postnatal life.

Matched MeSH terms: Prenatal Exposure Delayed Effects/chemically induced*