The Thyroidectomized Pregnant Rat — An Animal Model to Study Fetal Effects of Maternal Hypothyroidism

Porterfield, Susan P.; Hendrich, C. E.

doi:10.1007/978-1-4684-5973-9_5

Cited by 17 publications

(33 citation statements)

References 15 publications

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“…Observations in humans and animal models are consistent with the hypothesis that maternal thyroid hormone regulates early fetal brain development (Porterfield & Hendrich 1991, Morreale de Escobar et al 1997, Pickard et al 1997, Sinha et al 1997. For example, children born to hypothyroxinemic mothers in certain iodine deficiency endemias -though themselves clinically euthyroiddisplay an increased incidence of neurologic disorders, ranging from subclinical deficits in cognitive and motor function to overt neurologic cretinism (Connolly & Pharoah 1989).…”

Section: Introductionsupporting

confidence: 65%

“…Studies in the rat have shown that maternal thyroidectomy impairs fetal somatic and brain growth (Morreale de Escobar et al 1985, Bonet & Herrera 1988, Porterfield & Hendrich 1991, Pickard et al 1993. Such deficits are corrected following the onset of fetal thyroid function in a hypothyroxinemic rat dam model, but sensitive markers of brain cell maturation -such as ornithine decarboxylase and neurotransmitter metabolic enzymes -remain abnormal in postnatal life (Pickard et al 1993, Evans et al 1999.…”

Section: Introductionmentioning

confidence: 99%

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Maternal hypothyroxinemia influences glucose transporter expression in fetal brain and placenta

Pickard¹,

Sinha²,

Ogilvie³

et al. 1999

Journal of Endocrinology

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The influence of maternal hypothyroxinemia on the expression of the glucose transporters, GLUT1 and GLUT3, in rat fetal brain and placenta was investigated. Fetal growth was retarded in hypothyroxinemic pregnancies, but only before the onset of fetal thyroid hormone synthesis. Placental weights were normal, but placental total protein concentration was reduced at 19 days gestation (dg). Immunoblotting revealed a decreased abundance of GLUT1 in placental microsomes at 16 dg, whereas GLUT3 was increased. Fetal serum glucose levels were reduced at 16 dg. In fetal brain, the concentration of microsomal protein was deficient at 16 dg and the abundance of parenchymal forms of GLUT1 was further depressed, whereas GLUT3 was unaffected. Northern hybridization analysis demonstrated normal GLUT1 mRNA levels in placenta and fetal brain.In conclusion, maternal hypothyroxinemia results in fetal growth retardation and impaired brain development before the onset of fetal thyroid function. Glucose uptake in fetal brain parenchyma may be compromised directly, due to deficient GLUT1 expression in this tissue, and indirectly, as a result of reduced placental GLUT1 expression. Though corrected by the onset of fetal thyroid hormone synthesis, these deficits are present during the critical period of neuroblast proliferation and may contribute to long term changes in brain development and function seen in this model and in the progeny of hypothyroxinemic women.

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Section: Introductionsupporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Maternal hypothyroxinemia influences glucose transporter expression in fetal brain and placenta

Pickard¹,

Sinha²,

Ogilvie³

et al. 1999

Journal of Endocrinology

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“…59,60 Maternal glucocorticoid 61,62 and thyroid 63 hormones can cross the blood placental barrier and are essential for normal fetal neurodevelopment. 64,65 However, in humans, exposure of the fetus to excess glucocorticoids can have detrimental effects on fetal brain development 64,66 and hypothyroidism during pregnancy is associated with impaired cognitive and motor function in children.…”

mentioning

confidence: 99%

The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia

et al. 2005

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Maternal infections with bacterial or viral agents during pregnancy are associated with an increased incidence of schizophrenia in the offspring at adulthood although little is known about the mechanism by which maternal infection might affect fetal neurodevelopment. Exposure of pregnant rodents to the bacterial endotoxin, lipopolysaccharide (LPS), results in behavioral deficits in the adult offspring that are relevant to schizophrenia. It is however unknown whether these effects are due to the direct action of the inflammatory stimulus on the developing fetus, or due to secondary immune mediators (cytokines) activated at maternal/ fetal sites. In this study we sought to elucidate the site of action of LPS, following a single intraperitoneal (i.p.) injection, in pregnant rats at gestation day 18. Animals received 5 lCi of iodinated LPS ( 125 I-LPS) and its distribution was assessed in maternal/fetal tissues (1-8 h). In addition, induction of the inflammatory cytokines, TNF-a, IL-1b and IL-6, was measured in maternal/fetal tissues following maternal LPS challenge (0.05 mg/kg, i.p.) (2-8 h). 125I-LPS was detected in maternal tissues and placenta, but not the fetus. This distribution was accompanied by significant increases in TNF-a, IL-1b and IL-6 in maternal plasma and placenta, but not in fetal liver or brain. A significant increase in IL-1b was however detected in fetal plasma, possibly due to transfer from the maternal circulation or placenta. Collectively, these data suggest that effects of maternal LPS exposure on the developing fetal brain are not mediated by the direct action of LPS, but via indirect actions at the level of the maternal circulation or placenta.

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“…In rats, it can be shown that when maternal thyroid hormone levels are low, fetal brain hormone levels are likewise low (30). Such a maternal hormone deficiency in rats results in increased fetal and neonatal mortality, decreased pup size at birth, delayed brain biochemical maturation, delayed cell acquisition, and delayed neuronal maturation (31). While as adults the thyroid function of these progenies is relatively normal, they show learning and memory deficiencies and are hyperactive (29).…”

Section: Maternal Hypothyroidism During Pregnancymentioning

confidence: 99%

“…Furthermore, in mice and rats, both insults result in delayed acquisition of auditory startle, cliff avoidance, negative geotaxis, and air-righting (62,67). Rodents show a decreased birth weight and litter size after both exposures (31)(32)(33) …”

Section: Neurological Effects Of the Toxinsmentioning

confidence: 99%

Vulnerability of the developing brain to thyroid abnormalities: environmental insults to the thyroid system.

Porterfield

1994

Environ Health Perspect

160

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Neurologic development follows orderly patterns that can be severely disturbed when thyroid hormones are deficient or excessive. Should this occur at appropriate development periods, irreversible neurologic damage can result. The nature of the deficits depends upon the specific development period and the severity of the thyroid disturbance. PCBs and dioxins are structurally similar to the thyroid hormones. Their binding characteristics are similar to those of thyroid hormones and all three groups bind to the cytosolic Ah receptor, the thyroid hormone receptor and the serum thryoid hormone binding protein transthyretin. Depending upon the dose of toxin and the congener used, the toxins either decrease or minic the biological action of the thyroid hormones. Either effect, if occurring during brain development, can have disastrous consequences. Children and animals exposed to PCBs or dioxins in utero and/or as infants can exhibit varying degrees of behavioral disorders. These disorders resemble those seen in children exposed to thyroid hormone deficiencies in utero and/or in infancy. The mechanism of developmental neurotoxicity of PCBs and dioxins is not known but data suggest it could be partially or entirely mediated by alterations in availability and action of thyroid hormones during neurological development. It is possible that transient exposure of the mother to doses of toxins presently considered nontoxic to the mother could have an impact upon fetal or perinatal neurological development. If the toxins act via their effect on thyroid hormone action, it is possible that doses of toxins that would normally not alter fetal development, could become deleterious if superimposed on a pre-existing maternal/or fetal thyroid disorder. Environ Health Perspect 102(Suppl 2): 125-130 (1994).

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The Thyroidectomized Pregnant Rat — An Animal Model to Study Fetal Effects of Maternal Hypothyroidism

Cited by 17 publications

References 15 publications

Maternal hypothyroxinemia influences glucose transporter expression in fetal brain and placenta

Maternal hypothyroxinemia influences glucose transporter expression in fetal brain and placenta

The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia

Vulnerability of the developing brain to thyroid abnormalities: environmental insults to the thyroid system.

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