Maternal Prenatal Stress, Thyroid Function and Neurodevelopment of the Offspring: A Mini Review of the Literature

Fetal brain is extremely plastic and vulnerable to environmental influences that may have long-term impact on health and development of the offspring. Both the Hypothalamic-Pituitary-Adrenal (HPA) and the Hypothalamic-Pituitary-Thyroid (HPT) axes are involved in stress responses, whereas, their final effectors, the Glucocorticoids (GCs) and the Thyroid Hormones (TH s), mediate several fundamental processes involved in neurodevelopment. The effects of these hormones on brain development are found to be time and dose-dependent. Regarding THs, the developing fetus depends on maternal supply of hormones, especially in the first half of pregnancy. It is acknowledged that inadequate or excess concentrations of both GCs and THs can separately cause abnormalities in the neuronal and glial structures and functions, with subsequent detrimental effects on postnatal neurocognitive function. Studies are focused on the direct impact of maternal stress and GC excess on growth and neurodevelopment of the offspring. Of particular interest, as results from recent literature data, is building understanding on how chronic stress and alterations of the HPA axis interacts and influences HPT axis and TH production. Animal studies have shown that increased GC concentrations related to maternal stress, most likely reduce maternal and thus fetal circulating THs, either directly or through modifications in the expression of placental enzymes responsible for regulating hormone levels in fetal microenvironment. The purpose of this review is to provide an update on data regarding maternal stress and its impact on fetal neurodevelopment, giving particular emphasis in the interaction of two axes and the subsequent thyroid dysfunction resulting from such circumstances.

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Long-term Impact of an Early Operated Ventricular Septal Defect (VSD): Mental Health and Development in Children at Early School Age

10.1055/s-0039-1698275 ◽

2019 ◽

Author(s):

Valeska Stonawski ◽

Ariawan Purbojo ◽

Robert Cesnjevar ◽

Gunther Moll ◽

Oiver Kratz ◽

...

Keyword(s):

Mental Health ◽

Ventricular Septal Defect ◽

Septal Defect ◽

School Age ◽

Early School ◽

Health And Development ◽

Early School Age ◽

Long Term Impact

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Prenatal corticosterone exposure programs sex-specific adrenal adaptations in mouse offspring

Journal of Endocrinology ◽

10.1530/joe-16-0417 ◽

2017 ◽

Vol 232 (1) ◽

pp. 37-48 ◽

Cited By ~ 20

Author(s):

J S M Cuffe ◽

E L Turton ◽

L K Akison ◽

H Bielefeldt-Ohmann ◽

K M Moritz

Keyword(s):

Maternal Stress ◽

Female Offspring ◽

Male Offspring ◽

Adrenal Weight ◽

Zona Fasciculata ◽

Foetal Development ◽

Plaque Deposition ◽

Acth Receptor ◽

Long Term Impact

Maternal stress can impair foetal development and program sex-specific disease outcomes in offspring through the actions of maternally produced glucocorticoids, predominantly corticosterone (Cort) in rodents. We have demonstrated in mice that male but not female offspring prenatally exposed to Cort (33 µg/kg/h for 60 h beginning at E12.5) develop cardiovascular/renal dysfunction at 12 months. At 6 months of age, renal function was normal but male offspring had increased plasma aldosterone concentrations, suggesting that altered adrenal function may precede disease. This study investigated the long-term impact of prenatal exposure to Cort on adrenal growth, morphology and steroidogenic capacity as well as plasma Cort concentrations in offspring at postnatal day 30 (PN30), 6 months and 12 months of age. Prenatal Cort exposure decreased adrenal volume, particularly of the zona fasciculata, in male offspring at PN30 but increased both relative and absolute adrenal weight at 6 months of age. By 12 months of age, male Cort-exposed offspring had reduced absolute adrenal weight in association with increased adrenal plaque deposition (lipogenic pigmentation). Plasma Cort concentrations were elevated in male 6-month offspring but not at other ages. mRNA expression of Mc2r (ACTH receptor) was increased in males at PN30, and Cyp11a1 expression was decreased at 6 and 12 months of age. There were no changes in the adrenals of female Cort-exposed offspring. This study demonstrates that prenatal Cort exposure induces offspring adrenal gland dysfunction in an age- and sex-specific manner, which may contribute to long-term programmed disease in male offspring after maternal stress.

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The Effects of Maternal Anxiety or Stress During Pregnancy on The Fetus and The Long-Term Development of The Child

Nutrition and Health ◽

10.1177/026010600701900207 ◽

2007 ◽

Vol 19 (1-2) ◽

pp. 61-62 ◽

Cited By ~ 4

Author(s):

Vivette Glover

Keyword(s):

Circadian Rhythm ◽

Cognitive Development ◽

Negative Feedback ◽

Prospective Studies ◽

Prenatal Stress ◽

Maternal Stress ◽

Fetal Brain ◽

Independent Evidence ◽

Objective Evidence ◽

Maternal Prenatal Stress

There is evidence from several prospective studies that stress during pregnancy can affect the behavioural, emotional and cognitive development of the fetus and the child. Animal models suggest that this may be mediated via the HPA axis. Interventions to reduce stress in pregnant women are now a priority. Large prospective studies are providing increasing independent evidence that maternal stress/anxiety during pregnancy can affect fetal brain development, having adverse effects on the child's emotional, behavioural and cognitive development. It is suggested that the function of fetal programming is linked with a predictive adaptive response. Environmental influences on the mother are preparing the child in her womb for the external environment it is likely to inhabit. This is different from the genetic changes and mutations which will be effective for many generations. These affect circadian rhythm including sleep habit, and other aspects including laterality and sexuality. Their seriousness is now well enough established to feature in an American Child Health strategic plan 2005–10. Animal studies have provided a basis for human studies. Antenatal maternal stress in rats leads to anxiety in the offspring. It can alter laterality – right-handedness etc – and sexuality, and disrupt the circadian rhythm including sleep pattern. Prenatal stress reduces the animal's later negative feedback, the calming effect of Cortisol, by reducing the Cortisol receptors in the hippocampus. In monkeys likewise, maternal prenatal stress leaves the offspring with a lower attention span and more anxiety. There are greater Cortisol responses, and imaging also reveals more dopamine receptors to be affected by that stress neurotransmitter. So there is objective evidence of mammalian prenatal stress effects on offspring. In a group of anxious mothers, a simple arithmetic exercise met with a rise in fetal heart-beat, showing that maternal stress clearly affects the fetus. Dr Glover's human research has made use of the ALSPAC community study program. The strongest effects discerned of maternal prenatal stress on the offspring were on behavioural and emotional problems. The strength of effect was stronger from stress at 32 weeks prenatally than 18 weeks, and resulted in double the levels of the offspring's hyperactivity, and emotional and conduct disorders. The children of anxious mothers in late pregnancy had high waking level of Cortisol. In a separate study her group has shown that prenatal stress can affect the child's cognitive development also. In this study it was stress due to relationship problems with the partner, particularly emotional cruelty and separation, which had the largest effect on the child. Studies show that stress acts on the hypothalamus to produce corticotrophin releasing hormone, which in turn acts on the pituitary gland to produce adreno-corticotrophic hormone. This stimulates the adrenal gland to secrete Cortisol for negative feedback to the hippocampus to stabilise the system. Yet both maternal and fetal Cortisol are a positive stimulus on placental CRH. These results suggest the importance of detecting and treating affective disorder and relationship stress during pregnancy, both for the direct benefit to the mother herself, and particularly to help reduce later development of behavioural and other problems in children.

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The lingering impact of stress: brief acute glucocorticoid exposure has sustained, dose-dependent effects on reproduction

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2018.0722 ◽

2018 ◽

Vol 285 (1882) ◽

pp. 20180722 ◽

Cited By ~ 19

Author(s):

Maren N. Vitousek ◽

Conor C. Taff ◽

Daniel R. Ardia ◽

Jocelyn M. Stedman ◽

Cedric Zimmer ◽

...

Keyword(s):

Stress Responses ◽

Acute Stress ◽

Reproductive Period ◽

Stress Effects ◽

Acute Stress Response ◽

Novel Method ◽

Stress Susceptibility ◽

Short Time ◽

Dose Dependent

Acutely stressful experiences can have profound and persistent effects on phenotype. Across taxa, individuals differ remarkably in their susceptibility to stress. However, the mechanistic causes of enduring stress effects, and of individual differences in stress susceptibility, are poorly understood. Here, we tested whether brief, acute increases in glucocorticoid hormones have persistent effects on phenotype, and whether effects differ according to the magnitude or duration of elevation. We used a novel method to non-invasively manipulate hormone levels on short time scales: the application of corticosterone gel to a model egg secured in the nest. Free-living female tree swallows ( Tachycineta bicolor ) exposed to several brief corticosterone increases during incubation showed dose-dependent differences in behaviour throughout the reproductive period. Birds receiving treatments that simulated higher or longer acute stress responses later provisioned larger broods at lower rates; the resulting offspring were smaller in size. Treatment did not influence female body condition, oxidative stress, reproductive success or inter-annual survival, but exposed females maintained higher baseline corticosterone after treatments ceased. Overall, these results indicate that brief, acute elevations in glucocorticoids in adulthood can have long-term consequences. Furthermore, individuals that mount a greater or longer acute stress response may be more likely to experience lingering effects of stress.

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Placental CRH as a Signal of Pregnancy Adversity and Impact on Fetal Neurodevelopment

Frontiers in Endocrinology ◽

10.3389/fendo.2021.714214 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ifigeneia Kassotaki ◽

Georgios Valsamakis ◽

George Mastorakos ◽

Dimitris K. Grammatopoulos

Keyword(s):

Hpa Axis ◽

Stress Responses ◽

Stress Hormones ◽

Fetal Brain ◽

Regulatory System ◽

Genes Encoding ◽

Neuroprotective Actions ◽

As Stress ◽

G Protein Coupled

Early life is a period of considerable plasticity and vulnerability and insults during that period can disrupt the homeostatic equilibrium of the developing organism, resulting in adverse developmental programming and enhanced susceptibility to disease. Fetal exposure to prenatal stress can impede optimum brain development and deranged mother’s hypothalamic–pituitary–adrenal axis (HPA axis) stress responses can alter the neurodevelopmental trajectories of the offspring. Corticotropin-releasing hormone (CRH) and glucocorticoids, regulate fetal neurogenesis and while CRH exerts neuroprotective actions, increased levels of stress hormones have been associated with fetal brain structural alterations such as reduced cortical volume, impoverishment of neuronal density in the limbic brain areas and alterations in neuronal circuitry, synaptic plasticity, neurotransmission and G-protein coupled receptor (GPCR) signalling. Emerging evidence highlight the role of epigenetic changes in fetal brain programming, as stress-induced methylation of genes encoding molecules that are implicated in HPA axis and major neurodevelopmental processes. These serve as molecular memories and have been associated with long term modifications of the offspring’s stress regulatory system and increased susceptibility to psychosomatic disorders later in life. This review summarises our current understanding on the roles of CRH and other mediators of stress responses on fetal neurodevelopment.

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Crisis Phones - Suicide Prevention Versus Suggestion/Contagion Effects

Crisis ◽

10.1027/0227-5910/a000313 ◽

2015 ◽

Vol 36 (3) ◽

pp. 220-224 ◽

Cited By ~ 3

Author(s):

Steven Stack

Keyword(s):

Suicide Prevention ◽

Contagion Effects ◽

Long Term Impact

Abstract. Background: There has been no systematic work on the short- or long-term impact of the installation of crisis phones on suicides from bridges. The present study addresses this issue. Method: Data refer to 219 suicides from 1954 through 2013 on the Skyway Bridge in St. Petersburg, Florida. Six crisis phones with signs were installed in July 1999. Results: In the first decade after installation, the phones were used by 27 suicidal persons and credited with preventing 26 or 2.6 suicides a year. However, the net suicide count increased from 48 in the 13 years before installation of phones to 106 the following 13 years or by 4.5 additional suicides/year (t =3.512, p < .001). Conclusion: Although the phones prevented some suicides, there was a net increase after installation. The findings are interpreted with reference to suggestion/contagion effects including the emergence of a controversial bridge suicide blog.

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