Prenatal stress and glucocorticoid effects on the developing gender-related brainProceedings of Xth International Congress on Hormonal Steroids, Quebec, Canada, 17–21 June 1998.

Reznikov, Alexander; Nosenko, N. D.; Tarasenko, L. V.

doi:10.1016/s0960-0760(98)00151-4

Cited by 58 publications

(9 citation statements)

References 24 publications

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“…In addition, these changes reduced or disrupted established sex-differences by dysmasculinizing male offspring measures of stress responsivity (Mueller and Bale, 2007, 2008). Similar disruptions of sex differences in behavior, morphology, and gene expression profiles have previously been reported in studies utilizing prenatal stress paradigms across multiple species (Ward, 1972; Meisel et al, 1979; Reznikov et al, 1999; Biala et al, 2010) (Kapoor and Matthews, 2005). The organizational/activational hypothesis of brain development suggests that a surge of gonadal hormones organize the brain in a sexually dimorphic manner during the perinatal sensitive period.…”

Section: Introductionsupporting

confidence: 70%

Early Prenatal Stress Epigenetically Programs Dysmasculinization in Second-Generation Offspring via the Paternal Lineage

Morgan¹,

Bale²

2011

J. Neurosci.

297

213

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Studies have linked sex-biased neurodevelopmental disorders, including autism and schizophrenia, with fetal antecedents such as prenatal stress. Further, these outcomes can persist into subsequent generations raising the possibility that aspects of heritability in these diseases involve epigenetic mechanisms. Utilizing a mouse model in which we previously identified a period in early gestation when stress results in dysmasculinized and stress-sensitive male offspring, we have examined programming effects in second-generation offspring of prenatally stressed (F2-S) or control (F2-C) sires. Examination of gene expression patterns during the perinatal sensitive period, when organizational gonadal hormones establish the sexually dimorphic brain, confirmed dysmasculinization in F2-S males where genes important in neurodevelopment showed a female-like pattern. Analyses of the epigenomic miRNA environment detected significant reductions in miR-322, miR-574, and miR-873 in the F2-S male brain, levels that were again more similar to those of control females. Increased expression of a common gene target for these 3 miRNAs, β-glycan, was confirmed in these males. These developmental effects were associated with the transmission of a stress-sensitive phenotype and shortened anogenital distance in adult F2-S males. As confirmation that the miRNA environment is responsive to organizational testosterone, neonatal males administered the aromatase inhibitor formestane exhibited dramatic changes in brain miRNA patterns, suggesting miRNAs may serve a previously unappreciated role in organizing the sexually dimorphic brain. Overall, these data support the existence of a sensitive period of early gestation when epigenetic programming of the male germline can occur, permitting transmission of specific phenotypes into subsequent generations.

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Section: Introductionsupporting

confidence: 70%

Early Prenatal Stress Epigenetically Programs Dysmasculinization in Second-Generation Offspring via the Paternal Lineage

Morgan¹,

Bale²

2011

J. Neurosci.

297

213

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“…For example, Reznikov and coworkers found sexually dimorphic changes in neuronal cell nuclei volumes in the suprachiasmatic nucleus of 10-day-old pups after prenatal stress (Reznikov et al, 1999). In the fetal PVN prenatal stress-induced apoptosis appears to be more pronounced in females than in males (Tobe et al, 2005).…”

Section: Vulnerability and Resilience Towards Early Life Stress: Sex mentioning

confidence: 99%

“…Also, it has been shown that different parameters in the hypothalamus such as cell death and proliferation as well as astrocyte and synaptic markers, respond differentially in males and females following both, prenatal and adult stress exposure (Garcia-Caceres et al, 2010). There is also evidence for sex-specific changes in neurochemical profiles regarding dopaminergic, serotonergic and GABAergic systems in rats and degus in response to early stress (Reznikov et al, 1999; Ziabreva et al, 2003; Jezierski et al, 2006; Barbosa Neto et al, 2012; Leon Rodriguez and Duenas, 2013). …”

Section: Vulnerability and Resilience Towards Early Life Stress: Sex mentioning

confidence: 99%

“…In contrast, the medial prefrontal cortex of unstressed male controls displayed denser catecholaminergic fibers than control females, which decreased after ELS exposure down to the level of female controls. Several other studies revealed that early life adversity reduces pre-existing differences between males and females, which might be interpreted as feminization or masculinization of behavior, brain structure, physiology and gene expression (Reznikov et al, 1999; Bowman et al, 2004; Gue et al, 2004; Mandyam et al, 2008; Zuena et al, 2008; Biala et al, 2011; Bock et al, 2011; Salomon et al, 2011). …”

Section: Vulnerability and Resilience Towards Early Life Stress: Sex mentioning

confidence: 99%

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Perinatal programming of emotional brain circuits: an integrative view from systems to molecules

et al. 2014

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Environmental influences such as perinatal stress have been shown to program the developing organism to adapt brain and behavioral functions to cope with daily life challenges. Evidence is now accumulating that the specific and individual effects of early life adversity on the functional development of brain and behavior emerge as a function of the type, intensity, timing and the duration of the adverse environment, and that early life stress (ELS) is a major risk factor for developing behavioral dysfunctions and mental disorders. Results from clinical as well as experimental studies in animal models support the hypothesis that ELS can induce functional “scars” in prefrontal and limbic brain areas, regions that are essential for emotional control, learning and memory functions. On the other hand, the concept of “stress inoculation” is emerging from more recent research, which revealed positive functional adaptations in response to ELS resulting in resilience against stress and other adversities later in life. Moreover, recent studies indicate that early life experiences and the resulting behavioral consequences can be transmitted to the next generation, leading to a transgenerational cycle of adverse or positive adaptations of brain function and behavior. In this review we propose a unifying view of stress vulnerability and resilience by connecting genetic predisposition and programming sensitivity to the context of experience-expectancy and transgenerational epigenetic traits. The adaptive maturation of stress responsive neural and endocrine systems requires environmental challenges to optimize their functions. Repeated environmental challenges can be viewed within the framework of the match/mismatch hypothesis, the outcome, psychopathology or resilience, depends on the respective predisposition and on the context later in life.

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“…Furthermore, gestational stress or fetal glucocorticoid exposure has severe impact on the structural changes of the hypothalamus, including on the sexually dimorphic nucleus of the POA, anterioventral periventricular nucleus and the suprachiasmatic nucleus in male offspring (Reznikov et al 1999; Rhees et al 1999; Weinstock 2007). In addition, fetal exposure to glucocorticoid receptor agonist, dexamethasone (DEX) leads to reduced plasma testosterone levels and impaired sexual behavior in male offspring (Lalau et al 1990; Ward et al 1994; Holson et al 1995; Page et al 2001; Gerardin et al 2005) as well as delayed pubertal onset in female rodents (Smith and Waddell 2000; Soga et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Maternal dexamethasone exposure during pregnancy in rats disrupts gonadotropin-releasing hormone neuronal development in the offspring

2013

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The migration of gonadotropin-releasing hormone (GnRH) neurons from the olfactory placode to the preoptic area (POA) from embryonic day 13 is important for successful reproduction during adulthood. Whether maternal glucocorticoid exposure alters GnRH neuronal morphology and number in the offspring is unknown. This study determines the effect of maternal dexamethasone (DEX) exposure on enhanced green fluorescent protein (EGFP) driven by GnRH promoter neurons (TG-GnRH) in transgenic rats dual-labelled with GnRH immunofluorescence (IF-GnRH). The TG-GnRH neurons were examined in intact male and female rats at different postnatal ages, as a marker for GnRH promoter activity. Pregnant females were subcutaneously injected with DEX (0.1 mg/kg) or vehicle daily during gestation days 13–20 to examine the number of GnRH neurons in P0 male offspring. The total number of TG-GnRH neurons and TG-GnRH/IF-GnRH neuronal ratio increased from P0 and P5 stages to P47–52 stages, suggesting temporal regulation of GnRH promoter activity during postnatal development in intact rats. In DEX-treated P0 males, the number of IF-GnRH neurons decreased within the medial septum, organum vasculosom of the lamina terminalis (OVLT) and anterior hypothalamus. The percentage of TG-GnRH neurons with branched dendritic structures decreased in the OVLT of DEX-P0 males. These results suggest that maternal DEX exposure affects the number and dendritic development of early postnatal GnRH neurons in the OVLT/POA, which may lead to altered reproductive functions in adults.

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Prenatal stress and glucocorticoid effects on the developing gender-related brainProceedings of Xth International Congress on Hormonal Steroids, Quebec, Canada, 17–21 June 1998.

Cited by 58 publications

References 24 publications

Early Prenatal Stress Epigenetically Programs Dysmasculinization in Second-Generation Offspring via the Paternal Lineage

Early Prenatal Stress Epigenetically Programs Dysmasculinization in Second-Generation Offspring via the Paternal Lineage

Perinatal programming of emotional brain circuits: an integrative view from systems to molecules

Maternal dexamethasone exposure during pregnancy in rats disrupts gonadotropin-releasing hormone neuronal development in the offspring

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