Prenatal betamethasone exposure has sex specific effects in reversal learning and attention in juvenile baboons

Rodriguez, Jesse S.; Zürcher, Nicole R.; Keenan, Kathryn E.; Bartlett, Thad Q.; Nathanielsz, Peter W.; Nijland, Mark J.

doi:10.1016/j.ajog.2011.01.063

Cited by 42 publications

(31 citation statements)

References 88 publications

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“…The gender-specific outcomes show a striking parallel to sex specific effects in reversal learning in juvenile baboons following late second-early third trimester administration of betamethasone, a synthetic glucocorticoid (Rodriguez et al, 2011), in which males tended to show reductions in errors while females showed enhanced error levels, effects the authors attribute to altered programming. Moreover, these sex-specific changes were also highly discrimination problem specific.…”

Section: Discussionmentioning

confidence: 82%

Enhanced stimulus sequence-dependent repeated learning in male offspring after prenatal stress alone or in conjunction with lead exposure

Cory‐Slechta¹,

Virgolini²,

Liu³

et al. 2012

NeuroToxicology

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Both lead (Pb) exposure and prenatal stress (PS) can produce cognitive deficits, and in a prior study we demonstrated enhanced cognitive deficits in repeated learning of female rats exposed to both of these developmental insults (Cory-Slechta et al., 2010). However, PS can also lead to improved cognitive outcomes that are both gender-and context-dependent. Thus, the current study examined whether Pb ± PS likewise produced repeated learning deficits in males, either after maternal or lifetime Pb exposure. Repeated learning was evaluated using a multiple schedule of repeated learning and performance that required learning 3-response sequences in male offspring that had been subjected to either maternal Pb (0 or 150 ppm) or lifetime Pb exposure (0 or 50 ppm) beginning two mos prior to dam breeding, to prenatal immobilization restraint stress (gestational days 16–17), or to both Pb and PS. Blood Pb, corticosterone, hippocampal glucocorticoid receptor density and brain monoamines were also measured. In contrast to outcomes in females, sequence-specific enhancements of repeated learning accuracy were produced by PS, particularly when combined with Pb, results that appeared to be more robust in combination with lifetime than maternal Pb exposure. A common behavioral mechanism of these improvements appears to be an increase reinforcement density associated with increased response rates and shorter session times seen with PS ± Pb that could both shorten time to reinforcement. Trends towards lower levels of nucleus accumbens dopamine activity seen after both maternal Pb and lifetime Pb combined with PS suggest a possible role for this region/neurotransmitter in enhanced accuracy, whereas PS ± Pb-induced corticosterone changes did not exhibit an obvious systematic relationship to accuracy enhancements. While PS ± Pb-based increases in accuracy appear to be an improved outcome, the benefits of increased response rate are by no means universal, but highly context-dependent and can lead to adverse behavioral effects in other conditions.

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Section: Discussionmentioning

confidence: 82%

Enhanced stimulus sequence-dependent repeated learning in male offspring after prenatal stress alone or in conjunction with lead exposure

Cory‐Slechta¹,

Virgolini²,

Liu³

et al. 2012

NeuroToxicology

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“…Animal models Male-specific outcomes Langley-Evans et al (1996) Low-protein diet gives elevated blood pressure in male offspring relative to females Rat Kwong et al (2000) Low-protein diet increases blood pressure in male offspring Rat Ozaki et al (2001) Nutrient restriction (30% reduction) increases blood pressure and vascular dysfunction more in male offspring Rat Dodic et al (2002) Dexamethasone exposure gives increased blood pressure more in male offspring Sheep Franco Mdo et al (2002) Nutrient restriction (50%) reduces eNOS expression in aorta of male offspring Rat Alexander (2003) Reduced uterine perfusion causes sustained increase in blood pressure in male offspring Rat Ortiz et al (2003) Antenatal dexamethasone injection persistently elevates blood pressure in male offspring Rat Hemmings et al (2005) Hypoxia Lee & Rivier (1996) Ethanol exposure leads to exaggerated HPA stress response in young female offspring Rat Khan et al (2003) High-fat diet increases blood pressure in female offspring Rat Wilcoxon et al (2003) Ethanol exposure leads to decreased placental 11b-hydroxysteroid dehydrogenase-2 levels and left ventricular hypertrophy in female offspring High-fat diet leads to DNA hypomethylation in female placenta only Mouse Rodriguez et al (2011) Betamethasone exposure reduces associative learning more in female offspring Baboon Vickers et al (2011) Fructose exposure gives decreased placental weight, increased plasma leptin and glucose in female offspring Rat Epidemiology Male-specific outcomes Zaren et al (2000) Maternal smoking decreases birth weight and head circumference proportionally more in male offspring Human Goldenberg et al (2006) Placentas from preterm deliveries showed more lymphohistiocytic infiltration in male offspring Human Haley et al (2006) Prenatal exposure to alcohol increases the heart rate of female infant offspring more than males, but with the males showing a greater increase in plasma cortisol Human Mingrone et al (2008) Male offspring of obese mothers have higher levels of insulin secretion in response to GTT Human Female-specific outcomes Roseboom et al (2001) Higher rates of obesity in female offspring conceived during famine Human Clifton (2005) Maternal asthma in pregnancy causes altered placental glucocorticoid metabolism and growth in female offspring Human Stark et al (2009) Antenatal betamethasone administration increased placental 11b-hydroxysteroid dehydrogenase-2 activity in female offspring and this was positively correlated with mean arterial blood pressure…”

Section: Main Results Speciesmentioning

confidence: 99%

Sex differences in developmental programming models

2013

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The theory of developmental programming suggests that diseases such as the metabolic syndrome may be 'programmed' by exposure to adverse stimuli during early development. The developmental programming literature encompasses the study of a wide range of suboptimal intrauterine environments in a variety of species and correlates these with diverse phenotypic outcomes in the offspring. At a molecular level, a large number of variables have been measured and suggested as the basis of the programmed phenotype. The range of both dependent and independent variables studied often makes the developmental programming literature complex to interpret and the drawing of definitive conclusions difficult. A common, though under-explored, theme of many developmental programming models is a sex difference in offspring outcomes. This holds true across a range of interventions, including dietary, hypoxic, and surgical models. The molecular and phenotypic outcomes of adverse in utero conditions are often more prominent in male than female offspring, although there is little consideration given to the basis for this observation in most studies. We review the evidence that maternal energy investment in male and female conceptuses may not be equal and may be environment dependent. It is suggested that male and female development could be viewed as separate processes from the time of conception, with differences in both timing and outcomes.Reproduction (2013) 145 R1-R13

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“…54,55 There is also abundant evidence of excess levels of glucocorticoids in utero impairing brain development and later behavior in humans and animal models [56][57][58][59][60][61][62][63][64][65][66][67] including baboons. 68 Although we did not assess postnatal androgen or glucocorticoid levels in offspring, this should not preclude conclusions based on gestational exposure affecting behavioral performance. Evidence does exist of elevated androgens in male rats small for gestational age.…”

Section: Discussionmentioning

confidence: 99%

Sex-Dependent Cognitive Performance in Baboon Offspring Following Maternal Caloric Restriction in Pregnancy and Lactation

et al. 2012

Self Cite

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In humans a suboptimal diet during development has negative outcomes in offspring. We investigated the behavioral outcomes in baboons born to mothers undergoing moderate maternal nutrient restriction (MNR). Maternal nutrient restriction mothers (n ¼ 7) were fed 70% of food eaten by controls (CTR, n ¼ 12) fed ad libitum throughout gestation and lactation. were administered progressive ratio, simple discrimination, intra-/extradimension set shift and delayed matching to sample tasks to assess motivation, learning, attention, and working memory, respectively. A treatment effect was observed in MNR offspring who demonstrated less motivation and impaired working memory. Nutrient-restricted female offspring showed improved learning, while MR offspring showed impaired learning and attentional set shifting and increased impulsivity. In summary, 30% restriction in maternal caloric intake has long lasting neurobehavioral outcomes in adolescent male baboon offspring.

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Prenatal betamethasone exposure has sex specific effects in reversal learning and attention in juvenile baboons

Cited by 42 publications

References 88 publications

Enhanced stimulus sequence-dependent repeated learning in male offspring after prenatal stress alone or in conjunction with lead exposure

Enhanced stimulus sequence-dependent repeated learning in male offspring after prenatal stress alone or in conjunction with lead exposure

Sex differences in developmental programming models

Sex-Dependent Cognitive Performance in Baboon Offspring Following Maternal Caloric Restriction in Pregnancy and Lactation

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