<i>In utero</i> glucocorticoid exposure decreases the length of small intestine at 24 hours, 1 and 3 months old.

<p>(A) The length of small intestine is shorter in <i>iuGC</i> rats at 1 and 3 months old, n = 6, 17, 6 CTR and n = 9, 10, 7 <i>iuGC</i>. (B) Stomach length in control and <i>iuGC</i> animals, n = 10, 9, 6 CTR and n = 10, 11, 7 <i>iuGC</i>. (C) The length of colon in control and <i>iuGC</i> animals, n = 10, 9, 6 CTR and n = 10, 11, 7 <i>iuGC</i>. (D) Small Intestine is shorter in <i>iuGC</i> animals at 24 hours of life, n = 4 CTR and n = 13 <i>iuGC</i>. <i>iuGC</i>, <i>in utero</i> glucocorticoid exposed animals. *<i>P</i> <0.05, *** <i>P</i> <0.001.</p

Muscularis and submucosa plus mucosa layers length in small intestine.

<p>(A) Muscularis and (B) submucosa plus mucosa layers at 1, 3 and 8 months old. There were no differences between groups. <i>iuGC</i>, <i>in utero</i> glucocorticoid exposed animals. (A) n = 6, 4, 6 CTR and n = 5, 10, 7 <i>iuGC</i>. (B) n = 6, 7, 6 CTR and n = 5, 9, 7 <i>iuGC</i>.</p

Serotonin levels, in small intestine, are decreased in <i>iuGC</i> animals at 3 months old.

<p>Serotonin levels are decreased in <i>iuGC</i> rats at 3 months old. There were no differences among groups at 1 and 8 months old, n = 10, 3, 4 CTR and n = 7, 5, 4 <i>iuGC</i>. <i>iuGC</i>, <i>in utero</i> glucocorticoid exposed animals.* <i>P</i> <0.05.</p

Prenatal treatment decreases proliferation and increases apoptosis in small intestine.

<p>(A) Proliferation was assessed by BrdU staining. (B) Proliferation rate is decreased within the crypts in <i>iuGC</i> rats, n = 3, 4, 5 CTR and n = 3, 6, 3 <i>iuGC</i>. (C) Apoptosis rate was assessed by TUNEL assay. (D) Apoptosis is increased in <i>iuGC</i> rats (mostly within the submucosa and mucosa layers), n = 6, 3, 5 CTR and n = 5, 3, 6 <i>iuGC</i>. <i>iuGC</i>, <i>in utero</i> glucocorticoid exposed animals.** <i>P</i> <0.01, *** <i>P</i> <0.001. Scale bars: 500 μm. </p

<i>iuGC</i> animals at 3 and 8 months old have a decreased GI transit.

<p><b>No differences in intestinal permeability.</b> (A) Ratio of the distance travelled by red dye and total small intestine length. Ratio is lower at 3 and 8 months old. There was no differences among groups at 1 month old (<i>P</i> = 0.07), n = 7, 17, 6 CTR and n = 6, 19, 7 <i>iuGC</i>. (B) Intestinal permeability in Control and <i>iuGC</i> animals at 1, 3 and 8 months old. There were no differences between groups, n = 3, 9, 5 CTR and n = 4, 10, 7 <i>iuGC</i>. <i>iuGC</i>, <i>in utero</i> glucocorticoid exposed animals. ** <i>P</i> <0.01, *** <i>P</i> <0.001.</p

Table_1_Mild Prenatal Stress Causes Emotional and Brain Structural Modifications in Rats of Both Sexes.DOCX

<p>Stress or high levels of glucocorticoids (GCs) during developmental periods is known to induce persistent effects in the neuroendocrine circuits that control stress response, which may underlie individuals’ increased risk for developing neuropsychiatric conditions later in life, such as anxiety or depression. We developed a rat model (Wistar han) of mild exposure to unpredictable prenatal stress (PS), which consists in a 4-h stressor administered three times per week on a random basis; stressors include strobe lights, noise and restrain. Pregnant dams subjected to this protocol present disrupted circadian corticosterone secretion and increased corticosterone secretion upon acute stress exposure. Regarding progeny, both young adult (2 months old) male and female rats present increased levels of circulating corticosterone and hyperactivity of the hypothalamus-pituitary-adrenal axis to acute stress exposure. Both sexes present anxious- and depressive-like behaviors, shown by the decreased time spent in the open arms of the elevated plus maze (EPM) and in the light side of the light-dark box (LDB), and by increased immobility time in the forced swim test, respectively. Interestingly, these results were accompanied by structural modifications of the bed nucleus of stria terminalis (BNST) and hippocampus, as well as decreased norepinephrine and dopamine levels in the BNST, and serotonin levels in the hippocampus. In summary, we characterize a new model of mild PS, and show that stressful events during pregnancy can lead to long-lasting structural and neurochemical effects in the offspring, which affect behavior in adulthood.</p

Image_1_Mild Prenatal Stress Causes Emotional and Brain Structural Modifications in Rats of Both Sexes.TIF

<p>Stress or high levels of glucocorticoids (GCs) during developmental periods is known to induce persistent effects in the neuroendocrine circuits that control stress response, which may underlie individuals’ increased risk for developing neuropsychiatric conditions later in life, such as anxiety or depression. We developed a rat model (Wistar han) of mild exposure to unpredictable prenatal stress (PS), which consists in a 4-h stressor administered three times per week on a random basis; stressors include strobe lights, noise and restrain. Pregnant dams subjected to this protocol present disrupted circadian corticosterone secretion and increased corticosterone secretion upon acute stress exposure. Regarding progeny, both young adult (2 months old) male and female rats present increased levels of circulating corticosterone and hyperactivity of the hypothalamus-pituitary-adrenal axis to acute stress exposure. Both sexes present anxious- and depressive-like behaviors, shown by the decreased time spent in the open arms of the elevated plus maze (EPM) and in the light side of the light-dark box (LDB), and by increased immobility time in the forced swim test, respectively. Interestingly, these results were accompanied by structural modifications of the bed nucleus of stria terminalis (BNST) and hippocampus, as well as decreased norepinephrine and dopamine levels in the BNST, and serotonin levels in the hippocampus. In summary, we characterize a new model of mild PS, and show that stressful events during pregnancy can lead to long-lasting structural and neurochemical effects in the offspring, which affect behavior in adulthood.</p