Sexual differentiation of offspring of mothers treated with cortisone during pregnancy

Treatment of pregnant rats with hydrocortisone (1.5 or 3.0 mg) from Day 14 after conception until birth resulted in shortened anogenital distance and lowered testis weight in male offspring. No changes were found in female anogenital distance. It was concluded that corticosteroids, like stress, during pregnancy causes demasculinization of the male offspring     

Comparative effects of a prenatal stress occurring during early or late gestation on pig immune response

The aim of this work was to investigate the immune effects of prenatal stress (PNS) in pigs, when maternal stressor is applied during early or late gestation. In two separate experiments, gilts were submitted to a social-stress routine between either days 24 and 48 (stress (S) group, n = 8 vs. control (C) group, n = 6) or days 79 and 103 of gestation (S group, n = 10 vs. C group, n = 7). During the first month of life of the piglets, their cortisol levels were assessed in basal state and after stressful events (castration, new environment, and weaning). Piglets were immunized against ovalbumin (OVA) at 7 (D7) and 19 (D19) days of age. Lymphocyte proliferation in response to OVA and mitogens was investigated in blood in both sexes from D5 to D29 as well as in the spleen, thymus and crural lymph nodes from females euthanized on D5 and D26. On D27, the cytokine response of male piglets to an injection of lipopolysaccharide was investigated. Special care was taken to minimize the stress at blood sampling and euthanasia. We found that early gestational stress only affected the relative weight of adrenals on D5 (S < C, P < 0.05). On the contrary, late gestational stress increased the proliferation index of blood cells regardless of the age, in both sexes in response to PHA (P = 0.06), and in females only in response to ConA (P < 0.01) and PWM (P < 0.05). Overall, the effects of PNS in pigs seem to depend on the stage of gestation, gender and the immune compartment.     

Maternal use of flaxseed oil during pregnancy and lactation prevents morphological alterations in pancreas of female offspring from rat dams with experimental diabetes

Nutritional recommendations have promoted the increased need to consume n‐3 polyunsaturated fatty acids. Flaxseed is the richest dietary source of n‐3 fatty acids among plant sources and is widely used for its edible oil. This study aimed to investigate whether maternal use of flaxseed oil has effects on pancreas morphology in the female offspring of diabetic mothers. Female Wistar rats (n = 12) were induced into diabetes by a high‐fat diet and low dose of streptozotocin. After confirmation of the diabetes, rats were mated, and once pregnancy was confirmed, they were allocated into three groups (n = 6): high‐fat group (HG); flaxseed oil group (FOG); and control group (CG) (non‐diabetic rats). At weaning, female offspring (n = 6/group) received standard chow diet. The animals were euthanized at 180 days. Pancreas was collected for histomorphometric and immunohistochemistry analysis. HG showed hypertrophy of pancreatic islets (P < 0.0001), whereas FOG offspring had islets with smaller diameters compared to HG (P < 0.0001). HG offspring showed higher percentage of larger (P = 0.0061) and lower percentage of smaller islets (P = 0.0036). HG showed lower islet insulin immunodensity at 180 days (P < 0.0001), whereas FOG was similar to CG (P < 0.0001). Flaxseed oil reduced the damage caused by maternal hyperglycaemia, promoting normal pancreas histomorphometry and β‐cell mass in female offspring.     

孕期非那雄胺暴露致子代雄性小鼠生殖器官发育异常

目的:探讨孕期非那雄胺暴露对子代雄性小鼠生殖器官发育的影响。方法:CD-1小鼠在受孕后0～17 d给予非那雄胺处理,通过宏观观察、解剖分析与组织形态学染色观察子代雄性小鼠生殖器官的发育情况;通过免疫荧光染色分析子代雄性小鼠精子发生情况。结果:宏观观察结果显示,孕期非那雄胺暴露可导致子代雄性小鼠外生殖器官畸形,表现为阴囊未完全融合及阴茎畸形;此外,还观察到小鼠肛门与生殖器的距离显著缩短(P<0.01)。解剖分析结果显示,孕期非那雄胺暴露可导致子代雄性小鼠睾丸不同程度的不完全下降及长度显著缩短(P<0.01)。组织形态学结果显示,各阶段阴茎长度均显著缩短(P<0.01);睾丸生精小管密度和生精小管管腔成熟精子数均显著降低(P<0.01),生精小管管腔和睾丸间质间隙均显著增大(P<0.01)。免疫荧光染色结果显示,睾丸中支持细胞、睾丸间质细胞和精原细胞的密度均显著降低(P<0.01);生精小管细胞的caspase-3荧光强度显著增加(P<0.01),Ki67与沙漠刺猬因子(desert hedgehog,Dhh)荧光强度均显著降低(P<0.01...     

Effect of maternal weight during pregnancy on offspring muscle strength response to resistance training in late adulthood

Purpose

Maternal obesity can unfavorably influence offspring body composition, muscle strength, and possibly muscle’s adaptability to training, but the human studies are scarce. Therefore, we aimed to investigate the effect of maternal obesity on offspring muscle strength responses to resistance training intervention in elderly frail women.

Sleep restriction during pregnancy: hypertension and renal abnormalities in young offspring rats

Study Objectives:

Because the maternal environment can affect several physiological functions of the newborn, the aim of the present study was to examine the impact of sleep restriction during pregnancy on renal morphology and function in young offspring.

Design:

Female 3-month-old Wistar rats were divided in 2 experimental groups: C (control) and SR (sleep restriction between the 14th and 20th day of pregnancy). Pregnancy was confirmed by vaginal smear. SR females were subjected to sleep restriction by the multiple platform technique for 20 h daily. After birth, only male litters (6 for each mother) were selected and designated OC (offspring from C) and OSR (offspring from SR). At 2 months of age, blood pressure (BP) was measured by tail plethysmography; at 3 months the renal plasma flow (RPF), glomerular filtration rate (GFR), glomerular area, and number of glomeruli per mm³ were evaluated.

Measurements and Results:

Offspring from SR had higher systolic blood pressure than OC. In this group (OSR), we also observed significant increase in RPF and GFR, enlarged glomeruli diameter, and reduced number of glomeruli per mm³ of renal tissue.

Conclusions:

Our data suggest that sleep restriction during pregnancy is able to modify renal development, resulting in morphologic and functional alterations in young offspring.

Citation:

Thomal JT; Palma BD; Ponzio BF; Franco MCP; Zaladek-Gil F; Fortes ZB; Tufik S; Gomes GN. Sleep restriction during pregnancy: hypertension and renal abnormalities in young offspring rats. SLEEP 2010;33(10):1357-1362.     

Acute blockade of endogenous melatonin by Luzindole,with or without peripheral LPS injection,induces jejunal inflammation and morphological alterations in Swiss mice

This study investigated the acute blockade of endogenous melatonin (MLT) using Luzindole with or without systemic lipopolysaccharide (LPS) challenge and evaluated changes in inflammatory and oxidative stress markers in the mouse jejunum. Luzindole is an MT1/MT2 MLT receptor antagonist. Both receptors occur in the small intestine. Swiss mice were treated with either saline (0.35 mg/kg, ip), Luzindole (0.35 mg/kg, ip), LPS (1.25 mg/kg, ip), or Luzindole+LPS (0.35 and 1.25 mg/kg, ip, respectively). Jejunum samples were evaluated regarding intestinal morphometry, histopathological crypt scoring, and PAS-positive villus goblet cell counting. Inflammatory Iba-1, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, nuclear factor (NF)-kB, myeloperoxidase (MPO), and oxidative stress (NP-SHs, catalase, MDA, nitrate/nitrite) markers were assessed. Mice treated with Luzindole, LPS, and Luzindole+LPS showed villus height shortening. Crypt damage was worse in the LPS group. Luzindole, LPS, and Luzindole+LPS reduced the PAS-goblet cell labeling and increased Iba-1-immunolabelled cells compared to the saline group. Immunoblotting for IL-1β, TNF-α, and NF-kB was greater in the Luzindole group. The LPS-challenged group showed higher MPO activity than the saline and Luzindole groups. Catalase was reduced in the Luzindole and Luzindole+LPS groups compared to saline. The Luzindole group showed an increase in NP-SHs, an effect related to compensatory GSH activity. The acute blockade of endogenous MLT with Luzindole induced early changes in inflammatory markers with altered intestinal morphology. The other non-detectable deleterious effects of Luzindole may be balanced by the unopposed direct action of MLT in immune cells bypassing the MT1/MT2 receptors.     

Use of hair cortisol analysis to detect hypercortisolism during active drinking phases in alcohol-dependent individuals

The assessment of cortisol levels in human hair has recently been suggested to provide a retrospective index of cumulative cortisol exposure over periods of up to 6 months. The current study examined the utility of hair cortisol analysis to retrospectively detect hypercortisolism during active drinking phases in alcoholics in acute withdrawal (n = 23), the normalisation of cortisol output in abstinent alcoholics (n = 25) and cortisol levels in age- and gender-matched controls (n = 20). Scalp-near 3-cm hair segments were sampled and analysed for cortisol content. Results showed three to fourfold higher cortisol levels in hair samples of alcoholics in acute withdrawal than in those of abstinent alcoholics (p < .001) or controls (p < .001), with no differences between the latter two groups. The current hair cortisol findings closely mirror results of previous research using well-established measures of systemic cortisol secretion and thus provide further validation of this novel method.     

肾上腺素对小鼠巨噬细胞中促炎／抗炎介质比值的影响

目的：研究肾上腺素对脂多糖（LPS）诱导的小鼠单核巨噬细胞株RAW264.7中促炎介质［肿瘤坏死因子（TNF-α）、一氧化氮（NO）、环加氧酶-2（COX-2）］和抗炎介质［血红素氧化酶-1（HO-1）、白介素10（IL-10）］表达及NF-κB活化的影响。 方法： 以10 μg/L的LPS刺激体外培养的RAW264.7细胞作为炎症模型，加入不同浓度的肾上腺素（1、5、10、50 μmol/L）孵育24 h后，收集培养上清并提取细胞总蛋白，酶联免疫法测定上清中TNF-α、IL-10浓度，Griess法检测上清NO含量(以NO2-/NO3-表示)，免疫印迹法检测细胞总蛋白中COX-2、HO-1、IκB-α的含量。 结果： 10 μg/L的LPS明显诱导TNF-α、NO(NO2-/NO3-)、COX-2、IL-10及HO-1的产生；LPS+肾上腺素组与LPS单独作用组相比促炎介质TNF-α、NO(NO2-/NO3-)、COX-2的表达量显著下降，而抗炎介质IL-10、HO-1的表达却明显增强；肾上腺素与LPS共同作用组中IκB-α的含量与单独LPS作用组相比无明显差异。 结论： 肾上腺素下调LPS诱导的巨噬细胞中促炎介质的表达同时促进抗炎介质的表达，这种效应并不通过影响NF-κB的活化来实现。     

Dysregulated diurnal cortisol pattern is associated with glucocorticoid resistance in women with major depressive disorder

Dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis is believed to play a role in the pathophysiology of depression. To investigate mechanisms that may underlie this effect, we examined several indices of HPA axis function – specifically, diurnal cortisol slope, cortisol awakening response, and suppression of cortisol release following dexamethasone administration – in 26 pre-menopausal depressed women and 23 never depressed women who were matched for age and body mass index. Salivary cortisol samples were collected at waking, 30 min after waking, and at bedtime over three consecutive days. On the third day, immediately after the bedtime sample, participants ingested a 0.5 mg dexamethasone tablet; they then collected cortisol samples at waking and 30 min after waking the following morning. As predicted, depressed women exhibited flatter diurnal cortisol rhythms and more impaired suppression of cortisol following dexamethasone administration than non-depressed women over the three sampling days. In addition, flatter diurnal cortisol slopes were associated with reduced cortisol response to dexamethasone treatment, both for all women and for depressed women when considered separately. Finally, greater self-reported depression severity was associated with flatter diurnal cortisol slopes and with less dexamethasone-related cortisol suppression for depressed women. Depression in women thus appears to be characterized by altered HPA axis functioning, as indexed by flatter diurnal cortisol slopes and an associated impaired sensitivity of cortisol to dexamethasone. Given that altered HPA axis functioning has been implicated in several somatic conditions, the present findings may be relevant for understanding the pathophysiology of both depression and depression-related physical disease.     

Consequences of maternal psychological stress during pregnancy for the risk of asthma in the offspring

Asthma is a common lung condition that makes breathing difficult through the inflammation and constriction of the lung airways. Epidemiological evidence supports the presence of a positive association between prenatal maternal psychological stress (PMPS) and asthma in the offspring, suggesting the disease may have developmental origins. T‐helper 2 (Th2) cells are a major subtype of T‐helper cells, producing Th2 cytokines, which may be the main drivers of asthma symptoms. A Th2 dominant blood cytokine profile may therefore indicate an increased risk of asthma, as studies have shown a link between PMPS and a T‐helper 2 (Th2) cytokine profile in offspring. The mechanism by which PMPS may cause Th2 cytokine dominance in the offspring is unclear. Epigenetic modifications in utero can lead to long‐lasting effects that persist postnatally and have therefore been implicated in this relationship. Increased maternal blood cortisol levels due to PMPS may increase transfer of cortisol to the foetus, where the temporarily increased levels may induce changes in the epigenome. Evidence from animal studies suggests that genes controlling cytokine production in T cells can be epigenetically modified in a way that increases Th2 cytokine production. Other evidence suggests that methylation of the NR3C1 gene decreases hippocampal glucocorticoid receptor expression, leading to decreased negative regulation of the hypothalamus‐pituitary‐adrenal axis. This can increase cortisol production which has been shown to increase Th2 cytokine production. Therefore, the link between PMPS and a Th2 offspring cytokine profile, mediated through epigenetic changes, may explain the positive relationship between PMPS and asthma in the offspring.     

Chronic schistosomiasis during pregnancy epigenetically reprograms T‐cell differentiation in offspring of infected mothers

Schistosomiasis is a nontransplacental helminth infection. Chronic infection during pregnancy suppresses allergic airway responses in offspring. We addressed the question whether in utero exposure to chronic schistosome infection (Reg phase) in mice affects B‐cell and T‐cell development. Therefore, we focused our analyses on T‐cell differentiation capacity induced by epigenetic changes in promoter regions of signature cytokines in offspring. Here, we show that naïve T cells from offspring of schistosome infected female mice had a strong capacity to differentiate into T_H1 cells, whereas T_H2 differentiation was impaired. In accordance, reduced levels of histone acetylation of the IL‐4 promoter regions were observed in naïve T cells. To conclude, our mouse model revealed distinct epigenetic changes within the naïve T‐cell compartment affecting T_H2 and T_H1 cell differentiation in offspring of mothers with chronic helminth infection. These findings could eventually help understand how helminths alter T‐cell driven immune responses induced by allergens, bacterial or viral infections, as well as vaccines.     

Neuropeptide S receptor gene is associated with cortisol responses to social stress in humans

The neuropeptide S (NPS) and its receptor NPSR represent a transmitter system critically involved in the modulation of anxiety and arousal in rodents. Initial human studies indicate that the T-allele of the functional NPSR gene (NPSR1) polymorphism (rs324981), which increases NPS potency at NPSR, is associated with anxiety-related phenotypes. Since stress is critically involved in the pathogenesis of anxiety disorders, we tested the association between rs324981 and stress reactivity in 196 healthy males. Participants were exposed to the Trier Social Stress Test for Groups (TSST-G), a standardized laboratory protocol for stress exposure in a group format. Salivary cortisol and subjective stress responses were assessed. A significant genotype by time interaction and a main effect of genotype were shown, with T-allele carriers displaying larger cortisol and subjective stress responses. This is the first report to show involvement of the NPS system in the regulation of the neuroendocrine stress response in humans.     

Neonatal outcomes in offspring of women with anxiety and depression during pregnancy

Summary Background: The presence of mental disorder during pregnancy could affect the offspring.Aims: To examine the effects of anxiety disorder and depression in pregnant women on neonatal outcomes, and to compare neonatal outcomes between offspring of attendees and non-attendees in a general population-based health survey.Method: Pregnant women (n = 680) were identified from the population-based health study of Nord-TrØndelag County (HUNT-2) by linkage with the Medical Birth Registry of Norway. The women rated themselves on the Hospital Anxiety and Depression Rating Scale (HADS). Outcome variables were gestational length, birth weight, and Apgar scores.Results: HADS-defined anxiety disorder during pregnancy was associated with lower Apgar score at one minute (score < 8; odds ratio = 2.27; p = .03) and five minutes (score < 8; odds ratio = 4.49; p = .016). No confounders were identified. Anxiety disorder and depression during pregnancy was not associated with low birth weight or preterm delivery. Offspring of non-attendees had a lower birth weight (77 g; t = 3.27; p = 0.001) and a shorter gestational length (1.8 days; t = 2.76; p = 0.006) than that of offspring of attendees, a difference that may be explained by a higher load of psychosocial risk factors among the non-attendees.Conclusion: In our study that may be biased towards the healthier among pregnant women, anxiety disorder or depression during pregnancy were not strong risk factors for adverse neonatal outcomes although low Apgar score in offspring of women with anxiety disorder may indicate poor neonatal adaptation.     

Maternal tolerance achieved during pregnancy is transferred to the offspring via breast milk and persistently protects the offspring from allergic asthma

Background Maternal, more than paternal, asthma is a risk factor for the development of asthma in children. Recently, epidemiologic studies have shown that environmental exposures during pregnancy might influence the development of childhood asthma and allergies. Objective The aim of the present study was to investigate whether the induction of tolerance against a specific antigen during pregnancy prevents in the offspring the development of allergic asthma in response to this antigen. Methods Balb/c mice were orally tolerized with ovalbumin (OVA) during pregnancy. The offspring of tolerized and naïve mothers were immunized with OVA at 6 weeks and 4 months of age and analysed in our murine asthma model. Results While the offspring of naïve mice developed increased AHR, eosinophilic airway inflammation, T‐helper type 2 cytokine production and high serum IgE levels in response to OVA sensitization, the offspring of tolerized mice were almost completely protected from asthma, even when immunized as late as 4 months after birth. Breastfeeding was crucial for protection because tolerance was only observed when the offspring were nursed by their own mothers and not when nursed by naïve wet‐nurses. Allergen‐specific IgG₁ antibodies were exclusively increased in the breast milk of tolerant mothers and serum of protected pups, indirectly supporting its important role in tolerance transfer from the mother to the offspring. Sensitization of the F1 generation from OVA‐tolerized mothers with a heterologous allergen enhanced the immune response to this antigen. Conclusion Our results demonstrate that mucosal allergen contact during pregnancy modifies the asthma and allergy risk of the offspring mediated via breast milk. This observation may suggest that the time window for primary prevention strategies starts even before early childhood during pregnancy.     

Intercollegiate soccer: saliva cortisol and testosterone are elevated during competition, and testosterone is related to status and social connectedness with team mates

Men and women from a southern university's intercollegiate varsity soccer teams gave saliva samples before and after league matches. For the men, samples were collected for a single game ending in victory. For the women, samples were collected for two games, one of which ended in victory and the other in defeat. For both men and women, match competition substantially increased saliva cortisol (C) and testosterone (T). For women, play-related increases in saliva C and T were similar in victory and defeat. For both men and women, saliva T (but not C) was highly correlated with teammate ratings of playing abilities--one measure of status with teammates--and self-ratings of social connectedness with teammates, but the nature of the relationship was different according to sex. For men, play-related changes in T were positively correlated with these variables, but before-game T was not. For women, before-game T was positively related to each of these variables, but play-related changes in T were not. Status and social connectedness are pertinent to understanding interpersonal dynamics in most social groups, and these results--which link T and these variables in an athletic context--may have relevance for understanding social relationships in other settings.