Prenatal stress induces long-lasting effects in lung glucocorticoid receptor gene expression in a sex-dependent manner

Autores

DOI:

https://doi.org/10.15448/1980-6108.2019.1.33192

Palavras-chave:

Prenatal stress, Lung, Glucocorticoid receptor.

Resumo

AIM: Stressful events during pregnancy may influence respiratory system development, resulting in long-term effects in the offspring. However, little is known on its long-lasting effects upon the expression of important genes in the lungs. Thus, we aimed to evaluate the effect of two different prenatal stress paradigms on lung glucocorticoid receptor (GR) expression in adulthood.
METHODS: Pregnant BALB/c mice were divided into 3 groups: control (CON), prenatal stress from the second week of pregnancy (PNS1) and prenatal stress on the last week of pregnancy (PNS2). In both groups (PNS1 and PNS2), restraint stress was used. When adults, male and female offspring were submitted to 30 min of restraint stress. Lung gene expression of GR was evaluated.
RESULTS: There was a significant increase in GR expression in males (PNS1), under basal conditions. Restraint stress during adulthood significantly reduced GR expression in PNS1 and PNS2 males as compared to controls. No significant differences were found for females.
CONCLUSION: Results indicate that prenatal stress from the second week of gestation modulates adult male mice GR expression in the lungs. Thus, fetal exposure to maternal stress from the second week of gestation seems to modulate mechanisms responsible for pulmonary development in a sex-dependent manner.

 

*** O estresse pré-natal induz efeitos de longo prazo na expressão gênica de receptores de glicocorticoides no pulmão de uma maneira dependente do sexo ***

OBJETIVO: Eventos estressores durante a gestação podem influenciar o desenvolvimento do sistema respiratório, resultando em efeitos a longo prazo na prole. No entanto, pouco se sabe sobre seus efeitos duradouros sobre a expressão de genes importantes nos pulmões. Assim, nosso objetivo foi avaliar o efeito de dois diferentes modelos de estresse pré-natal na expressão pulmonar do receptor de glicocorticoide (GR) na vida adulta.
MÉTODOS: Camundongos BALB/c prenhes foram divididas em 3 grupos: controle (CON), estresse pré-natal a partir da segunda semana de gestação (PNS1) e estresse pré-natal durante a última semana de gestação (PNS2). Nos dois grupos (PNS1 e PNS2), o estresse por contenção foi utilizado. Quando adultas, as proles machos e fêmeas foram submetidas ao estresse por contenção durante 30 min. A expressão do gene GR no pulmão foi avaliada.
RESULTADOS: Houve um aumento significativo na expressão de GR em machos (PNS1) sob condições basais. O estresse na vida adulta reduziu significativamente a expressão de GR em machos PNS1 e PNS2 em comparação aos controles. Não foram encontradas diferenças significativas em fêmeas.
CONCLUSÃO: Os resultados indicam que o estresse pré-natal a partir da segunda semana de gestação modula a expressão do GR nos pulmões de camundongos machos adultos. Assim, a exposição fetal ao estresse materno a partir da segunda semana de gestação parece modular os mecanismos responsáveis pelo desenvolvimento pulmonar de uma maneira dependente do sexo.

DESCRITORES: Estresse pré-natal; Pulmão, Receptor de glicocorticoide

 

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Biografia do Autor

Carolina Luft, Pontifícia Universidade Católica do Rio Grande do Sul

Laboratory of Pediatric Respirology, Infant Center

Natália Evangelista Campos, Pontifícia Universidade Católica do Rio Grande do Sul

Laboratory of Pediatric Respirology, Infant Center

Mauro Henrique Moraes Vargas, CNEC

Faculdade CNEC

Márcio Vinícius Fagundes Donadio, Pontifícia Universidade Católica do Rio Grande do Sul

Laboratory of Pediatric Respirology, Infant Center

Referências

McGowan PO, Matthews SG. Prenatal Stress, Glucocorticoids, and Developmental Programming of the Stress Response. Endocrinology. 2018;159(1):69-82.

https://doi.org/10.1210/en.2017-00896

Weinstock M. The long-term behavioural consequences of prenatal stress. Neuroscience and biobehavioral reviews. 2008;32(6):1073-86.

https://doi.org/10.1016/j.neubiorev.2008.03.002

Boersma GJ, Tamashiro KL. Individual differences in the effects of prenatal stress exposure in rodents. Neurobiol Stress. 2015;1:100-8.

https://doi.org/10.1016/j.ynstr.2014.10.006

Worthman CM, Kuzara J. Life history and the early origins of health differentials. American journal of human biology: the official journal of the Human Biology Council. 2005;17(1):95-112.

https://doi.org/10.1002/ajhb.20096

Bolt RJ, van Weissenbruch MM, Lafeber HN, Delemarre-van de Waal HA. Glucocorticoids and lung development in the fetus and preterm infant. Pediatr Pulmonol. 2001;32(1):76-91.

https://doi.org/10.1002/ppul.1092

Moisiadis VG, Matthews SG. Glucocorticoids and fetal programming part 1: Outcomes. Nature reviews Endocrinology. 2014;10(7):391-402.

https://doi.org/10.1038/nrendo.2014.73

Vargas MH, Campos NE, de Souza RG, da Cunha AA, Nuñez NK, Pitrez PM, Donadio MV. Protective effect of early prenatal stress on the induction of asthma in adult mice: Sex-specific differences. Physiol Behav. 2016 Oct 15;165:358-64.

https://doi.org/10.1016/j.physbeh.2016.08.023

Lee AG, Chiu YM, Rosa MJ, Cohen S, Coull BA, Wright RO, Morgan WJ, Wright RJ. Association of prenatal and early childhood stress with reduced lung function in 7-year-olds. Ann Allergy Asthma Immunol. 2017 Aug;119(2):153-9.

https://doi.org/10.1016/j.anai.2017.05.025

Barreto do Carmo MB, Righetti RF, Tibério IF, Hunziker MH. The effects of prenatal "psychological" stressor exposure on lung inflammation and hyperresponsiveness in adult rat offspring. Dev Psychobiol. 2016 Dec;58(8):1076-86.

https://doi.org/10.1002/dev.21441

Pincus-Knackstedt MK, Joachim RA, Blois SM, Douglas AJ, Orsal AS, Klapp BF, Wahn U, Hamelmann E, Arck PC. Prenatal stress enhances susceptibility of murine adult offspring toward airway inflammation. J Immunol. 2006;177(12):8484-92.

https://doi.org/10.4049/jimmunol.177.12.8484

Weinstock M. The potential influence of maternal stress hormones on development and mental health of the offspring. Brain, behavior, and immunity. 2005;19(4):296-308.

https://doi.org/10.1016/j.bbi.2004.09.006

Walker DJ, Spencer KA. Glucocorticoid programming of neuroimmune function. General and comparative endocrinology. 2018;256:80-8.

https://doi.org/10.1016/j.ygcen.2017.07.016

Harris A, Seckl J. Glucocorticoids, prenatal stress and the programming of disease. Horm Behav. 2011;59(3):279-89.

Seckl JR. Prenatal glucocorticoids and long-term programming. European journal of endocrinology. 2004;151 Suppl 3, U49-62.

https://doi.org/10.1530/eje.0.151u049

Nyirenda MJ, Lindsay RS, Kenyon CJ, Burchell A, Seckl JR. Glucocorticoid exposure in late gestation permanently programs rat hepatic phosphoenolpyruvate carboxykinase and glucocorticoid receptor expression and causes glucose intolerance in adult offspring. J Clin Invest. 1998;101(10):2174-81.

https://doi.org/10.1172/jci1567

McGowan PO, Matthews SG. Prenatal Stress, Glucocorticoids, and Developmental Programming of the Stress Response. Endocrinology. 2018; 1;159(1):69-82.

https://doi.org/10.1210/en.2017-00896

Kapoor A, Dunn E, Kostaki A, Andrews MH, Matthews SG. Fetal programming of hypothalamo-pituitaryadrenal function: prenatal stress and glucocorticoids. J Physiol. 2006;572(Pt 1):31-44.

https://doi.org/10.1113/jphysiol.2006.105254

Maeyama H, Hirasawa T, Tahara Y, Obata C, Kasai H, Moriishi K, Mochizuki K, Kubota T. Maternal restraint stress during pregnancy in mice induces 11beta-HSD1-associated metabolic changes in the livers of the offspring. J Dev Orig Health Dis. 2015 Apr;6(2):105-14.

https://doi.org/10.1017/s2040174415000100

Brunton PJ, Russell JA. Prenatal social stress in the rat programmes neuroendocrine and behavioural responses to stress in the adult offspring: sex-specific effects. J Neuroendocrinol. 2010;22(4):258-71.

https://doi.org/10.1111/j.1365-2826.2010.01969.x

Baquedano E, Garcia-Caceres C, Diz-Chaves Y, Lagunas N, Calmarza-Font I, Azcoitia I, Garcia-Segura LM, Argente J, Chowen JA, Frago LM. Prenatal stress induces long-term effects in cell turnover in the hippocampushypothalamus-pituitary axis in adult male rats. PLoS One. 2011;6(11):e27549.

https://doi.org/10.1371/journal.pone.0027549

Green MK, Rani CS, Joshi A, Soto-Piña AE, Martinez PA, Frazer A, Strong R, Morilak DA. Prenatal stress induces long term stress vulnerability, compromising stress response systems in the brain and impairing extinction of conditioned fear after adult stress. Neuroscience. 2011;192:438-51.

https://doi.org/10.1016/j.neuroscience.2011.06.041

Seale JV, Wood SA, Atkinson HC, Harbuz MS, Lightman SL. Gonadal steroid replacement reverses gonadectomyinduced changes in the corticosterone pulse profile and stress-induced hypothalamic-pituitary-adrenal axis activity of male and female rats. J Neuroendocrinol. 2004;16(12):989-98.

https://doi.org/10.1111/j.1365-2826.2004.01258.x

Iwasaki-Sekino A, Mano-Otagiri A, Ohata H, Yamauchi N, Shibasaki T. Gender differences in corticotropin and corticosterone secretion and corticotropin-releasing factor mRNA expression in the paraventricular nucleus of the hypothalamus and the central nucleus of the amygdala in response to footshock stress or psychological stress in rats. Psychoneuroendocrinology. 2009;34(2):226-37.

https://doi.org/10.1016/j.psyneuen.2008.09.003

Handa RJ, Weiser MJ. Gonadal steroid hormones and the hypothalamo-pituitary-adrenal axis. Front Neuroendocrinol. 2014;35(2):197-220.

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Publicado

2019-05-09

Como Citar

Luft, C., Campos, N. E., Vargas, M. H. M., & Donadio, M. V. F. (2019). Prenatal stress induces long-lasting effects in lung glucocorticoid receptor gene expression in a sex-dependent manner. Scientia Medica, 29(1), e33192. https://doi.org/10.15448/1980-6108.2019.1.33192

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