Sex-specific regulation of stress-induced fetal glucocorticoid surge by the mouse placenta.
Am J Physiol Endocrinol Metab
; 317(1): E109-E120, 2019 07 01.
Article
em En
| MEDLINE
| ID: mdl-30990748
ABSTRACT
Antenatal stress increases the prevalence of diseases in later life, which shows a strong sex-specific effect. However, the underlying mechanisms remain unknown. Maternal glucocorticoids can be elevated by stress and are potential candidates to mediate the effects of stress on the offspring sex-specifically. A comprehensive evaluation of dynamic maternal and placental mechanisms modulating fetal glucocorticoid exposure upon maternal stress was long overdue. Here, we addressed this gap in knowledge by investigating sex-specific responses to midgestational stress in mice. We observed increased levels of maternal corticosterone, the main glucocorticoid in rodents, along with higher corticosteroid-binding globulin levels at midgestation in C57Bl/6 dams exposed to sound stress. This resulted in elevated corticosterone in female fetuses, whereas male offspring were unaffected. We identified that increased placental expression of the glucocorticoid-inactivating enzyme 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2; Hsd11b2 gene) and ATP-binding cassette transporters, which mediate glucocorticoid efflux toward maternal circulation, protect male offspring from maternal glucocorticoid surges. We generated mice with an Hsd11b2 placental-specific disruption (Hsd11b2PKO) and observed moderately elevated corticosterone levels in offspring, along with increased body weight. Subsequently, we assessed downstream glucocorticoid receptors and observed a sex-specific differential modulation of placental Tsc22d3 expression, which encodes the glucocorticoid-induced leucine zipper protein in response to stress. Taken together, our observations highlight the existence of unique and well-orchestrated mechanisms that control glucocorticoid transfer, exposure, and metabolism in the mouse placenta, pinpointing toward the existence of sex-specific fetal glucocorticoid exposure windows during gestation in mice.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Placenta
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Estresse Psicológico
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Caracteres Sexuais
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Feto
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Glucocorticoides
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Pregnancy
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article