Sex-specific regulation of stress-induced fetal glucocorticoid surge by the mouse placenta.
Perani, Clara V
Zazara, Dimitra E
Solano, María Emilia
American journal of physiology. Endocrinology and metabolism
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Wieczorek, A., Perani, C. V., Nixon, M., Constancia, M., Sandovici, I., Zazara, D. E., Leone, G., et al. (2019). Sex-specific regulation of stress-induced fetal glucocorticoid surge by the mouse placenta.. American journal of physiology. Endocrinology and metabolism, 317 (1), E109-E120. https://doi.org/10.1152/ajpendo.00551.2018
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 mid-gestational stress in mice. We observed increased levels of maternal corticosterone, the main glucocorticoid in rodents, along with higher corticosteroid binding globulin levels at mid-gestational 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 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2; Hsd11b2 gene) and ABC transporters, which mediate glucocorticoid efflux toward maternal circulation, protect male offspring from maternal glucocorticoid surges. We generated mice with a 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 (GILZ) 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 towards the existence of sex-specific fetal glucocorticoid exposure windows during gestation in mice.
Fetus, Placenta, Animals, Mice, Inbred C57BL, Mice, Pregnancy Complications, Corticosterone, Aromatase, 11-beta-Hydroxysteroid Dehydrogenase Type 2, Receptors, Glucocorticoid, Glucocorticoids, Stress, Psychological, Pregnancy, Sex Characteristics, Female, Male
External DOI: https://doi.org/10.1152/ajpendo.00551.2018
This record's URL: https://www.repository.cam.ac.uk/handle/1810/292594
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