Sex-Specific Effects of Prenatal Glucocorticoids on Placental Development

Dickinson, Hayley; O'Connell, Bree Aimee; Walker, David W.; Moritz, Karen M.

doi:10.5772/50200

Cited by 9 publications

(10 citation statements)

References 113 publications

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“…19,21,55,82 Differences in the distribution of placentome subtypes and/or function may contribute to these sexspecific responses to antenatal GC, and we now show that increased placental apoptosis in females may be a contributing factor. This contributing role of the placenta has also been observed in GC metabolizing enzymes which protect the fetus from high levels of endogenous cortisol 83 where in normal term pregnancies, females have higher levels of placental 11bHSD-2 activity compared to males. 84 These differences in enzyme activity may suggest that the female fetus could be exposed to lower maternally derived cortisol and thus escapes negative-feedback regulation, facilitating autonomous development of fetal HPA function.…”

Section: Braun Et Al 55mentioning

confidence: 90%

Early Dexamethasone Treatment Induces Placental Apoptosis in Sheep

et al. 2015

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Glucocorticoid treatment given in late pregnancy in sheep resulted in altered placental development and function. An imbalance of placental survival and apoptotic factors resulting in an increased rate of apoptosis may be involved. We have now investigated the effects of dexamethasone (DEX) in early pregnancy on binucleate cells (BNCs), placental apoptosis, and fetal sex as a determinant of these responses. Pregnant ewes carrying singleton fetuses (n ¼ 105) were randomized to control (n ¼ 56, 2 mL saline/ewe) or DEX treatment (n ¼ 49, intramuscular injections of 0.14 mg/kg ewe weight per 12 hours over 48 hours) at 40 to 41 days of gestation (dG). Placentomes were collected at 50, 100, 125, and 140 dG. At 100 dG, DEX in females reduced BNC numbers, placental antiapoptotic (proliferating cell nuclear antigen), and increased proapoptotic factors (Bax, p53), associated with a temporarily decrease in fetal growth. At 125 dG, BNC numbers and apoptotic markers were restored to normal. In males, ovine placental lactogen-protein levels after DEX were increased at 50 dG, but at 100 and 140 dG significantly decreased compared to controls. In contrast to females, these changes were independent of altered BNC numbers or apoptotic markers. Early DEX was associated with sex-specific, transient alterations in BNC numbers, which may contribute to changes in placental and fetal development. Furthermore, in females, altered placental apoptosis markers may be involved.

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Section: Braun Et Al 55mentioning

confidence: 90%

Early Dexamethasone Treatment Induces Placental Apoptosis in Sheep

et al. 2015

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“…The onset of labor involves biochemical interactions among mother, fetus, and placenta. An emerging body of evidence suggests that human placentas are sexually dimorphic in their response to excess maternal glucocorticoids (Davis and Pfaff, ; Dickinson et al, ). While our test does not contribute to the debate over which biochemical interactions link the external environment to the scheduling of parturition, we assume, consistent with the dysregulated parturition narrative, that components of the maternal stress response play an important role.…”

Section: Discussionmentioning

confidence: 99%

Timing of birth: Parsimony favors strategic over dysregulated parturition

Catalano

Goodman

Margerison-Zilko

et al. 2015

American J Hum Biol

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“…Maternal exposure to glucocorticoids has been shown in a number of species to alter placental development and programme sex specific disease outcomes in offspring (Dickinson et al . ; Singh et al . ).…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have demonstrated that increased glucocorticoid concentrations during pregnancy can alter placental function and lead to sex specific disease outcomes in offspring with male offspring often more overtly impaired than female offspring (Dickinson et al . ). We have previously demonstrated that short‐term administration of the endogenous glucocorticoid, corticosterone, to pregnant mice has no impact on fetal weight but increases placental weight and alters the composition of the placenta in male, but not female fetuses (Cuffe et al .…”

Section: Introductionmentioning

confidence: 97%

Maternal corticosterone in the mouse alters oxidative stress markers, antioxidant function and mitochondrial content in placentas of female fetuses

Bartho

Holland

Moritz

et al. 2019

The Journal of Physiology

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Key points Maternal exposure to the stress hormone corticosterone is known to programme a range of sex specific disease outcomes in offspring. Sex differences in placental adaptations are thought to mediate these processes. Placental oxidative stress is implicated in a range of pregnancy disorders but the role of placental oxidative stress in sex specific disease outcomes following prenatal corticosterone exposure is unknown. This study demonstrates that maternal corticosterone reduced placental hydrogen peroxide and 8‐hydroxy‐2′‐deoxyguanosine concentrations but increased protein carbonyl content and advanced glycation end product concentrations in placentas of female fetuses but not male fetuses. These results highlight that placentas of female fetuses respond differently to maternal corticosterone exposure, with oxidative stress a major finding in placentas of female fetuses. Abstract Maternal exposure to glucocorticoids during pregnancy increases offspring risk of developing a range of sex specific disease phenotypes. These sex specific disease outcomes are thought to be in part mediated by different placental adaptations in males and females. The placenta is a highly metabolic organ which is vulnerable to the effects of oxidative stress. In other tissues, males and females have been shown to respond differently to the pro‐oxidant effects of glucocorticoids. This study therefore used a well characterized animal model of maternal corticosterone exposure to investigate sex specific alterations in reactive oxygen species production, antioxidant concentrations and mitochondrial properties that might contribute to sex differences in placental outcomes. C57BL/6 mice were implanted with osmotic minipumps containing corticosterone (33 μg kg−1 h−1) at embryonic day (E) 12.5 and placentas collected at E14.5 for analysis. Corticosterone exposure reduced placental hydrogen peroxide (H2O2) and 8‐hydroxy‐2′‐deoxyguanosine concentrations but increased protein carbonyl content and advanced glycation end product concentrations in placentas of female fetuses but not male fetuses. This dysregulation of different markers of oxidative stress may be due to increased placental activity of thioredoxin reductase in female but not male fetuses. Corticosterone reduced placental mitochondrial content but increased protein expression of the autophagosome cargo protein p62. This study demonstrates that placentas of female fetuses respond differently to maternal corticosterone exposure and highlights an important role of reactive oxygen species, mitochondrial adaptations and antioxidant responses in glucocorticoid induced programmed disease.

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Sex-Specific Effects of Prenatal Glucocorticoids on Placental Development

Cited by 9 publications

References 113 publications

Early Dexamethasone Treatment Induces Placental Apoptosis in Sheep

Early Dexamethasone Treatment Induces Placental Apoptosis in Sheep

Timing of birth: Parsimony favors strategic over dysregulated parturition

Maternal corticosterone in the mouse alters oxidative stress markers, antioxidant function and mitochondrial content in placentas of female fetuses

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