Early Dexamethasone Treatment Induces Placental Apoptosis in Sheep

T Braun, W Meng, H Shang, Shaofu Li, DM Sloboda, W Ehrlich, K Lange, H Xu, W Henrich, JW Dudenhausen, A Plagemann, John Newnham, John Challis

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    Abstract

    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 = 105) were randomized to control (n = 56, 2 mL saline/ewe) or DEX treatment (n = 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.
    Original languageEnglish
    Pages (from-to)47-59
    JournalReproductive Sciences
    Volume22
    Issue number1
    DOIs
    Publication statusPublished - Jan 2015

    Fingerprint

    Dexamethasone
    Sheep
    Apoptosis
    Pregnancy
    Cell Count
    Placentation
    Therapeutics
    Fetal Development
    Pregnancy Proteins
    Placental Lactogen
    Intramuscular Injections
    Proliferating Cell Nuclear Antigen
    Placenta
    Glucocorticoids
    Fetus
    Weights and Measures

    Cite this

    Braun, T., Meng, W., Shang, H., Li, S., Sloboda, DM., Ehrlich, W., ... Challis, J. (2015). Early Dexamethasone Treatment Induces Placental Apoptosis in Sheep. Reproductive Sciences, 22(1), 47-59. https://doi.org/10.1177/1933719114542028
    Braun, T ; Meng, W ; Shang, H ; Li, Shaofu ; Sloboda, DM ; Ehrlich, W ; Lange, K ; Xu, H ; Henrich, W ; Dudenhausen, JW ; Plagemann, A ; Newnham, John ; Challis, John. / Early Dexamethasone Treatment Induces Placental Apoptosis in Sheep. In: Reproductive Sciences. 2015 ; Vol. 22, No. 1. pp. 47-59.
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    abstract = "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 = 105) were randomized to control (n = 56, 2 mL saline/ewe) or DEX treatment (n = 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.",
    author = "T Braun and W Meng and H Shang and Shaofu Li and DM Sloboda and W Ehrlich and K Lange and H Xu and W Henrich and JW Dudenhausen and A Plagemann and John Newnham and John Challis",
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    Braun, T, Meng, W, Shang, H, Li, S, Sloboda, DM, Ehrlich, W, Lange, K, Xu, H, Henrich, W, Dudenhausen, JW, Plagemann, A, Newnham, J & Challis, J 2015, 'Early Dexamethasone Treatment Induces Placental Apoptosis in Sheep' Reproductive Sciences, vol. 22, no. 1, pp. 47-59. https://doi.org/10.1177/1933719114542028

    Early Dexamethasone Treatment Induces Placental Apoptosis in Sheep. / Braun, T; Meng, W; Shang, H; Li, Shaofu; Sloboda, DM; Ehrlich, W; Lange, K; Xu, H; Henrich, W; Dudenhausen, JW; Plagemann, A; Newnham, John; Challis, John.

    In: Reproductive Sciences, Vol. 22, No. 1, 01.2015, p. 47-59.

    Research output: Contribution to journalArticle

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    AU - Ehrlich, W

    AU - Lange, K

    AU - Xu, H

    AU - Henrich, W

    AU - Dudenhausen, JW

    AU - Plagemann, A

    AU - Newnham, John

    AU - Challis, John

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    N2 - 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 = 105) were randomized to control (n = 56, 2 mL saline/ewe) or DEX treatment (n = 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.

    AB - 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 = 105) were randomized to control (n = 56, 2 mL saline/ewe) or DEX treatment (n = 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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