Do Alterations in Placental 11β-Hydroxysteroid Dehydrogenase (11βHSD) Activities Explain Differences in Fetal Hypothalamic-Pituitary-Adrenal (HPA) Function Following Periconceptional Undernutrition or Twinning in Sheep?

K.L. Connor, John Challis, P. Van Zijl, C.W. Rumball, S. Alix, A.L. Jaquiery, M.H. Oliver, J.E. Harding, F.H. Bloomfield

    Research output: Contribution to journalArticle

    19 Citations (Scopus)

    Abstract

    Periconceptional undernutrition (UN) in sheep accelerates fetal hypothalamic-pituitary-adrenal (HPA) axis activation, resulting in preterm birth. In contrast, twin conception suppresses fetal HPA function and delays prepartum HPA activation. We hypothesized that these dissimilar effects on fetal HPA activity result from different influences of maternal glucocorticoid (GC) on maturation of the fetal HPA axis, mediated via different activities of placental 11β-hydroxysteroid dehydrogenase (11βHSD) isozymes. We examined the effects of twinning and maternal periconceptional UN from 60 days before until 30 days after mating on the ontogeny of placental 11βHSD-1 and -2 enzyme activities. At day 85 of gestation, placental 11βHSD-2 activity was lower in UN than in normally nourished (N) fetuses (P <.05) and was higher in twins than in singletons (P <.05). Furthermore, placental 11βHSD-1 activity was not different between nutritional groups but was higher in twins than in singletons (P = .01). At day 85, fetal plasma cortisol (P <.001) and cortisone (P <.001) concentrations were lower in UN than in N fetuses, but the cortisol to cortisone ratio was higher in UN than in N fetuses (P = .01). There was no effect of fetus number on plasma cortisol or cortisone concentrations or on the ratio of cortisol to cortisone at day 85. Therefore, periconceptional UN and twinning may result in the alterations of placental 11βHSD isozyme activities at particular times during gestation. Changes in these activities during critical periods of fetal development could affect transplacental transfer or placental generation of GCs that reach the fetus, potentially influencing the timing of activation of the fetal HPA axis, fetal maturation, and hence the development and health later in life.
    Original languageEnglish
    Pages (from-to)1201-1212
    JournalReproductive Sciences
    Volume16
    Issue number12
    DOIs
    Publication statusPublished - 2009

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    11-beta-Hydroxysteroid Dehydrogenases
    Malnutrition
    Sheep
    Cortisone
    Fetus
    Hydrocortisone
    Isoenzymes
    Mothers
    Pregnancy
    Premature Birth
    Fetal Development
    Glucocorticoids
    Health
    Enzymes

    Cite this

    Connor, K.L. ; Challis, John ; Van Zijl, P. ; Rumball, C.W. ; Alix, S. ; Jaquiery, A.L. ; Oliver, M.H. ; Harding, J.E. ; Bloomfield, F.H. / Do Alterations in Placental 11β-Hydroxysteroid Dehydrogenase (11βHSD) Activities Explain Differences in Fetal Hypothalamic-Pituitary-Adrenal (HPA) Function Following Periconceptional Undernutrition or Twinning in Sheep?. In: Reproductive Sciences. 2009 ; Vol. 16, No. 12. pp. 1201-1212.
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    title = "Do Alterations in Placental 11β-Hydroxysteroid Dehydrogenase (11βHSD) Activities Explain Differences in Fetal Hypothalamic-Pituitary-Adrenal (HPA) Function Following Periconceptional Undernutrition or Twinning in Sheep?",
    abstract = "Periconceptional undernutrition (UN) in sheep accelerates fetal hypothalamic-pituitary-adrenal (HPA) axis activation, resulting in preterm birth. In contrast, twin conception suppresses fetal HPA function and delays prepartum HPA activation. We hypothesized that these dissimilar effects on fetal HPA activity result from different influences of maternal glucocorticoid (GC) on maturation of the fetal HPA axis, mediated via different activities of placental 11β-hydroxysteroid dehydrogenase (11βHSD) isozymes. We examined the effects of twinning and maternal periconceptional UN from 60 days before until 30 days after mating on the ontogeny of placental 11βHSD-1 and -2 enzyme activities. At day 85 of gestation, placental 11βHSD-2 activity was lower in UN than in normally nourished (N) fetuses (P <.05) and was higher in twins than in singletons (P <.05). Furthermore, placental 11βHSD-1 activity was not different between nutritional groups but was higher in twins than in singletons (P = .01). At day 85, fetal plasma cortisol (P <.001) and cortisone (P <.001) concentrations were lower in UN than in N fetuses, but the cortisol to cortisone ratio was higher in UN than in N fetuses (P = .01). There was no effect of fetus number on plasma cortisol or cortisone concentrations or on the ratio of cortisol to cortisone at day 85. Therefore, periconceptional UN and twinning may result in the alterations of placental 11βHSD isozyme activities at particular times during gestation. Changes in these activities during critical periods of fetal development could affect transplacental transfer or placental generation of GCs that reach the fetus, potentially influencing the timing of activation of the fetal HPA axis, fetal maturation, and hence the development and health later in life.",
    author = "K.L. Connor and John Challis and {Van Zijl}, P. and C.W. Rumball and S. Alix and A.L. Jaquiery and M.H. Oliver and J.E. Harding and F.H. Bloomfield",
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    Do Alterations in Placental 11β-Hydroxysteroid Dehydrogenase (11βHSD) Activities Explain Differences in Fetal Hypothalamic-Pituitary-Adrenal (HPA) Function Following Periconceptional Undernutrition or Twinning in Sheep? / Connor, K.L.; Challis, John; Van Zijl, P.; Rumball, C.W.; Alix, S.; Jaquiery, A.L.; Oliver, M.H.; Harding, J.E.; Bloomfield, F.H.

    In: Reproductive Sciences, Vol. 16, No. 12, 2009, p. 1201-1212.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Do Alterations in Placental 11β-Hydroxysteroid Dehydrogenase (11βHSD) Activities Explain Differences in Fetal Hypothalamic-Pituitary-Adrenal (HPA) Function Following Periconceptional Undernutrition or Twinning in Sheep?

    AU - Connor, K.L.

    AU - Challis, John

    AU - Van Zijl, P.

    AU - Rumball, C.W.

    AU - Alix, S.

    AU - Jaquiery, A.L.

    AU - Oliver, M.H.

    AU - Harding, J.E.

    AU - Bloomfield, F.H.

    PY - 2009

    Y1 - 2009

    N2 - Periconceptional undernutrition (UN) in sheep accelerates fetal hypothalamic-pituitary-adrenal (HPA) axis activation, resulting in preterm birth. In contrast, twin conception suppresses fetal HPA function and delays prepartum HPA activation. We hypothesized that these dissimilar effects on fetal HPA activity result from different influences of maternal glucocorticoid (GC) on maturation of the fetal HPA axis, mediated via different activities of placental 11β-hydroxysteroid dehydrogenase (11βHSD) isozymes. We examined the effects of twinning and maternal periconceptional UN from 60 days before until 30 days after mating on the ontogeny of placental 11βHSD-1 and -2 enzyme activities. At day 85 of gestation, placental 11βHSD-2 activity was lower in UN than in normally nourished (N) fetuses (P <.05) and was higher in twins than in singletons (P <.05). Furthermore, placental 11βHSD-1 activity was not different between nutritional groups but was higher in twins than in singletons (P = .01). At day 85, fetal plasma cortisol (P <.001) and cortisone (P <.001) concentrations were lower in UN than in N fetuses, but the cortisol to cortisone ratio was higher in UN than in N fetuses (P = .01). There was no effect of fetus number on plasma cortisol or cortisone concentrations or on the ratio of cortisol to cortisone at day 85. Therefore, periconceptional UN and twinning may result in the alterations of placental 11βHSD isozyme activities at particular times during gestation. Changes in these activities during critical periods of fetal development could affect transplacental transfer or placental generation of GCs that reach the fetus, potentially influencing the timing of activation of the fetal HPA axis, fetal maturation, and hence the development and health later in life.

    AB - Periconceptional undernutrition (UN) in sheep accelerates fetal hypothalamic-pituitary-adrenal (HPA) axis activation, resulting in preterm birth. In contrast, twin conception suppresses fetal HPA function and delays prepartum HPA activation. We hypothesized that these dissimilar effects on fetal HPA activity result from different influences of maternal glucocorticoid (GC) on maturation of the fetal HPA axis, mediated via different activities of placental 11β-hydroxysteroid dehydrogenase (11βHSD) isozymes. We examined the effects of twinning and maternal periconceptional UN from 60 days before until 30 days after mating on the ontogeny of placental 11βHSD-1 and -2 enzyme activities. At day 85 of gestation, placental 11βHSD-2 activity was lower in UN than in normally nourished (N) fetuses (P <.05) and was higher in twins than in singletons (P <.05). Furthermore, placental 11βHSD-1 activity was not different between nutritional groups but was higher in twins than in singletons (P = .01). At day 85, fetal plasma cortisol (P <.001) and cortisone (P <.001) concentrations were lower in UN than in N fetuses, but the cortisol to cortisone ratio was higher in UN than in N fetuses (P = .01). There was no effect of fetus number on plasma cortisol or cortisone concentrations or on the ratio of cortisol to cortisone at day 85. Therefore, periconceptional UN and twinning may result in the alterations of placental 11βHSD isozyme activities at particular times during gestation. Changes in these activities during critical periods of fetal development could affect transplacental transfer or placental generation of GCs that reach the fetus, potentially influencing the timing of activation of the fetal HPA axis, fetal maturation, and hence the development and health later in life.

    U2 - 10.1177/1933719109345162

    DO - 10.1177/1933719109345162

    M3 - Article

    VL - 16

    SP - 1201

    EP - 1212

    JO - Journal of the Society for Gynecologic Investigation

    JF - Journal of the Society for Gynecologic Investigation

    SN - 1071-5576

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