Regulation of Fetal-Placental Development in the Primate

Summary

Principal Investigator: EUGENE ALBRECHT
Affiliation: University of Maryland
Country: USA
Abstract: The high incidence of human neonatal morbidity and mortality associated with low birth weight and prematurity indicates need for more intensive study of the mechanisms underlying placental and fetal development. The long-term objective of this research proposal is to improve knowledge in this area by building on our previous in vivo studies in the pregnant baboon which demonstrate that estrogen plays an integrative role in placental-fetal communication by regulating maturation of the placenta and fetal adrenal gland. Study I will test the hypothesis that early in gestation estrogen stimulates vascular endothelial growth/permeability factor and/or angiopoietin-1/-2 formation by villous trophoblasts and thus placental angiogenesis, and concurrently regulates expression of integrins-adhesion molecules by extravillous cytotrophoblasts to restrain their invasion of uterine spiral arteries, and that via these actions estrogen coordinates angiogenesis and placentation to ensure fetal-placental development. The goals of Studies I and II are interwoven to test the hypothesis that estrogen acts on the newly vascularized placenta to regulate expression of sodium-hydrogen exchangers (NHE-1 and -3) and their regulatory factors in the syncytiotrophoblast, directly (NHE-1), and indirectly by regulating the 11beta-hydroxysteroid dehydrogenase enzymes and thus local cortisol levels (NHE-3) to ensure placental-fetal homeostasis. Studies II and III are integrated to test the hypothesis that estrogen acts on the fetal adrenal to promote development of the transitional zone and restrain growth and development of the fetal zone, and that this in utero programming governs adrenal maturation and function in adulthood. Molecular, histological, biochemical, and in vivo physiological parameters of placental trophoblast and fetal adrenal development will be determined in baboons in which estrogen levels are prematurely elevated by estradiol administration or suppressed by a specific aromatase inhibitor. The estrogen-depleted/-repleted pregnant baboon provides a unique primate model to investigate the effects of altered trophoblast function on fetal-neonatal maturation, studies which cannot be performed in pregnant women or with in vitro approaches. Completion of the proposed study will provide new insight into communication between the fetus and placenta and improve our knowledge of the regulation of fetal development and neonatal self-sufficiency.
Funding Period: 1980-07-01 - 2007-06-30
more information: NIH RePORT

Top Publications

  1. ncbi Estrogen elicits cortical zone-specific effects on development of the primate fetal adrenal gland
    Eugene D Albrecht
    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Bressler Research Laboratories 11 019, 655 West Baltimore Street, Baltimore, Maryland 21201, USA
    Endocrinology 146:1737-44. 2005
  2. pmc Regulation of baboon fetal pituitary prolactin expression by estrogen
    Gerald J Pepe
    Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23501 1980, USA
    Biol Reprod 80:1189-95. 2009
  3. pmc Impact of estradiol on gamma-aminobutyric acid- and glutamate-mediated calcium responses of fetal baboon (Papio anubis) hippocampal and cortical neurons
    Joseph L Nunez
    Department of Physiology, University of Maryland, Baltimore, Baltimore, Maryland 21201, USA
    Endocrinology 149:6433-43. 2008
  4. pmc Suppression of extravillous trophoblast vascular endothelial growth factor expression and uterine spiral artery invasion by estrogen during early baboon pregnancy
    Thomas W Bonagura
    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Bressler Research Laboratories 11 019, 655 West Baltimore Street, Baltimore, Maryland 21201, USA
    Endocrinology 149:5078-87. 2008
  5. pmc Regulation of placental villous angiopoietin-1 and -2 expression by estrogen during baboon pregnancy
    Eugene D Albrecht
    Department of Obstetrics, Center for Studies in Reproduction, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
    Mol Reprod Dev 75:504-11. 2008
  6. pmc Placental villous vascular endothelial growth factor expression and vascularization after estrogen suppression during the last two-thirds of baboon pregnancy
    Victoria A Robb
    Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Studies in Reproduction, University of Maryland School of Medicine, Baltimore, MD, USA
    Endocrine 31:260-7. 2007
  7. pmc Regulation of expression and localisation of the Na+/H+ exchanger (NHE) 3 and the NHE regulatory factor 2 in baboon placental syncytiotrophoblast by oestrogen
    G J Pepe
    Department of Physiological Sciences, Eastern Virginia Medical School, P O Box 1980, Norfolk, VA 23501 1980, USA
    Placenta 28:878-88. 2007
  8. ncbi Developmental expression of cell cycle regulators in the baboon fetal adrenal gland
    Adina Dumitrescu
    Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Studies in Reproduction, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    J Endocrinol 192:237-47. 2007
  9. pmc Differential expression of placental villous angiopoietin-1 and -2 during early, mid and late baboon pregnancy
    J S Babischkin
    Department of Obstetrics, Gynecology, Reproductive Sciences, Center for Studies in Reproduction, University of Maryland, School of Medicine, Baltimore, MD 21201, USA
    Placenta 28:212-8. 2007
  10. ncbi Developmental regulation of the sodium/hydrogen ion exchangers and their regulatory factors in baboon placental syncytiotrophoblast
    Gerald J Pepe
    Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23501 1980, USA
    Endocrinology 147:2986-96. 2006

Scientific Experts

  • EUGENE ALBRECHT
  • G J Pepe
  • Joseph Nunez
  • Graham W Aberdeen
  • Thomas W Bonagura
  • J S Babischkin
  • Adina Dumitrescu
  • Victoria A Robb
  • Marcia G Burch
  • Ahmet A Baschat
  • Chris R Harman
  • Patricia W Langenberg
  • Carl P Weiner
  • Allen C Enders
  • D L Suresch
  • Frank A Lattanzio
  • Anca D Dobrian

Detail Information

Publications13

  1. ncbi Estrogen elicits cortical zone-specific effects on development of the primate fetal adrenal gland
    Eugene D Albrecht
    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Bressler Research Laboratories 11 019, 655 West Baltimore Street, Baltimore, Maryland 21201, USA
    Endocrinology 146:1737-44. 2005
    ....
  2. pmc Regulation of baboon fetal pituitary prolactin expression by estrogen
    Gerald J Pepe
    Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23501 1980, USA
    Biol Reprod 80:1189-95. 2009
    ....
  3. pmc Impact of estradiol on gamma-aminobutyric acid- and glutamate-mediated calcium responses of fetal baboon (Papio anubis) hippocampal and cortical neurons
    Joseph L Nunez
    Department of Physiology, University of Maryland, Baltimore, Baltimore, Maryland 21201, USA
    Endocrinology 149:6433-43. 2008
    ..Along with documenting a prominent role for 17beta-estradiol in maturation of the GABAergic system, these findings increase our understanding of neuronal differentiation and maturation in the fetal primate brain...
  4. pmc Suppression of extravillous trophoblast vascular endothelial growth factor expression and uterine spiral artery invasion by estrogen during early baboon pregnancy
    Thomas W Bonagura
    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Bressler Research Laboratories 11 019, 655 West Baltimore Street, Baltimore, Maryland 21201, USA
    Endocrinology 149:5078-87. 2008
    ..We suggest that VEGF mediates the decline in EVT vessel invasion induced by estrogen in early primate pregnancy...
  5. pmc Regulation of placental villous angiopoietin-1 and -2 expression by estrogen during baboon pregnancy
    Eugene D Albrecht
    Department of Obstetrics, Center for Studies in Reproduction, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
    Mol Reprod Dev 75:504-11. 2008
    ..We propose that the estrogen-dependent differential regulation of these angioregulatory factors underpins the unique pattern of neovascularization established within the villous placenta during primate pregnancy...
  6. pmc Placental villous vascular endothelial growth factor expression and vascularization after estrogen suppression during the last two-thirds of baboon pregnancy
    Victoria A Robb
    Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Studies in Reproduction, University of Maryland School of Medicine, Baltimore, MD, USA
    Endocrine 31:260-7. 2007
    ....
  7. pmc Regulation of expression and localisation of the Na+/H+ exchanger (NHE) 3 and the NHE regulatory factor 2 in baboon placental syncytiotrophoblast by oestrogen
    G J Pepe
    Department of Physiological Sciences, Eastern Virginia Medical School, P O Box 1980, Norfolk, VA 23501 1980, USA
    Placenta 28:878-88. 2007
    ....
  8. ncbi Developmental expression of cell cycle regulators in the baboon fetal adrenal gland
    Adina Dumitrescu
    Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Studies in Reproduction, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    J Endocrinol 192:237-47. 2007
    ....
  9. pmc Differential expression of placental villous angiopoietin-1 and -2 during early, mid and late baboon pregnancy
    J S Babischkin
    Department of Obstetrics, Gynecology, Reproductive Sciences, Center for Studies in Reproduction, University of Maryland, School of Medicine, Baltimore, MD 21201, USA
    Placenta 28:212-8. 2007
    ....
  10. ncbi Developmental regulation of the sodium/hydrogen ion exchangers and their regulatory factors in baboon placental syncytiotrophoblast
    Gerald J Pepe
    Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23501 1980, USA
    Endocrinology 147:2986-96. 2006
    ..We conclude that the subcellular distribution and levels of key components of the Na+/H+ system in the baboon syncytiotrophoblast are developmentally regulated...
  11. ncbi Suppression of extravillous trophoblast invasion of uterine spiral arteries by estrogen during early baboon pregnancy
    E D Albrecht
    Department of Obstetrics, Center for Studies in Reproduction, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Placenta 27:483-90. 2006
    ..Consequently, we propose that the estrogen-dependent restraint of spiral artery invasion/remodeling ensures optimal blood flow dynamics across the uteroplacental vascular bed to promote normal fetal growth and development...
  12. ncbi Development of a coculture system and use of confocal laser fluorescent microscopy to study human microvascular endothelial cell and mural cell interaction
    Marcia G Burch
    Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    Microvasc Res 70:43-52. 2005
    ..We propose that this system will greatly facilitate study of remodeling of the microvasculature in various organ systems...
  13. pmc Uterine and fetal blood flow indexes and fetal growth assessment after chronic estrogen suppression in the second half of baboon pregnancy
    Graham W Aberdeen
    Dept of Obstetrics, Gynecology and Reproductive Sciences, Univ of Maryland School of Medicine, Baltimore, MD 21201, USA
    Am J Physiol Heart Circ Physiol 298:H881-9. 2010
    ..This suggests that elevated levels of endogenous estrogen are not required to maintain low impedance blood flow within the uteroplacental vascular bed during the second half of nonhuman primate pregnancy...