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The cooperative function of nuclear receptor coactivator 1 (NCOA1) and NCOA3 in placental development and embryo

Xian Chen1, Zhaoliang Liu, Jianming Xu

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.

Molecular Endocrinology (Baltimore, Md.)
|August 6, 2010
PubMed

Insights

Nuclear receptor coactivator 1 (NCOA1) and NCOA3 play crucial roles in placental development. Their combined absence leads to embryo death by E13.5, highlighting their cooperative function in embryo survival.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • Nuclear receptor coactivator 1 (NCOA1) and NCOA3 are key members of the steroid receptor coactivator (SRC) family.
  • While in vitro studies suggest overlapping functions, their in vivo relationship remains unclear.

Purpose of the Study:

  • To investigate the compensatory roles of NCOA1 and NCOA3 in embryonic development using a double knockout mouse model.
  • To elucidate the in vivo functional relationship between NCOA1 and NCOA3.

Main Methods:

  • Generation of NCOA1 and NCOA3 double knockout (DKO) mice.
  • Analysis of embryonic viability, placental morphology, and gene expression in wild-type, single-knockout, and DKO embryos.

Main Results:

  • NCOA1(-/-) mice survived normally, while NCOA3(-/-) embryos showed reduced viability by embryonic day 13.5 (E13.5).
  • DKO embryos exhibited significantly increased mortality by E13.5.
  • DKO placentas had smaller labyrinths with reduced maternal blood sinuses and fetal capillaries, abnormal trophoblast morphology, and altered expression of genes involved in placental morphogenesis and glucose transport.

Conclusions:

  • NCOA1 and NCOA3 are essential for normal placental development and embryo survival.
  • These coactivators cooperatively regulate placental morphogenesis, impacting trophoblast proliferation, differentiation, and vascularization.
  • Deficiencies in NCOA1 and NCOA3 disrupt critical pathways for placental function, leading to embryonic lethality.

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