Journal article
Opioid and Progesterone Signaling is Obligatory for Early Human Embryogenesis
Stem cells and development, Vol.18(5), pp.737-740
09/19/2008
DOI: 10.1089/scd.2008.0190
PMCID: PMC2891507
PMID: 18803462
Abstract
The growth factors that drive the division and differentiation of stem cells during early human embryogenesis are unknown. The secretion of endorphins, progesterone (P
4
), human chorionic gonadotropin, 17β-estradiol, and gonadotropin-releasing hormone by trophoblasts that lie adjacent to the embryoblast in the blastocyst suggests that these pregnancy-associated factors may directly signal the growth and development of the embryoblast. To test this hypothesis, we treated embryoblast-derived human embryonic stem cells (hESCs) with ICI 174,864, a δ-opioid receptor antagonist, and RU-486 (mifepristone), a P
4
receptor competitive antagonist. Both antagonists potently inhibited the differentiation of hESC into embryoid bodies, an in vitro structure akin to the blastocyst containing all three germ layers. Furthermore, these agents prevented the differentiation of hESC aggregates into columnar neuroectodermal cells and their organization into neural tube-like rosettes as determined morphologically. Immunoblot analyses confirmed the obligatory role of these hormones; both antagonists inhibited nestin expression, an early marker of neural precursor cells normally detected during rosette formation. Conversely, addition of P
4
to hESC aggregates induced nestin expression and the formation of neuroectodermal rosettes. These results demonstrate that trophoblast-associated hormones induce blastulation
and
neurulation during early human embryogenesis.
Details
- Title: Subtitle
- Opioid and Progesterone Signaling is Obligatory for Early Human Embryogenesis
- Creators
- Miguel J. Gallego - University of Wisconsin–MadisonPrashob Porayette - University of Wisconsin and Geriatric ResearchMaria M. Kaltcheva - University of Wisconsin and Geriatric ResearchSivan Vadakkadath Meethal - University of Wisconsin and Geriatric ResearchCraig S. Atwood - Case Western Reserve University
- Resource Type
- Journal article
- Publication Details
- Stem cells and development, Vol.18(5), pp.737-740
- Publisher
- Mary Ann Liebert, Inc
- DOI
- 10.1089/scd.2008.0190
- PMID
- 18803462
- PMCID
- PMC2891507
- ISSN
- 1547-3287
- eISSN
- 1557-8534
- Language
- English
- Date published
- 09/19/2008
- Academic Unit
- Cardiology; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984353840702771
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