Molecular Human Reproduction, Vol 3, 1067-1086, Copyright © 1997 by Oxford University Press
M Antczak and J Van Blerkom
Unique protein domains, concentration gradients, and asymmetric protein
distributions or polarities are principle forces establishing the identity
and fate of individual cells during early development in lower vertebrates
and invertebrates. Here, we present evidence that these same forces exist
during mammalian development in the form of two representative regulatory
proteins, leptin and STAT3. Leptin, the 16 kDa cytokine product of the
obese gene (ob) is involved in the activation of STAT3, a member of the
signal transducer and activation of transcription family of proteins. We
examined the temporal and spatial aspects of leptin and STAT3
immunofluorescence in mouse and human oocytes and preimplantation stage
embryos. The findings demonstrate that both leptin and STAT3 are polarized
in the oocyte and, as a consequence of their location and the position of
the cleavage planes with respect to these protein domains: (i) differences
in allocation of these proteins between blastomeres occur at the first cell
division such that by the 8-cell stage; (ii) unique cellular domains
consisting of leptin/STAT3 rich and leptin/STAT3 poor populations of cells
are generated. By the morula stage, a cell-borne concentration gradient of
these proteins extending along the surface of the embryo is observed. A
potential role of these proteins in early development is indicated at the
morula stage where the 'inner' cells consist of blastomeres that contain
little, if any, leptin/STAT3 while 'outer' cells contain both leptin/STAT3
rich and poor cells. This pattern persists through the hatched blastocyst
stage with little, if any, leptin/STAT3 detected in the inner cell mass and
populations of leptin/STAT3 rich and poor cells forming the trophoblast. We
have examined oocytes from mutant C57BL/6J ob/ob mice which are both obese
and infertile (although fertility can be restored by the exogenous
provision of leptin) and have found STAT3 and the mutant (truncated) leptin
protein to be present and polarized, suggesting the possibility that the
truncated leptin protein may still contain operational domains which are
functional during oocyte development and early embryogenesis. Furthermore,
analysis of leptin and STAT3 in intact ovarian follicles suggests that
these proteins may be maternally derived and in particular, that a
subpopulation of follicle cells may be partly responsible for the
establishment of their polarized distribution in the oocyte. The results
are discussed with respect to the proposition that leptin and STAT3 have
critical roles in early mammalian development, and may be involved in the
determination of the animal pole of the oocyte and in the establishment of
the inner cell mass and trophoblast in the preimplantation stage embryo.
JOURNAL ARTICLE
Oocyte influences on early development: the regulatory proteins leptin and STAT3 are polarized in mouse and human oocytes and differentially distributed within the cells of the preimplantation stage embryo
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder 80309, USA.
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