Oocyte polarity and cell determination in early mammalian embryos

Abstract

Knowledge on determination and differentiation in the mammalian embryo has not kept pace with discoveries in other phyla. Current concepts overlook well-established pathways leading to polarity in oocytes and embryos of other phyla, modern principles of totipotency in plants and animals, and axis formation in lower vertebrates. Various models derived from invertebrates and frogs could be relevant to the situation in eutherian mammals, and we explore the nature of strict genetic controls in these species and its implications for early mammalian differentiation. Concepts on totipotency and related phenomena in animal and human embryos are examined and the possibility raised that two cell lines are formed in early human embryos from the 2-4 cell stage. Clinical consequences are assessed, including causes of the high incidence of chromosomal mosaicism in human embryos. Our interpretations are obviously speculative, and must be clarified by experimentation.

Developmental capacity and pregnancy rate of tetrahedral- versus non-tetrahedral-shaped 4-cell stage human embryos

“…Hereby, the polarized ooplasm may be distributed in another way to the blastomeres of tetrahedral and non-tetrahedral 4-cell stage embryos [5,8,11]. Although at a lower level, non-tetrahedral-shaped embryos were able to form high-quality blastocysts and transfer of such blastocysts led to normal pregnancy rates.…”

“…Mammalian oocytes consist of an animal pole, marked by the second polar body and a vegetal pole on the opposite site [5][6][7][8]. The first meridional division occurs according to the animal-vegetal axis of the zygote [9,10].…”

“…Partitioning of the ooplasm may introduce developmentally significant asymmetries between the blastomeres at the 4-cell stage. In 1997, Edwards and Beard introduced a model of early cell determination [5]. They proposed that the two blastomeres inheriting animal and vegetal ooplasm are precursors of the inner cell mass (ICM), the blastomere inheriting mainly animal ooplasm is the precursor of the trophectoderm (TE) and the blastomere inheriting mainly vegetal ooplasm is the precursor of the germ line [5,8,11].…”

“…In 1997, Edwards and Beard introduced a model of early cell determination [5]. They proposed that the two blastomeres inheriting animal and vegetal ooplasm are precursors of the inner cell mass (ICM), the blastomere inheriting mainly animal ooplasm is the precursor of the trophectoderm (TE) and the blastomere inheriting mainly vegetal ooplasm is the precursor of the germ line [5,8,11]. This model of early asymmetry was extrapolated to the human and supported by the polarized distribution of proteins such as Leptin and STAT3 in the oocyte, their differential distribution between the blastomeres at the 4-cell stage and later on between the ICM and TE [6] and by the reciprocal expression of OCT-4 and βhCG transcripts at the 4-cell stage [11,12].…”

“…The early interpretation of Edwards's model that the generated differences would be deterministic proved wrong as early cells can change their fate after repositioning [14]. However, the altered orientation of the cleavage planes in non-tetrahedral-shaped embryos may cause aberrant distributions of animal and vegetal ooplasm, including cell organelles and maternally inherited transcripts and proteins, between the blastomeres [5,6]. Whether this affects the development and Non-tetrahedral-shaped embryos the implantation potential of non-tetrahedral-shaped 4-cell stage human embryos is unknown.…”