A Subcortical Maternal Complex Essential for Preimplantation Mouse Embryogenesis

Abstract

SUMMARY We have identified a subcortical maternal complex (SCMC) that assembles during oocyte growth and is essential for zygotes to progress beyond the first embryonic cell divisions. At least four maternally encoded proteins contribute to this MDa complex: FLOPED, MATER and TLE6 interact with each other while Filia binds independently to MATER. Although the transcripts encoding these proteins are degraded during meiotic maturation and ovulation, the SCMC proteins persist in the early embryo. The SCMC, located in the subcortex of eggs, is excluded from regions of cell-cell contact in the cleavage-stage embryo and segregates to the outer cells of the morulae and blastocyst. Flopedtm/tm and/or Matertm/tm eggs lack the SCMC, but can be fertilized. However, these embryos do not progress beyond cleavage stage development and female mice are sterile. The proteins are conserved in humans and similar maternal effect mutations may result in recurrent embryonic loss.

Efectos de los RNAm maternos sobre la maduración del ovocito y el desarrollo embrionario temprano en mamíferos

“…El mantenimiento de la metilación de los ICRs, es punto clave para que el desarrollo embrionario ocurra de manera adecuada; en este proceso intervienen diversas proteínas, la mayoría de ellas con actividad de metiltransferasas y con un origen patterns of methylation in the early embryogenesis. Embryos whose gen was removed, have a total loss of methylation patterns and die on the zygote stage (10) .…”

“…Otro RNAm con efecto materno es zfp57, el cual codifica para un factor de transcripción requerido para el establecimiento de la metilación a nivel de la línea germinal y además participa en el mantenimiento de los patrones de metilación en la embriogénesis temprana. Embriones a los que se les eliminó este gen presentan una pérdida total de los patrones de metilación y mueren en la etapa de cigoto (10) .…”

“…De acuerdo a la experiencia de diversos grupos de investigación (7)(8)(9), en los sistemas bovinos, del total de ovocitos que se someten a maduración in vitro (IVM) sólo se logra obtener aproximadamente un 40 % de blastocistos viables; lo que es muy diferente a lo observado a partir de ovocitos madurados in vivo, donde el porcentaje de blastocistos viables obtenidos es cercano al 80 % . Esto sugiere que la IVM modifica el microambiente del ovocito, al ocasionar un cambio celular y genético que impide que esta célula se desarrolle de manera normal (10) . Desde folículo primordial hasta el folículo preantral, el ovocito almacena transcritos (11) , cuya traducción genera proteínas que son claves para su maduración (12) y, después de ser fertilizado, para su transición hacia el embrión (13) .…”

“…Posterior a esto, la membrana nuclear se rompe dando oportunidad para que los microtúbulos del huso mitótico se unan al and, at least in mice, are related to the progression of the zygote to 2-cell embryos. The proteins that make up this group are MATER (131) , FLOPED (10) , TLE6 (10) , FILIA (132) and PADI6 (133) . The absence of any of these proteins does not affect the ovarian follicle development or the development of germ cells; however, the absence of any of them, produces seemingly normal but infertile individuals, females produce eggs capable of being fertilized, but during embryonic development does not occur the maternal subcortical complex formation, and the phenotypes observed in embryos deficient of the genes that encode for some of these proteins, present arrests in 2-cell embryos (10,131,134,135) .…”

“…According to the experience of different research groups (7)(8)(9) in cattle systems, the total number of oocytes undergoing in vitro maturation (IVM) only manages to get about 40 % of the viable blastocysts; versus in vivo matured oocytes, where the percentage of viable blastocysts obtained is close to 80 %. This suggests that the IVM modifies the microenvironment of the oocyte, to cause cellular and genetic change that prevents this cell to develop as normal (10) . From primordial follicle until the preantral follicle the oocyte stores transcripts (11) , whose translation produces proteins that are key to its maturation (12) and, after being fertilized, for its transition to the embryo (13) .…”