Single-cell multi-omic analysis profiles defective genome activation and epigenetic reprogramming associated with human pre-implantation embryo arrest.

During pre-implantation stages of mammalian development, maternally stored material promotes both the erasure of the sperm and oocyte epigenetic profiles and is responsible for concomitant genome activation. Here, we have utilized single-cell methylome and transcriptome sequencing (scM&T-seq) to quantify both mRNA expression and DNA methylation in oocytes and a developmental series of human embryos at single-cell resolution. We fully characterize embryonic genome activation and maternal transcript degradation and map key epigenetic reprogramming events in developmentally high-quality embryos. By comparing these signatures with early embryos that have undergone spontaneous cleavage-stage arrest, as determined by time-lapse imaging, we identify embryos that fail to appropriately activate their genomes or undergo epigenetic reprogramming. Our results indicate that a failure to successfully accomplish these essential milestones impedes the developmental potential of pre-implantation embryos and is likely to have important implications, similar to aneuploidy, for the success of assisted reproductive cycles.

Pronóstico reproductivo de las malformaciones müllerianas / Reproductive prognosis of Müllerian malformations

En un relativamente elevado porcentaje de loscasos en que se observan diferentescomplicaciones obstétricas en el embarazo, existealgún tipo de malformación mülleriana tras lacausa de estas complicaciones. Diferentes estudioshan tratado de establecer una incidencia de estasanomalías en la población con el fin de podertener un control más claro sobre su impactoreproductivo. Sin embargo, al hablar demalformaciones anatómicas en el tracto genitalfemenino nos encontramos ante una gran variedadde anomalías, en las cuales se observan diferentesgrados de impacto reproductivo, desde una granpropensión al aborto recurrente en diferentes fasesdel embarazo hasta casos en que las mujeresafectadas son completamente asintomáticas yfértiles. En esta revisión hablaremos acerca delpronóstico reproductivo que presentan lasdiferentes clases de malformaciones müllerianas, asícomo de su origen, diagnóstico y posiblestratamientos

A significant percentage of the patients withobstetric complications have a type of abnormalityknown as Müllerian malformations. Many studieshave tried to establish the incidence of theseabnormalities to determine their impact on humanreproduction.However, anatomical malformations of the femalegenital tract encompass a wide variety ofanomalies, with distinct impacts on reproduction,ranging from a high propensity to recurrentabortion in different phases of pregnancy to acomplete absence of symptoms and completefertility. The present review summarizes thereproductive prognosis of Müllerianmalformations, as well as the origin, diagnosisand treatment of these entities