Research progress on mosaic embryo transfer and pregnancy risk / 中华预防医学杂志

Mosaic embryos contain two or more genetically distinct cell lines, which can be detected by pre-implantation genetic testing for aneuploidy. At present, it has been reported that mosaic embryo transfer can lead to healthy live births. In order to prevent severe adverse pregnancy outcomes, such as implantation failure, abortion, congenital malformation and neonatal death after implantation of mosaic embryos, it is critical to carry out genetic counseling, prenatal diagnosis and pregnancy supervision for mosaic embryo transfer. This article reviews the selection of mosaic embryos, the pregnancy outcomes of mosaic embryo transfer, and the safety of offspring, in order to provide references for the clinical practice of mosaic embryo transfer.

Histochemical study of early embryo implantation in rats / Estudio histoquímico de la implantación temprana en ratas

Embryo implantation is the process that results in attachment of the conceptus to the uterine wall. In this histochemical study, we investigated the early stage of embryo implantation in rats by morphological analysis and by the detection of total proteins and glycosaminoglycans using hematoxylin-eosin, toluidine blue at pH 4.0 (TB), and Xylidine Ponceau at pH 2.5 (XP). In non-pregnant females, the uterine layers could be clearly distinguished and showed the normal histology of the organ. In pregnant females, an increase in the number of cells and a reduction in the interstitial space were observed in the endometrium close to the implantation sites. The blastocyst was partially inserted in the endometrium, with the observation of the inner cells mass around the blastocyst cavity surrounded by trophoblastic cells. TB staining revealed mild metachromatic basophilia, which was more evident in the endometrial stroma around the implantation site. Histochemical staining with XP was also more intense in the stroma close to the site of implantation. On the other hand, histochemical staining with either TB or XP was more discrete at sites distant from the conceptus. This study demonstrated changes in the endometrial stroma in areas adjacent to the site of embryo implantation, with variations in glycosaminoglycans and proteins as demonstrated by the detection of anionic and cationic radicals, respectively.

La implantación embrionaria es el proceso que resulta en la unión del embrión a la pared uterina. En este estudio histoquímico, se determinó la fase inicial de implantación del embrión en ratas mediante el análisis morfológico y por la detección de proteínas totales y glicosaminoglicanos con hematoxilina-eosina, azul de toluidina a pH 4,0 (TB) y xilidina Ponceau a un pH de 2,5 (XP). En las hembras no preñadadas, las capas del útero pueden ser claramente distinguidas y mostraron la histología normal del órgano. En las hembras preñadas, se observa un incremento en el número de células y una reducción en el espacio intersticial del endometrio para cerrar los sitios de implantación. El blastocisto se implanta parcialmente en el endometrio, con presencia de masa de células internas en torno a la cavidad del blastocisto, rodeado por las células trofoblásticas. La tinción TB reveló leve basofilia metacromática, lo cual fue más evidente en el estroma endometrial alrededor del sitio de implantación. Tinción histoquímica con XP también fue más intensa próximo del estroma en el sitio de implantación. Por otro lado, la tinción histoquímica, ya sea con la tuberculosis o XP fue más leve en los lugares distantes del embrión. Este estudio demostró cambios en el estroma del endometrio en las zonas adyacentes al sitio de la implantación del embrión, con variaciones en glucosaminoglicanos y proteínas, como lo demuestra la detección de radicales aniónicos y catiónicos, respectivamente.

DGP: técnica e indicaciones / PGD: technique and indications

El DGP (diagnóstico genético preimplantatorio), conocido también con las siglas del inglés PGD (preimplantation genetic diagnosis) es una herramienta más dentro del arsenal diagnóstico y terapéutico con que cuenta hoy la Medicina Asistencial. El diagnóstico genético efectuado con esta técnica puede involucrar diferentes alteraciones, tanto a nivel cromosómico como génico. El procedimiento se efectúa en los zigotos clivados obtenidos mediante las técnicas de Reproducción Asistida de Alta Complejidad, antes de la transferencia de los mismos al útero materno. Constituye una alternativa válida dentro de la metodología del diagnóstico prenatal, tendiente a identificar anomalías genéticas antes de la implantación del embrión. Pueden ser estudiadas alteraciones numéricas de los cromosomas sexuales, anomalías estructurales, enfermedades con herencia ligada al cromosoma X y enfermedades monogénicas. La aplicación de esta técnica también es especialmente importante en el área de la medicina reproductiva, debido a que es frecuente la asociación entre esterilidad y factores genéticos. Así, sus principales indicaciones serían la edad materna avanzada, las parejas con aborto a repetición o con fallo recurrente de implantación y el factor masculino severo. Para efectuar el DGP requiere previamente de la realización técnica de los procedimientos de Fecundación asistida, ya sea fecundacion in vitro (FIV) o por inyección intracitoplásmatica espermática (ICSI, según su sigla en inglés por Intracitoplasmatic Sperm Injection). Luego de la obtención de los embriones a través de dichas técnicas, se procede a la extracción del material que será objeto del estudio citogenético (cuerpos polares o una a dos blastómeras) en forma mecánica, química o física. El material a analizar podrá ser la biopsia del cuerpo polar (CP), la biopsia en estado de cigoto hasta mórula avanzada o la biopsia en estado de blastocito...

Fisiopatologia da pré-eclâmpsia: aspectos atuais / Physiopathology of pre-eclampsia: new insights

A pré-eclâmpsia, principal causa de morte materna no mundo, é conhecida como a doença das teorias. Nos últimos anos, diversos avanços no área médica permitiram aprofundar nossos conhecimentos sobre a sua etiopatogenia. Sabemos, atualmente, que fatores genéticos, como a interação entre HLA paterno e linfócitos NK maternos, estão envolvidos na origem da placentação deficiente, um dos principais fatores de risco da pré-eclâmpsia. Fatores imunológicos, como a falha do estabelecimento da reação inflamatória tipo 2 na implantação do embrião, também poderiam dificultar a invasão trofoblástica. O conceito de que a pré-eclâmpsia não é uma doença única, mas um conjunto de doenças com manifestações clínicas comuns veio para ajudar na elucidação do problema. A pré-eclâmpsia é considerada, hoje em dia, um estado imflamatório com disfunção endotelial sistêmica. Nesta revisão, os autores compilam as teorias mais recentes sobre a fisiopatologia dessa doença tão intrigante.

Pre-eclampsia, the leading cause of maternal death around the world, is also known as the disease of theories. Several developments in the last years allowed us to improve our knowledge over its etiopathogeny. It is known that genetic factors, as the interaction between paternal HLA antigens and maternal natural killer lynfocytes, are involved in the origin of incomplete placentation, one of the most powerful risk factors for the development of pre-eclampsia. Imunological factors, as the failure in the establishment of inflammatory Reaction type 2, at implantation time, could also difficult the trophoblastic invasion. The conception of pre-eclampsia as a group of diseases with a common set of clinical manifestations help us to further understand the problem. Pre-eclampsia is considered to be an inflammatory state with systemic endothelial dysfunction. In this review paper, the authors gather the most recent theories about the physiopathology of such intriguing disease.

No evidence of association of MUC-1 genetic polymorphism with embryo implantation failure

Pregnancy loss can be caused by several factors involved in human reproduction. Although up to 50 percent of cases remain unexplained, it has been postulated that the major cause of failed pregnancy is an error of embryo implantation. Transmembrane mucin-1 (MUC-1) is a glycoprotein expressed on the endometrial cell surface which acts as a barrier to implantation. The gene that codes for this molecule is composed of a polymorphic tandem repeat of 60 nucleotides. Our objective was to determine if MUC-1 genetic polymorphism is associated with implantation failure in patients with a history of recurrent abortion. The study was conducted on 10 women aged 25 to 35 years with no history of successful pregnancy and with a diagnosis of infertility. The control group consisted of 32 patients aged 25 to 35 years who had delivered at least two full-term live children and who had no history of abortions or fetal losses. MUC-1 amplicons were obtained by PCR and observed on agarose and polyacrylamide gel after electrophoresis. Statistical analysis showed no significant difference in the number of MUC-1 variable number of tandem repeats between these groups (P > 0.05). Our results suggest that there is no effect of the polymorphic MUC-1 sequence on the implantation failure. However, the data do not exclude MUC-1 relevance during embryo implantation. The process is related to several associated factors such as the mechanisms of gene expression in the uterus, specific MUC-1 post-translational modifications and appropriate interactions with other molecules during embryo implantation.

Transcription and translation of Dickkopf-1 in endometrium of pregnant mice during the peri-implantation period / 华中科技大学学报（医学）（英德文版）

To study the expression of Dickkopf-1 (DKK-1) in endometrium of pregnant mice during the peri-implantation period and the role of DKK-1 during the embryo implantation in mice. Immunohistochemical technique was employed to determine the location of DKK-1 protein in endometrium, and semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) was utilized to determine the levels of DKK-1 mRNA. Our results showed that the expressions of DKK1 mRNA and protein were higher in experimental groups than in control group (P<0.01) and it increased significantly on day 3 and reached its peak on day 4, and then decreased gradually on day 5-7. The levels of DKK-1 mRNA and protein on day 4 was significantly higher than those of other groups (P<0.01). It is concluded that DKK-1 probably plays an important role in signal transudation of embryo implantation and its high expression indicates the opening of implantation window.