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embryonic lethality before implantation

David Monk, Marta Sanchez-Delgado, Rosemary Fisher
Before activation of the embryonic genome, the oocyte provides many of the RNAs and proteins required for the epigenetic reprogramming and the transition to a totipotent state. Targeted disruption of a subset of oocyte-derived transcripts in mice results in early embryonic lethality and cleavage-stage embryonic arrest as highlighted by the members of the subcortical maternal complex (SCMC). Maternal-effect recessive mutations of NLRP7 , KHDC3L and NLRP5 in humans are associated with variable reproductive outcomes, biparental hydatidiform moles (BiHM) and widespread multi-locus imprinting disturbances...
December 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
Fernando H Biase, Chanaka Rabel, Michel Guillomot, Isabelle Hue, Kalista Andropolis, Colleen A Olmstead, Rosane Oliveira, Richard Wallace, Daniel Le Bourhis, Christophe Richard, Evelyne Campion, Aurélie Chaulot-Talmon, Corinne Giraud-Delville, Géraldine Taghouti, Hélène Jammes, Jean-Paul Renard, Olivier Sandra, Harris A Lewin
A major unresolved issue in the cloning of mammals by somatic cell nuclear transfer (SCNT) is the mechanism by which the process fails after embryos are transferred to the uterus of recipients before or during the implantation window. We investigated this problem by using RNA sequencing (RNA-seq) to compare the transcriptomes in cattle conceptuses produced by SCNT and artificial insemination (AI) at day (d) 18 (preimplantation) and d 34 (postimplantation) of gestation. In addition, endometrium was profiled to identify the communication pathways that might be affected by the presence of a cloned conceptus, ultimately leading to mortality before or during the implantation window...
December 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
Agnieszka Jedrusik, Andy Cox, Krzysztof B Wicher, David M Glover, Magdalena Zernicka-Goetz
The first lineage segregation in the mouse embryo generates the inner cell mass (ICM), which gives rise to the pluripotent epiblast and therefore the future embryo, and the trophectoderm (TE), which will build the placenta. The TE lineage depends on the transcription factor Cdx2. However, when Cdx2 first starts to act remains unclear. Embryos with zygotic deletion of Cdx2 develop normally until the late blastocyst stage leading to the conclusion that Cdx2 is important for the maintenance but not specification of the TE...
February 15, 2015: Developmental Biology
Manshu Tang, Anwer Siddiqi, Benjamin Witt, Tatiana Yuzyuk, Britt Johnson, Nisa Fraser, Wyman Chen, Rafael Rascon, Xue Yin, Harish Goli, Olaf A Bodamer, Kent Lai
The first GalT gene knockout (KO) mouse model for Classic Galactosemia (OMIM 230400) accumulated some galactose and its metabolites upon galactose challenge, but was seemingly fertile and symptom free. Here we constructed a new GalT gene-trapped mouse model by injecting GalT gene-trapped mouse embryonic stem cells into blastocysts, which were later implanted into pseudo-pregnant females. High percentage GalT gene-trapped chimera obtained were used to generate heterozygous and subsequently, homozygous GalT gene-trapped mice...
October 2014: European Journal of Human Genetics: EJHG
Florence Poulletier de Gannes, Bernard Billaudel, Emmanuelle Haro, Murielle Taxile, Laureline Le Montagner, Annabelle Hurtier, Saliha Ait Aissa, Hiroshi Masuda, Yann Percherancier, Gilles Ruffié, Philippe Dufour, Bernard Veyret, Isabelle Lagroye
In recent decades, concern has been growing about decreasing fecundity and fertility in the human population. Exposure to non-ionizing electromagnetic fields (EMF), especially radiofrequency (RF) fields used in wireless communications has been suggested as a potential risk factor. For the first time, we evaluated the effects of exposure to the 2450MHz Wi-Fi signal (1h/day, 6days/week) on the reproductive system of male and female Wistar rats, pre-exposed to Wi-Fi during sexual maturation. Exposure lasted 3 weeks (males) or 2 weeks (females), then animals were mated and couples exposed for 3 more weeks...
April 2013: Reproductive Toxicology
Ronald B Myers, Kibibi Rwayitare, Lauren Richey, Janis Lem, John J Castellot
CCN proteins play crucial roles in development, angiogenesis, cell motility, matrix turnover, proliferation, and other fundamental cell processes. Early embryonic lethality in CCN5 knockout and over-expressing mice led us to characterize CCN5 distribution in early development. Previous papers in this series showed that CCN5 is expressed widely in mice from E9.5 to adult; however, its distribution before E9.5 has not been studied. To fill this gap in our knowledge of CCN5 expression in mammals, RT-PCR was performed on preimplantation murine embryos: 1 cell, 2 cell, 4 cell, early morula, late morula, and blastocyst...
December 2012: Journal of Cell Communication and Signaling
Mahesh Mysore Shivananjappa, Muralidhara
Oxidative stress mechanisms have been implicated in congenital anomalies and morbidity/mortality of fetus/newborn in diabetic pregnancy. Numerous antioxidant treatments have shown varied beneficial effects in improving both maternal and fetal outcomes. The present study examined the propensity of taurine to attenuate the degree of embryopathy and oxidative stress among pregnant diabetic rats. Adult rats (CFT-Wistar) were rendered diabetic with an acute dose of streptozotocin (STZ; 45 mg/kg bodyweight) on gestation day (GD) 4...
May 2012: Reproductive Biomedicine Online
Xin He, Chen Sun, Feng Wang, Aijing Shan, Ting Guo, Weiqiong Gu, Bin Cui, Guang Ning
BACKGROUND: Members of the PPARγ coactivator-1 (PGC-1) family are central transcriptional coactivators that regulate cell metabolic processes ranging from mitochondrial biogenesis to oxidative respiration. PGC-1-related coactivator (PPRC1 or PRC), initially identified as a member of the PGC-1 family, is believed to regulate mitochondria biogenesis, respiration pathways, and cell proliferation. However, its physiological role is not clearly understood. Here, we investigate the biological functions of PPRC1 in vivo using PPRC1 deficient mice generated by gene targeting...
May 2012: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Han Jeong Lim, Yoon Jeon, Chang Hwan Jeon, Jong Hyun Kim, Ho Lee
Minichromosome maintenance 10 (MCM10) is a conserved, abundant nuclear protein, which plays a key role in the initiation of eukaryotic chromosomal DNA replication and elongation. To elucidate the physiological importance of MCM10 in vivo, we generated conventional knockout mice. No MCM10-null embryos were recovered after E8.5, and the mutation was found to be lethal before the implantation stage. Mutant embryos showed apparently normal growth until the morula stage, but growth defects after this stage. The dramatic reduction of 5-bromo-2-deoxyuridine (BrdU) incorporation in the mutant embryo, followed by cell death, suggests that defective cell proliferation may underlie this developmental failure...
October 2011: Biochimica et Biophysica Acta
H Chen, M J You, Y Jiang, W Wang, L Li
RMI1/BLAP75 (RecQ-mediated genome instability 1/Bloom-associated protein 75) is an OB-fold protein highly conserved from yeast to human. Previous studies showed that RMI1 is required for the stability of the BLM/RMI1/Top3α complex and for the suppression of elevated sister chromatids exchange (SCE). The presence of RMI1 strongly stimulates Holliday dissolution activity of the Bloom helicase in vitro. The in vivo function of RMI1, however, remains largely undefined. To address this question, we generated RMI1 knockout mice through homologous replacement targeting...
February 2011: Molecular Carcinogenesis
Luis C Fernandez-Diaz, Audrey Laurent, Sara Girasoli, Margherita Turco, Elena Longobardi, Giorgio Iotti, Nancy A Jenkins, Maria Teresa Fiorenza, Neal G Copeland, Francesco Blasi
Disruption of mouse Prep1, which codes for a homeodomain transcription factor, leads to embryonic lethality during post-implantation stages. Prep1(-/-) embryos stop developing after implantation and before anterior visceral endoderm (AVE) formation. In Prep1(-/-) embryos at E6.5 (onset of gastrulation), the AVE is absent and the proliferating extra-embryonic ectoderm and epiblast, marked by Bmp4 and Oct4, respectively, are reduced in size. At E.7.5, Prep1(-/-) embryos are small and very delayed, showing no evidence of primitive streak or of differentiated embryonic lineages...
October 2010: Development
Jinzhe Mao, David M McKean, Sunita Warrier, Joshua G Corbin, Lee Niswander, Irene E Zohn
Neural tube defects (NTDs) are some of the most common birth defects observed in humans. The incidence of NTDs can be reduced by peri-conceptional folic acid supplementation alone and reduced even further by supplementation with folic acid plus a multivitamin. Here, we present evidence that iron maybe an important nutrient necessary for normal development of the neural tube. Following implantation of the mouse embryo, ferroportin 1 (Fpn1) is essential for the transport of iron from the mother to the fetus and is expressed in the visceral endoderm, yolk sac and placenta...
September 2010: Development
Dolores Busso, Calixto Dominguez, Tomas Perez-Acle, Ricardo D Moreno
Caspases, cystein proteases traditionally related to programmed cell death, have recently been found to be involved in vital processes such as cell proliferation, adhesion and differentiation. Although caspases are expressed in mouse embryos before the blastocyst stage, their role is unclear, since apoptosis does not occur significantly before implantation. In this work, we have used mouse preimplantation development as a model to evaluate the existence of non-lethal caspase activities. The use of specific caspase inhibitors during in vitro embryo culture showed that caspase 8 activity, but not caspase 2 or 9, was relevant for development...
2010: International Journal of Developmental Biology
Tobias Goller, Franz Vauti, Suresh Ramasamy, Hans-Henning Arnold
The putative transcriptional regulator BPTF/FAC1 is expressed in embryonic and extraembryonic tissues of the early mouse conceptus. The extraembryonic trophoblast lineage in mammals is essential to form the fetal part of the placenta and hence for the growth and viability of the embryo in utero. Here, we describe a loss-of-function allele of the BPTF/FAC1 gene that causes embryonic lethality in the mouse. BPTF/FAC1-deficient embryos form apparently normal blastocysts that implant and develop epiblast, visceral endoderm, and extraembryonic ectoderm including trophoblast stem cells...
November 2008: Molecular and Cellular Biology
Norimasa Iwanami, Tomokazu Higuchi, Yumi Sasano, Toshinobu Fujiwara, Vu Q Hoa, Minoru Okada, Sadiqur R Talukder, Sanae Kunimatsu, Jie Li, Fumi Saito, Chitralekha Bhattacharya, Angabin Matin, Takashi Sasaki, Nobuyoshi Shimizu, Hiroshi Mitani, Heinz Himmelbauer, Akihiro Momoi, Hisato Kondoh, Makoto Furutani-Seiki, Yousuke Takahama
The thymus is a vertebrate-specific organ where T lymphocytes are generated. Genetic programs that lead to thymus development are incompletely understood. We previously screened ethylnitrosourea-induced medaka mutants for recessive defects in thymus development. Here we report that one of those mutants is caused by a missense mutation in a gene encoding the previously uncharacterized protein WDR55 carrying the tryptophan-aspartate-repeat motif. We find that WDR55 is a novel nucleolar protein involved in the production of ribosomal RNA (rRNA)...
August 29, 2008: PLoS Genetics
Rolf Schulte-Hermann, Gerald N Wogan, Colin Berry, Nigel A Brown, Andrew Czeizel, Erminio Giavini, Lewis B Holmes, Robert Kroes, Heinz Nau, Diether Neubert, Franz Oesch, Tilmann Ott, Olavi Pelkonen, Elisabeth Robert-Gnansia, Frank M Sullivan
CONCLUSION REGARDING CLASSIFICATION OF GLUFOSINATE-AMMONIUM: Science Partners' Evaluation Group (Evaluation Group) has conducted an independent analysis of the herbicide glufosinate-ammonium (GA) relative to its potential to cause reproductive toxicity in humans. Further, the Evaluation Group has evaluated the implementation of Annex 6 of Commission Directive 2001/59/EC (28th ATP of Council Directive 67/548/EEC) and Council Directive 91/414/EEC, with respect to classification of chemicals posing potential reproductive hazards...
April 2006: Regulatory Toxicology and Pharmacology: RTP
Zhining Den, Xing Cheng, Maria Merched-Sauvage, Peter J Koch
Desmocollin 3 (Dsc3) is a transmembrane glycoprotein that belongs to the cadherin family of cell adhesion receptors. Together with desmoglein(s), it forms the transmembrane core of desmosomes, a multiprotein complex involved in cell adhesion, organization of the cytoskeleton, cell sorting and cell signaling. Previous reports have suggested that Dsc3 synthesis is largely restricted to stratified epithelia, and that it plays a role in the proper differentiation of these tissues during mammalian embryonic development...
February 1, 2006: Journal of Cell Science
Katsutaka Miura, Kumiko Yoshinobu, Takashi Imaizumi, Kyoko Haruna, Yoichi Miyamoto, Yoshihiro Yoneda, Naomi Nakagata, Masatake Araki, Taihei Miyakawa, Ken-ichi Yamamura, Kimi Araki
Importin beta1 (Impbeta)/karyopherin beta1 (Kpnb1) mediates the nuclear import of a large variety of substrates. This study aimed to investigate the requirement for the Kpnb1 gene in mouse development, using a gene trap line, B6-CB-Ayu8108(GtgeoIMEG) (Ayu8108(geo)), in which the trap vector was inserted into the promoter region of the Kpnb1 gene, but in reverse orientation of the Kpnb1 gene. Ayu8108(geo/geo) homozygous embryos could develop to the blastocyst stage, but died before embryonic day 5.5, and expression of the Kpnb1 gene in homozygous blastocysts was undetectable...
March 3, 2006: Biochemical and Biophysical Research Communications
Yufen Xie, Yingchun Wang, Tong Sun, Fangfei Wang, Anna Trostinskaia, Elizabeth Puscheck, Daniel A Rappolee
Mitogen-activated protein kinase (MAPK) signaling pathways play an important role in controlling embryonic proliferation and differentiation. It has been demonstrated that sequential lipophilic signal transduction mediators that participate in the MAPK pathway are null post-implantation lethal. It is not clear why the lethality of these null mutants arises after implantation and not before. One hypothesis is that the gene product of these post-implantation lethal null mutants are not present before implantation in normal embryos and do not have function until after implantation...
May 2005: Molecular Reproduction and Development
Susanne C Bleckmann, Julie A Blendy, Dorothea Rudolph, A Paula Monaghan, Wolfgang Schmid, Günther Schütz
Activating transcription factor 1 (ATF1), CREB, and the cyclic AMP (cAMP) response element modulatory protein (CREM), which constitute a subfamily of the basic leucine zipper transcription factors, activate gene expression by binding as homo- or heterodimers to the cAMP response element in regulatory regions of target genes. To investigate the function of ATF1 in vivo, we inactivated the corresponding gene by homologous recombination. In contrast to CREB-deficient mice, which suffer from perinatal lethality, mice lacking ATF1 do not exhibit any discernible phenotypic abnormalities...
March 2002: Molecular and Cellular Biology
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