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- Frygelius, J, et al.
(författare)
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The reproductive tissue specific cystatin subgroup of genes: expression during gonadal development in wildtype and testatin knockout animals
- 2007
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Ingår i: Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation. - : S. Karger AG. - 1661-5433. ; 1:6, s. 363-372
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Tidskriftsartikel (refereegranskat)abstract
- <i>Testatin</i> has been implicated in fetal testis development due to its restricted expression in pre-Sertoli cells immediately after the onset of <i>Sry</i> gene expression. However,<i> testatin</i> knockout mice showed normal testis development and fertility. We investigated the spatial and temporal expression pattern of the <i>Cres/testatin</i> subgroup of genes, including the novel gene <i>Cstl1/Cres4</i>, in fetal mouse gonads and in adult testis, epididymis and ovary. The genes are related to the family 2 cystatins of protease inhibitors. Using real-time PCR and in situ hybridization we could show that 4 subgroup genes, <i>testatin, CstSC, CstTE-1/Cres3</i> and <i>Cres</i> are expressed in fetal testis. We also confirmed the expression of <i>testatin, CstE2, CstSC, CstTE-1/Cr</i>es3, <i>Cres, CstT</i> and <i>Cstl1/Cres4</i> in adult testis and <i>CstE2, CstTE-1/Cres3, Cres</i> and <i>CstE1/Cres2</i> in adult epididymis. In <i>testatin </i>knockout animals, the expression of <i>CstE2</i> was heavily downregulated in adult testis, but not in adult epididymis, compared to wildtype controls. In conclusion, an explanation for the lack of phenotype in <i>testatin</i> knockout mice could be functional redundancy with another member of the <i>Cres/testatin</i> subgroup. The most likely candidate/s would be <i>CstSC, CstTE-1/Cres3</i> or <i>Cres</i> as they are expressed in the fetal testicular tubules in early testis differentiation together with <i>testatin.</i>
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- Hashimoto, K, et al.
(författare)
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Embryonic LTR retrotransposons supply promoter modules to somatic tissues
- 2021
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 31:11, s. 1983-1993
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Tidskriftsartikel (refereegranskat)abstract
- Long terminal repeat (LTR) retrotransposons are widely distributed across the human genome. They have accumulated through retroviral integration into germline DNA and are latent genetic modules. Active LTR promoters are observed in germline cells; however, little is known about the mechanisms underlying their active transcription in somatic tissues. Here, by integrating our previous transcriptome data set with publicly available data sets, we show that the LTR families MLT2A1 and MLT2A2 are primarily expressed in human four-cell and eight-cell embryos and are also activated in some adult somatic tissues, particularly pineal gland. Three MLT2A elements function as the promoters and first exons of the protein-coding genes ABCE1, COL5A1, and GALNT13 specifically in the pineal gland of humans but not in that of macaques, suggesting that the exaptation of these LTRs as promoters occurred during recent primate evolution. This analysis provides insight into the possible transition from germline insertion to somatic expression of LTR retrotransposons.
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- Jouhilahti, EM, et al.
(författare)
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The human PRD-like homeobox gene LEUTX has a central role in embryo genome activation
- 2016
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Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 143:19, s. 3459-3469
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Tidskriftsartikel (refereegranskat)abstract
- Leucine twenty homeobox gene (LEUTX) is a PAIRED (PRD)-like homeobox gene that is expressed nearly exclusively in human preimplantation embryos. We previously identified a novel transcription start site for the predicted human LEUTX gene based on the transcriptional analysis of human preimplantation embryos. The novel variant encodes a protein with a complete homeodomain. Here we provide a detailed description of the molecular cloning of the complete homeodomain-containing LEUTX. Using a human embryonic stem cell overexpression model we show that the complete homeodomain isoform is functional and sufficient to activate the transcription of a large fraction of the genes found upregulated in human embryo genome activation, whereas the previously predicted partial homeodomain isoform is largely inactive. Another PRD-like transcription factor, DPRX, appears as a powerful repressor of transcription. We propose a two-stage model of human EGA in which LEUTX acts as a transcriptional activator at 4-cell stage, and DPRX as a balancing repressor at 8-cell stage. We conclude that LEUTX is a candidate regulator of human embryo genome activation.
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- Madissoon, E, et al.
(författare)
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Characterization and target genes of nine human PRD-like homeobox domain genes expressed exclusively in early embryos
- 2016
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 28995-
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Tidskriftsartikel (refereegranskat)abstract
- PAIRED (PRD)-like homeobox genes belong to a class of predicted transcription factor genes. Several of these PRD-like homeobox genes have been predicted in silico from genomic sequence but until recently had no evidence of transcript expression. We found recently that nine PRD-like homeobox genes, ARGFX, CPHX1, CPHX2, DPRX, DUXA, DUXB, NOBOX, TPRX1 and TPRX2, were expressed in human preimplantation embryos. In the current study we characterized these PRD-like homeobox genes in depth and studied their functions as transcription factors. We cloned multiple transcript variants from human embryos and showed that the expression of these genes is specific to embryos and pluripotent stem cells. Overexpression of the genes in human embryonic stem cells confirmed their roles as transcription factors as either activators (CPHX1, CPHX2, ARGFX) or repressors (DPRX, DUXA, TPRX2) with distinct targets that could be explained by the amino acid sequence in homeodomain. Some PRD-like homeodomain transcription factors had high concordance of target genes and showed enrichment for both developmentally important gene sets and a 36 bp DNA recognition motif implicated in Embryo Genome Activation (EGA). Our data implicate a role for these previously uncharacterized PRD-like homeodomain proteins in the regulation of human embryo genome activation and preimplantation embryo development.
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- Salehnia, M, et al.
(författare)
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Does cryopreservation of ovarian tissue affect the distribution and function of germinal vesicle oocytes mitochondria?
- 2013
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Ingår i: BioMed research international. - : Hindawi Limited. - 2314-6141 .- 2314-6133. ; 2013, s. 489032-
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate mitochondrial alteration and ATP content of germinal vesicle (GV) oocytes isolated from fresh and vitrified ovaries. After superovulation, the ovaries from adult mice were collected and divided into control and vitrified groups. GV oocytes were isolated mechanically from each group. Half were cultured for 24 hours and their maturation was assessed. Metaphase II oocytes were collected and submitted toin vitrofertilization and their fertilization rates and development to the blastocyst stage were evaluated. In the remaining GV oocytes, ATP levels were quantified, and mitochondrial distribution, mitochondrial membrane potential, and intracellular free calcium were detected with rhodamine 123, JC-1 and Flou-4 AM staining, using laser-scanning confocal microscopy. Maturation and fertilization rates of GV oocytes and the developmental rates of subsequent embryos were significantly lower in vitrified samples (P<0.05). The ATP content and Ca2+levels differed significantly in fresh and vitrified GV oocytes (P<0.05). Most mitochondria were seen as large and homogenous aggregates (66.6%) in fresh GV oocytes compared to vitrified oocytes (50%). No significant differences in mitochondrial membrane potential were found between the groups. The lower maturation and fertilization rates of GV oocytes from vitrified ovaries may be due to changes in their mitochondrial function and distribution.
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- Tohonen, V, et al.
(författare)
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Novel PRD-like homeodomain transcription factors and retrotransposon elements in early human development
- 2015
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 8207-
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Tidskriftsartikel (refereegranskat)abstract
- Transcriptional program that drives human preimplantation development is largely unknown. Here, by using single-cell RNA sequencing of 348 oocytes, zygotes and single blastomeres from 2- to 3-day-old embryos, we provide a detailed analysis of the human preimplantation transcriptome. By quantifying transcript far 5′-ends (TFEs), we include in our analysis transcripts that derive from alternative promoters. We show that 32 and 129 genes are transcribed during the transition from oocyte to four-cell stage and from four- to eight-cell stage, respectively. A number of identified transcripts originates from previously unannotated genes that include the PRD-like homeobox genes ARGFX, CPHX1, CPHX2, DPRX, DUXA, DUXB and LEUTX. Employing de novo promoter motif extraction on sequences surrounding TFEs, we identify significantly enriched gene regulatory motifs that often overlap with Alu elements. Our high-resolution analysis of the human transcriptome during preimplantation development may have important implications on future studies of human pluripotent stem cells and cell reprograming.
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- Varshney, MK, et al.
(författare)
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Motor Function Deficits in the Estrogen Receptor Beta Knockout Mouse: Role on Excitatory Neurotransmission and Myelination in the Motor Cortex
- 2020
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 1423-0194 .- 0028-3835. ; 111:1-2, s. 27-44
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Male estrogen receptor beta (ERβ) knockout (BERKO) mice display anxiety and aggression linked to, among others, altered serotonergic signaling in the basolateral amygdala and dorsal raphe, impaired cortical radial glia migration, and reduced GABAergic signaling. The effects on primary motor cortex (M1 cortex) and locomotor activity as a consequence of ERβ loss have not been investigated. <b><i>Objective:</i></b> The aim of this study was to determine whether locomotor activity is altered as a consequence of the changes in the M1 cortex. <b><i>Methods:</i></b> The locomotor activity of male wild-type (WT) and BERKO mice was evaluated using the open-field and rotarod tests. Molecular changes in the M1 cortex were analyzed by RNA sequencing, electron microscopy, electrophysiology, and immunohistological techniques. In addition, we established oligodendrocyte (OL) cultures from WT and BERKO mouse embryonic stem cells to evaluate OL function. <b><i>Results:</i></b> Locomotor profiling revealed that BERKO mice were more active than WT mice but had impaired motor coordination. Analysis of the M1 cortex pointed out differences in synapse function and myelination. There was a reduction in GABAergic signaling resulting in imbalanced excitatory and inhibitory neurotransmission as well as a defective OL differentiation accompanied by myelin defects. The effects of ERβ loss on OL differentiation were confirmed in vitro. <b><i>Conclusion:</i></b> ERβ is an important regulator of GABAergic interneurons and OL differentiation, which impacts on adult M1 cortex function and may be linked to increased locomotor activity and decreased motor coordination in BERKO mice.
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