Genome stability of bovine in vivo-conceived cleavage-stage embryos is higher compared to in vitro-produced embryos.

STUDY QUESTION Is the rate and nature of chromosome instability (CIN) similar between bovine in vivo-derived and in vitro-cultured cleavage-stage embryos? SUMMARY ANSWER There is a major difference regarding chromosome stability of in vivo-derived and in vitro-cultured embryos, as CIN is significantly lower in in vivo-derived cleavage-stage embryos compared to in vitro-cultured embryos. WHAT IS KNOWN ALREADY CIN is common during in vitro embryogenesis and is associated with early embryonic loss in humans, but the stability of in vivo-conceived cleavage-stage embryos remains largely unknown. STUDY DESIGN, SIZE, DURATION Because human in vivo preimplantation embryos are not accessible, bovine (Bos taurus) embryos were used to study CIN in vivo. Five young, healthy, cycling Holstein Friesian heifers were used to analyze single blastomeres of in vivo embryos, in vitro embryos produced by ovum pick up with ovarian stimulation (OPU-IVF), and in vitro embryos produced from in vitro matured oocytes retrieved without ovarian stimulation (IVM-IVF). PARTICIPANTS/MATERIALS, SETTING, METHODS Single blastomeres were isolated from embryos, whole-genome amplified and hybridized on Illumina BovineHD BeadChip arrays together with the bulk DNA from the donor cows (mothers) and the bull (father). DNA was also obtained from the parents of the bull and from the parents of the cows (paternal and maternal grandparents, respectively). Subsequently, genome-wide haplotyping and copy-number profiling was applied to investigate the genomic architecture of 171 single bovine blastomeres of 16 in vivo, 13 OPU-IVF and 13 IVM-IVF embryos. MAIN RESULTS AND THE ROLE OF CHANCE The genomic stability of single blastomeres in both of the in vitro-cultured embryo cohorts was severely compromised (P < 0.0001), and the frequency of whole chromosome or segmental aberrations was higher in embryos produced in vitro than in embryos derived in vivo. Only 18.8% of in vivo-derived embryos contained at least one blastomere with chromosomal anomalies, compared to 69.2% of OPU-IVF embryos (P < 0.01) and 84.6% of IVM-IVF embryos (P < 0.001). LARGE SCALE DATA Genotyping data obtained in this study has been submitted to NCBI Gene Expression Omnibus (GEO; accession number GSE95358) LIMITATIONS REASONS FOR CAUTION There were two main limitations of the study. First, animal models may not always reflect the nature of human embryogenesis, although the use of an animal model to investigate CIN was unavoidable in our study. Second, a limited number of embryos were obtained, therefore more studies are warranted to corroborate the findings. WIDER IMPLICATIONS OF THE FINDINGS Although CIN is also present in in vivo-developed embryos, in vitro procedures exacerbate chromosomal abnormalities during early embryo development. Hence, the present study highlights that IVF treatment compromises embryo viability and should be applied with care. Additionally, our results encourage to refine and improve in vitro culture conditions and assisted reproduction technologies. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by the Agency for Innovation by Science and Technology (IWT) (TBM-090878 to J.R.V. and T.V.), the Research Foundation Flanders (FWO; G.A093.11 N to T.V. and J.R.V. and G.0392.14 N to A.V.S. and J.R.V.), the European Union's FP7 Marie Curie Industry-Academia Partnerships and Pathways (IAPP, SARM, EU324509 to J.R.V., T.V., O.T, A.D., A.S. and A.K.) and Horizon 2020 innovation programme (WIDENLIFE, 692065 to J.R.V., O.T., T.V., A.K. and A.S.). M.Z.E., J.R.V. and T.V. are co-inventors on a patent application ZL913096-PCT/EP2014/068315-WO/2015/028576 (‘Haplotyping and copy-number typing using polymorphic variant allelic frequencies’), licensed to Cartagenia (Agilent Technologies

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Meisterlikud õpipoisid. Jaan Kaplinski ja tema hingesugulane Tomas Tranströmer / Masterful Servants: Jaan Kaplinski and his soulmate Tomas Tranströmer

Luuletajad Jaan Kaplinski (1941–2021) ja Tomas Tranströmer (1931–2015), keda lahutas raudne eesriie, kasvasid üles väga erinevates maailmades. Ent siiski said neist hingesugulased. Artiklis osutan, kuidas nende läheduse tuuma iseloomustas sügavalt juurdunud hoiak, mis põhines ökoloogiast inspireeritud maailmatunnetusel. Tugevasti lihtsustades võiks öelda, et oma egosse investeerimise asemel nägid mõlemad luuletajad end millegi suurema teenritena. Nad hindasid mõlemad kõrgelt avatuks jäävat vaadet enestele, oma tööle ja maailmale, millesse nad kuulusid. Kui nende egod viibisid pidevas taandumises, avardus nende vastuvõtlikkus maailma suhtes ning köitvus luuletajatena. --- Separated by the Iron Curtain, Jaan Kaplinski (1941–2021) and Tomas Tranströmer (1931–2015) grew up in very different worlds. And yet, they became soulmates. What then informed the core of their kinship? This article aims to show that it was above all a deeply rooted sentiment grounded in an ecologically inspired view that brought the two poets together. To put a complex matter all too simply, Jaan Kaplinski and Tomas Tranströmer saw themselves as servants of something bigger: they shared a profoundly felt sense of “openness,” something which also lies at the heart of their success as poets. In Jaan Kaplinski’s and Tomas Tranströmer’s work and habits of thought, this core sentiment left easily overlooked but nevertheless telling traces. They include, as this article points out, their conversation concerning the translation of an essential term in Eastern thought, namely śūnyatā (emptiness). Tranströmer followed Kaplinski’s unique suggestion, which was meant to capture more of the essence and spirit inherent in the term śūnyatā. As a consequence, in the final version of one of his best-known poems, entitled “Vermeer”, Tranströmer changed to “openness” what in Buddhism is commonly referred to as “emptiness”. &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Yet probably more significantly, what above all held Kaplinski and Tranströmer captive, as this article also aims to show, is a reversal in our understanding of the ego. Collectively, both poets agreed, we, as human beings, would be well advised to embrace a less intrusive role in the world to which we belong. Importantly, what Kaplinski and Tranströmer advocated does not amount to an impoverishing stance. On the contrary: only when we step away from our previous deeply entrenched positions of human dominance, both poets agreed, a richer world and more sustainable sense of self can come into view. To at least gain a glimpse of the fuller complexity of what brought both poets together, the observations offered in this article are meant to help us understand how, for Kaplinski and Tranströmer, changes in our view of the ego embody “openness”. Instead of increased ego noise, they urged the merit of a more modest ego. Not preoccupied with themselves, their goals and desire to intervene, both poets wrote poems focussed on the diminished ego as a key value. The more we step into the background – Kaplinski and, together with him, Tranströmer believed – the more the world opens up and the more we ultimately flourish. In addition to seeing “openness” surface in their self-effacing view of themselves, and, associated with it, their concentration on a vision of a world beyond human design, this article furthermore draws attention to another equally prominent manifestation of “openness” that brought both poets together: how can language make “openness” appear, they asked? We are invited to consider several intertwined answers Tranströmer and Kaplinski offered. They include embracing the untamed and stepping away from any decorative use of language – “all rhetoric must be left behind,” Tranströmer, echoing Kaplinski, categorically insisted; evoking the self-cancelling of language itself; or moving altogether beyond language: seeking to transcend it by employing a theme, introducing a practice, or setting up a signpost, all meant to point away from language. And finally, in league with “openness”, “silence” also constitutes a shared recurring theme in Kaplinski’s and Tranströmer’s work, as this article suggests. In order to better explain the importance of “silence”, the article draws attention to American composer John Cage. Informed by the altogether different logic of “openness” Cage employed, for him “silence” became the performance, as it were, and the ambient sounds of the concert hall its music. Acting as a particularly compelling embodiment of “openness” – not unlike the blank page of the poet, the unpublished manuscript of the writer, or the white canvas of the painter – “silence” too united Jaan Kaplinski and Tomas Tranströmer, as servants in their masterful quest for “openness”

Humanitaarteaduste olevik ja tulevik

Vytauto Didžiojo universiteta

Genome stability of bovine in vivo-conceived cleavage-stage embryos is higher compared to in vitro-produced embryos

STUDY QUESTION: Is the rate and nature of chromosome instability (CIN) similar between bovine in vivo-derived and in vitro-cultured cleavage-stage embryos? SUMMARY ANSWER: There is a major difference regarding chromosome stability of in vivo-derived and in vitro-cultured embryos, as CIN is significantly lower in in vivo-derived cleavage-stage embryos compared to in vitro-cultured embryos. WHAT IS KNOWN ALREADY: CIN is common during in vitro embryogenesis and is associated with early embryonic loss in humans, but the stability of in vivo-conceived cleavage-stage embryos remains largely unknown. STUDY DESIGN, SIZE, DURATION: Because human in vivo preimplantation embryos are not accessible, bovine (Bos taurus) embryos were used to study CIN in vivo. Five young, healthy, cycling Holstein Friesian heifers were used to analyze single blastomeres of in vivo embryos, in vitro embryos produced by ovum pick up with ovarian stimulation (OPU-IVF), and in vitro embryos produced from in vitro matured oocytes retrieved without ovarian stimulation (IVM-IVF). PARTICIPANTS/MATERIALS, SETTING, METHODS: Single blastomeres were isolated from embryos, whole-genome amplified and hybridized on Illumina BovineHD BeadChip arrays together with the bulk DNA from the donor cows (mothers) and the bull (father). DNA was also obtained from the parents of the bull and from the parents of the cows (paternal and maternal grandparents, respectively). Subsequently, genome-wide haplotyping and copy-number profiling was applied to investigate the genomic architecture of 171 single bovine blastomeres of 16 in vivo, 13 OPU-IVF and 13 IVM-IVF embryos. MAIN RESULTS AND THE ROLE OF CHANCE: The genomic stability of single blastomeres in both of the in vitro-cultured embryo cohorts was severely compromised (P < 0.0001), and the frequency of whole chromosome or segmental aberrations was higher in embryos produced in vitro than in embryos derived in vivo. Only 18.8% of in vivo-derived embryos contained at least one blastomere with chromosomal anomalies, compared to 69.2% of OPU-IVF embryos (P < 0.01) and 84.6% of IVM-IVF embryos (P < 0.001). LARGE SCALE DATA: Genotyping data obtained in this study has been submitted to NCBI Gene Expression Omnibus (GEO; accession number GSE95358). LIMITATIONS REASONS FOR CAUTION: There were two main limitations of the study. First, animal models may not always reflect the nature of human embryogenesis, although the use of an animal model to investigate CIN was unavoidable in our study. Second, a limited number of embryos were obtained, therefore more studies are warranted to corroborate the findings. WIDER IMPLICATIONS OF THE FINDINGS: Although CIN is also present in in vivo-developed embryos, in vitro procedures exacerbate chromosomal abnormalities during early embryo development. Hence, the present study highlights that IVF treatment compromises embryo viability and should be applied with care. Additionally, our results encourage to refine and improve in vitro culture conditions and assisted reproduction technologies. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Agency for Innovation by Science and Technology (IWT) (TBM-090878 to J.R.V. and T.V.), the Research Foundation Flanders (FWO; G.A093.11 N to T.V. and J.R.V. and G.0392.14 N to A.V.S. and J.R.V.), the European Union's FP7 Marie Curie Industry-Academia Partnerships and Pathways (IAPP, SARM, EU324509 to J.R.V., T.V., O.T, A.D., A.S. and A.K.) and Horizon 2020 innovation programme (WIDENLIFE, 692065 to J.R.V., O.T., T.V., A.K. and A.S.). M.Z.E., J.R.V. and T.V. are co-inventors on a patent application ZL913096-PCT/EP2014/068315-WO/2015/028576 ('Haplotyping and copy-number typing using polymorphic variant allelic frequencies'), licensed to Cartagenia (Agilent Technologies).status: publishe

Guidelines for the design, analysis and interpretation of 'omics' data: focus on human endometrium.

Background'Omics' high-throughput analyses, including genomics, epigenomics, transcriptomics, proteomics and metabolomics, are widely applied in human endometrial studies. Analysis of endometrial transcriptome patterns in physiological and pathophysiological conditions has been to date the most commonly applied 'omics' technique in human endometrium. As the technologies improve, proteomics holds the next big promise for this field. The 'omics' technologies have undoubtedly advanced our knowledge of human endometrium in relation to fertility and different diseases. Nevertheless, the challenges arising from the vast amount of data generated and the broad variation of 'omics' profiling according to different environments and stimuli make it difficult to assess the validity, reproducibility and interpretation of such 'omics' data. With the expansion of 'omics' analyses in the study of the endometrium, there is a growing need to develop guidelines for the design of studies, and the analysis and interpretation of 'omics' data.MethodsSystematic review of the literature in PubMed, and references from relevant articles were investigated up to March 2013.ResultsThe current review aims to provide guidelines for future 'omics' studies on human endometrium, together with a summary of the status and trends, promise and shortcomings in the high-throughput technologies. In addition, the approaches presented here can be adapted to other areas of high-throughput 'omics' studies.ConclusionA highly rigorous approach to future studies, based on the guidelines provided here, is a prerequisite for obtaining data on biological systems which can be shared among researchers worldwide and will ultimately be of clinical benefit