From the farm to the lab: how chicken embryos contribute to the field of teratology

Funding This study received no specific grant from any funding agency in the public, commercial or not-for402 profit sectors. Acknowlegment We would like to thank all previous researches that established chicken embryos as a really important and respected experimental model to the teratology field through the history. NV lab funded by Royal Society, Wellcome Trust, Sarcoma UK, NIH. LRF lab funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [grant number 424362/2018-0], Fundo de Incentivo a Pesquisa e Eventos (FIPE) of the Hospital de Clínicas de Porto Alegre (HCPA) [grant numbers 2019-0649 and 2017-0342] and PROPESQ/UFRGS through “Recently Hired Professors” [Call 001/2019]. The authors would like to Sophia Martins Simon de Matos for technical assistance on Figure 1 drawing.Peer reviewedPublisher PD

From the farm to the lab : how chicken embryos contribute to the field of teratology

Congenital anomalies and its causes, particularly, by external factors are the aim of the field called teratology. The external factors studied by teratology are known as teratogens and can be biological or environmental factors for example, chemicals, medications, recreational drugs, environmental pollutants, physical agents (e.g., X-rays and maternal hyperthermia) and maternal metabolic conditions. Proving the teratogenicity of a factor is a difficult task requiring epidemiology studies as well as experimental teratology evidence from the use of animal models, one of which is the chicken embryo. This model in particular has the advantage of being able to follow development live and in vivo, with rapid development hatching around 21 days, is cheap and easy to manipulate and to observe development. All this allows the chicken embryo to be used in drug screening studies, teratogenic evaluation and studies of mechanisms of teratogenicity. The chicken embryo shares morphological, biochemical and genetic similarities with humans as well as mammalian species, making them ideal to ascertain the actions of teratogens, as well as screen drugs to test for their safety. Pre-clinical trials for new drugs are carried out in rodents and rabbits, however, chicken embryos have been used to screen new compounds or analogs of thalidomide as well as to investigate how some drugs can lead to congenital malformations. Indeed, the chicken embryo has proved valuable in understanding how many congenital anomalies, seen in humans, arise following teratogen exposure. The aim of this review is to highlight the role of the chicken embryo as an experimental model for studies in teratology, exploring its use in drug screening studies, phenotypic evaluation and studies of teratogenic mechanisms of action. Here, we discuss many known teratogens, that have been evaluated using the chicken embryo model including some medicines, such as, thalidomide, valproic acid; recreational drugs including alcohol; environmental influences, such as viruses, specifically ZIKV, which is a newly discovered human teratogen. In addition, we discuss how the chicken embryo has provided insight on the mechanisms of teratogenesis of many compounds and also how this impact on drug safety

Vertebrate embryos as tools for anti-angiogenic drug screening and function

Shaunna Beedie is a recipient of a Wellcome Trust-NIH PhD Studentship (Grant number 098252/Z/12/Z). Alexandra J. Diamond is a recipient of a BBSRC EastBIO DTP PhD Scholarship. Lucas Rosa Fraga is a recepient of a PhD scholarship from the Science Without Borders program – CNPq Brazil – INAGEMP/ Grant CNPq 573993/2008-4 Shaunna Beedie and William D. Figg are supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U.S. Government.Peer reviewedPostprin

Expression profiles of meiotic genes in male vs. female gonads and gametes : insights into fertility issues

Gametes are specialized cells that, at fertilization, give rise to a totipotent zygote capable of generating an entire organism. Female and male germ cells undergo meiosis to produce mature gametes; however, sex-specific events of oogenesis and spermatogenesis contribute to specific roles of gametes in reproductive issues. We investigate the differential gene expression (DGE) of meiosis-related genes in human female and male gonads and gametes in normal and pathological conditions. The transcriptome data for the DGE analysis was obtained through the Gene Expression Omnibus repository, comprising human ovary and testicle samples of the prenatal period and adulthood, additionally to male (nonobstructive azoospermia (NOA) and teratozoospermia), and female (polycystic ovary syndrome (PCOS) and advanced maternal age) reproductive conditions. Gene ontology terms related to meiosis were associated with 678 genes, of which 17 genes in common were differentially expressed between the testicle and ovary during the prenatal period and adulthood. Except for SERPINA5 and SOX9, the 17 meiosis-related genes were downregulated in the testicle during the prenatal period and upregulated in adulthood compared to the ovary. No differences were observed in the oocytes of PCOS patients; however, meiosis-related genes were differentially expressed according to the patient’s age and maturity of the oocyte. In NOA and teratozoospermia, 145 meiosis-related genes were differentially expressed in comparison to the control, including OOEP; despite no recognized role in male reproduction, OOEP was co-expressed with genes related to male fertility. Taking together, these results shed light on potential genes that might be relevant to comprehend human fertility disorders

The Primodos components Noretheristerone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafish embryos

Acknowledgements The authors thank Amanda Berg, Zoe Finlayson, Lisa Salhi and Elizabeth Stewart, for help with preliminary studies; Alexandra J. Rafipay (nee Diamond) and Jonathan Smith for lab assistance and discussions and Jesse Olszynko-Gryn, Tobias Arndt, Marie Lyon for discussions on Primodos. Lucas Rosa Fraga was funded by a PhD scholarship from the Science without Borders program – CNPq Brazil – INAGEMP/ Grant CNPq 573993/2008-4 and Samantha Brown was funded by a PhD scholarship from the University of Aberdeen.Peer reviewedPublisher PD

Molecular mechanisms of Zika virus teratogenesis from animal studies : a systematic review protocol

Background: Due to the diversity of studies in animal models reporting that molecular mechanisms are involved in the teratogenic effect of the Zika virus (ZIKV), the objective of the present study is to evaluate the methodological quality of these studies, as well as to demonstrate which genes and which molecular pathways are affected by ZIKV in different animal models. Methods: This search will be performed in four databases: PubMed/MEDLINE, EMBASE, Web of Science, and Scopus, as well as in the grey literature. The studies selection process will be reported through the PRISMA Statement diagram model. All studies describing the molecular mechanisms possibly involved in the development of malformations caused by embryonic/fetal ZIKV exposure in animal models with an appropriate control group and methodology will be included (including, for instance, randomized and non-randomized studies). All animals used as experimental models for ZIKV teratogenesis may be included as long as exposure to the virus occurred during the embryonic/fetal period. From the selected studies, data will be extracted using a previously prepared standard form. Bias risk evaluation will be conducted following the SYRCLE’s Risk of Bias tool. All data obtained will be tabulated and organized by outcomes (morphological and molecular). Discussion: With the proposed systematic review, we expect to present results about the methodological quality of the published studies with animal models that investigated the molecular mechanisms involved in the teratogenic effect of ZIKV, as well as to show the studies with greater reliability

COVID-19 during pregnancy and adverse outcomes : concerns and recommendations from The Brazilian Teratology Information Service

SARS-CoV-2 virus was first identified in the beginning of 2020 and has spread all over the world, causing the Coronavirus Disease 2019 (COVID-19) pandemic. The virus is a member of the Coronavirus family, which includes viruses that cause common cold, Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). MERS and SARS are known by causing adverse events in pregnancy. Considering that SARS-CoV-2 is a new infection agent, little is known about the risk of its infection to human embryo/fetal development. However, SARS and MERS were associated with negative outcomes, such as miscarriage, preterm birth, intrauterine growth restriction and perinatal death. Here, we raise concerns and possibilities related the harmful potential of SARS-CoV-2 and COVID-19 to pregnancy, discussing symptoms, immunological changes during pregnancy, SARS-CoV-2 mutation rate (and the risks related to it). Finally, we point out recommendations to be performed by the scientific community and health care workers in order to identify and to manage potential risks to pregnant women and their babies