Mitotic Arrest in Teratoma Susceptible Fetal Male Germ Cells

Formation of germ cell derived teratomas occurs in mice of the 129/SvJ strain, but not in C57Bl/6 inbred or CD1 outbred mice. Despite this, there have been few comparative studies aimed at determining the similarities and differences between teratoma susceptible and non-susceptible mouse strains. This study examines the entry of fetal germ cells into the male pathway and mitotic arrest in 129T2/SvJ mice. We find that although the entry of fetal germ cells into mitotic arrest is similar between 129T2/SvJ, C57Bl/6 and CD1 mice, there were significant differences in the size and germ cell content of the testis cords in these strains. In 129T2/SvJ mice germ cell mitotic arrest involves upregulation of p27KIP1, p15INK4B, activation of RB, the expression of male germ cell differentiation markers NANOS2, DNMT3L and MILI and repression of the pluripotency network. The germ-line markers DPPA2 and DPPA4 show reciprocal repression and upregulation, respectively, while FGFR3 is substantially enriched in the nucleus of differentiating male germ cells. Further understanding of fetal male germ cell differentiation promises to provide insight into disorders of the testis and germ cell lineage, such as testis tumour formation and infertility

Understanding Eating Disorders in Elite Gymnastics

Eating disorders and disordered eating are more common in high performance sports than the general population, and particularly so in high performance aesthetic sports. This paper presents some of the conceptual difficulties in understanding and diagnosing eating disorders in high performance gymnasts. It presents qualitative and quantitative data from a study designed to ascertain the pattern of eating disorder symptoms, depressive symptoms and levels of self-esteem amongst national and international level gymnasts from the UK in the gymnastic disciplines of sport acrobatics, tumbling and rhythmic gymnastics

Intrinsic factors and the embryonic environment influence the formation of extragonadal teratomas during gestation

Background: Pluripotent cells are present in early embryos until the levels of the pluripotency regulator Oct4 drop at the beginning of somitogenesis. Elevating Oct4 levels in explanted post-pluripotent cells in vitro restores their pluripotency. Cultured pluripotent cells can participate in normal development when introduced into host embryos up to the end of gastrulation. In contrast, pluripotent cells efficiently seed malignant teratocarcinomas in adult animals. In humans, extragonadal teratomas and teratocarcinomas are most frequently found in the sacrococcygeal region of neonates, suggesting that these tumours originate from cells in the posterior of the embryo that either reactivate or fail to switch off their pluripotent status. However, experimental models for the persistence or reactivation of pluripotency during embryonic development are lacking. Methods: We manually injected embryonic stem cells into conceptuses at E9.5 to test whether the presence of pluripotent cells at this stage correlates with teratocarcinoma formation. We then examined the effects of reactivating embryonic Oct4 expression ubiquitously or in combination with Nanog within the primitive streak (PS)/tail bud (TB) using a transgenic mouse line and embryo chimeras carrying a PS/TB-specific heterologous gene expression cassette respectively. Results: Here, we show that pluripotent cells seed teratomas in post-gastrulation embryos. However, at these stages, induced ubiquitous expression of Oct4 does not lead to restoration of pluripotency (indicated by Nanog expression) and tumour formation in utero, but instead causes a severe phenotype in the extending anteroposterior axis. Use of a more restricted T(Bra) promoter transgenic system enabling inducible ectopic expression of Oct4 and Nanog specifically in the posteriorly-located primitive streak (PS) and tail bud (TB) led to similar axial malformations to those induced by Oct4 alone. These cells underwent induction of pluripotency marker expression in Epiblast Stem Cell (EpiSC) explants derived from somitogenesis-stage embryos, but no teratocarcinoma formation was observed in vivo. Conclusions: Our findings show that although pluripotent cells with teratocarcinogenic potential can be produced in vitro by the overexpression of pluripotency regulators in explanted somitogenesis-stage somatic cells, the in vivo induction of these genes does not yield tumours. This suggests a restrictive regulatory role of the embryonic microenvironment in the induction of pluripotency

Diabetes and Cardiovascular Disease

ii.168 hal.; ill.; 21 c

Report of the European Group for the Study of Insulin Resistance annual meeting, Dublin, 4–6th May 2017

The annual meeting of the European Group for the study of Insulin Resistance (EGIR) was held in Dublin, Ireland in May 2017. Ably organized by Dr. Mesud Hatunic, Consultant Endocrinologist at Mater Misericordiae University Hospital, the conference explored the pathophysiology and treatment of insulin resistance and extended a perspective to include aspects of clinical diabetes care including diabetic retinopathy (Dr. David Keegan, Consultant Vitreo-Retinal Surgeon, Mater University Hospital, Dublin, Ireland), monogenic forms of diabetes (Dr. Maria Byrne, Consultant in Endocrinology and Diabetes, Mater Misericordiae Hospital, Dublin, Ireland) and the impact of gastric bypass surgery (Professor Carel le Roux, Co-Director of the Metabolic Medicine Group, University College, Dublin, Ireland). The group actively welcomed the participation of members who have recently joined from the Pasteur Institute in Lille, France, including Dr. Caroline Bonner, who will co-host the Spring 2018 EGIR meeting there with Professor Francois Pattou. New members are always welcome, e-mail: [email protected] for details