Effect of microgravity on mammalian embryo development evaluated at the International Space Station.

Mammalian embryos differentiate into the inner cell mass (ICM) and trophectoderm at the 8-16 cell stage. The ICM forms a single cluster that develops into a single fetus. However, the factors that determine differentiation and single cluster formation are unknown. Here we investigated whether embryos could develop normally without gravity. As the embryos cannot be handled by an untrained astronaut, a new device was developed for this purpose. Using this device, two-cell frozen mouse embryos launched to the International Space Station were thawed and cultured by the astronauts under microgravity for 4 days. The embryos cultured under microgravity conditions developed into blastocysts with normal cell numbers, ICM, trophectoderm, and gene expression profiles similar to those cultured under artificial-1 g control on the International Space Station and ground-1 g control, which clearly demonstrated that gravity had no significant effect on the blastocyst formation and initial differentiation of mammalian embryos.

Paternally inherited H3K27me3 affects chromatin accessibility in mouse embryos produced by round spermatid injection.

Round spermatid injection (ROSI) results in a lower birth rate than intracytoplasmic sperm injection, which has hampered its clinical application. Inefficient development of ROSI embryos has been attributed to epigenetic abnormalities. However, the chromatin-based mechanism that underpins the low birth rate in ROSI remains to be determined. Here, we show that a repressive histone mark, H3K27me3, persists from mouse round spermatids into zygotes in ROSI and that round spermatid-derived H3K27me3 is associated with less accessible chromatin and impaired gene expression in ROSI embryos. These loci are initially marked by H3K27me3 but undergo histone modification remodelling in spermiogenesis, resulting in reduced H3K27me3 in normal spermatozoa. Therefore, the absence of epigenetic remodelling, presumably mediated by histone turnover during spermiogenesis, leads to dysregulation of chromatin accessibility and transcription in ROSI embryos. Thus, our results unveil a molecular logic, in which chromatin states in round spermatids impinge on chromatin accessibility and transcription in ROSI embryos, highlighting the importance of epigenetic remodelling during spermiogenesis in successful reproduction.

Mailing viable mouse freeze-dried spermatozoa on postcards.

Freeze-drying techniques allow the preservation of mammalian spermatozoa without using liquid nitrogen. However, the current method requires the use of glass ampoules, which are breakable, expensive, and bulky to store or transport. In this study, we evaluated whether mouse freeze-dried (FD) spermatozoa can be preserved and transported on thin materials. In this study, we demonstrated that FD sperm can be preserved in thin plastic sheets. Its DNA integrity was comparable to that of glass ampoule spermatozoa, and healthy offspring were obtained after preservation at -30°C for more than 3 months. We attached preserved FD sperm to postcards, and transported these to other laboratory inexpensively at room temperatures without any protection. This method will facilitate the preservation of thousands of mouse strains in a single card holder, promote collaboration between laboratories, conservation of genetic resources, and assisted reproductive technology.

Evaluating the long-term effect of space radiation on the reproductive normality of mammalian sperm preserved on the International Space Station.

Space radiation may cause DNA damage to cells and concern for the inheritance of mutations in offspring after deep space exploration. However, there is no way to study the long-term effects of space radiation using biological materials. Here, we developed a method to evaluate the biological effect of space radiation and examined the reproductive potential of mouse freeze-dried spermatozoa stored on the International Space Station (ISS) for the longest period in biological research. The space radiation did not affect sperm DNA or fertility after preservation on ISS, and many genetically normal offspring were obtained without reducing the success rate compared to the ground-preserved control. The results of ground x-ray experiments showed that sperm can be stored for more than 200 years in space. These results suggest that the effect of deep space radiation on mammalian reproduction can be evaluated using spermatozoa, even without being monitored by astronauts in Gateway.

Effectiveness of group cognitive-behavioral therapy in reducing self-stigma in Japanese psychiatric patients.

OBJECTIVE: There is evidence that the stigma surrounding mental illness may be greater in Japan than elsewhere. However, few Japanese studies have focused on self-stigma (the internalization of social stigma), and few interventions to reduce self-stigma exist. To remedy this deficiency, we evaluated the efficacy of group cognitive-behavioral therapy (CBT) in reducing self-stigma and examined the relationship between cognitive restructuring and self-stigma. METHODS: We administered a 10-session group CBT program to 46 Japanese outpatients with anxiety and depressive symptoms (36 men, 10 women; mean age=38.57 years, SD=8.33; 20 diagnosed with mood disorders; 24 with neurotic, stress-related, or somatoform disorders; and 2 with other disorders). A pretest-posttest design was used to examine the relationship between cognitive restructuring and self-stigma. Outcomes were measured using the Japanese versions of the Devaluation-Discrimination Scale, Dysfunctional Attitude Scale, Beck Depression Inventory-II, State-Trait Anxiety Inventory State-Form, and Rosenberg's Self Esteem Scale. RESULTS: Participants exhibited significant improvements in depression, anxiety, and maladjusted cognitive bias and reductions in self-stigma. Cognitive bias was significantly correlated with self-stigma. CONCLUSIONS: Group CBT is effective in improving both emotional symptoms and self-stigma in outpatients with anxiety and depressive symptoms. Reduction in self-stigma plays a mediating role in alleviating emotional symptoms and improving cognition.