Mouse Round Spermatid Injection

Round spermatids, characterized by their haploid genetic content, represent the precursor cells to mature spermatozoa. Through the innovative technique of ...

First Hospital of Jilin University

Round spermatid injection (ROSI), one of the assistant reproductive technologies, was used to treat partial infertility patients suffering from non-obstructive azoospermia. However, the development efficiency and birth rate of ROSI embryos are extremely low, and it is urgent to investigate the underlying mechanisms of low efficiency to improve the clinical application of ROSI technology. Here, we analyzed and compared the genome stability of the mouse blastocyst and the post-implantation development between ROSI and ICSI embryos. We first sequenced the genome of blastocysts from mouse ROSI embryos that can correctly form male and female pronuclei (2 PN) and found that the genomes of 7 blastocysts were normal. Furthermore, the implantation rate of ROSI 2 PN embryos on embryonic day 7.5 is similar to that of ICSI embryos, and at this time, 37.50% (9/24) of deciduas have no normal gestational sac. The proportion of embryos that survived to embryonic day 11.5 in the ROSI 2 PN group, ROSI non-2 PN group, parthenogenesis group, and ICSI 2 PN group was 51.61%, 7.14%, 0.00%, and 55.00%, respectively. And two smaller fetuses were found in the ROSI 2 PN group, which is not found in the other three groups. In addition, the physiological indexes, including fetus and placenta weight, sex ratio, growth rate, and the natural breeding ability for the offspring obtained from mouse ROSI, were evaluated; ROSI mice exhibited no obvious defect or abnormality and implied that the progeny were safe. Our results provided new evidence to promote the clinical application of ROSI technology.

Evaluation of the post-implantation development of mouse embryos derived from round spermatid injection.

Currently, anti-PD-1/PD-L1 immunotherapy using immune checkpoint inhibitors is widely used in the treatment of multiple cancer types including lung cancer, which is a leading cause of cancer death in the world. However, only a limited proportion of lung cancer patients will benefit from anti-PD-1/PD-L1 therapy. Therefore, it is of importance to predict the response to immunotherapy for the precision treatment of patients. Although the expression of PD-L1 and tumor mutation burden (TMB) are commonly used to predict the clinical response of anti-PD-1/PD-L1 therapy, other factors such as tumor-specific genes, dMMR/MSI, and gut microbiome are also promising predictors for immunotherapy in lung cancer. Furthermore, invasive peripheral blood biomarkers including blood DNA-related biomarkers (e.g., ctDNA and bTMB), blood cell-related biomarkers (e.g., immune cells and TCR), and other blood-related biomarkers (e.g., soluble PD-L1 and cytokines) were utilized to predict the immunotherapeutic response. In this review, the current achievements of anti-PD-1/PD-L1 therapy and the potential biomarkers for the prediction of anti-PD-1/PD-L1 immunotherapy in lung cancer treatment were summarized and discussed.

Research progress of biomarkers in the prediction of anti-PD-1/PD-L1 immunotherapeutic efficiency in lung cancer.

Preclinical trials play critical roles in assessing the safety and efficiency of novel therapeutic strategies for human diseases including live cancer. However, most therapeutic strategies that were proved to be effective in preclinical cancer models failed in human clinical trials due to the lack of appropriate disease animal models. Therefore, it is of importance and urgent to develop a precise animal model for preclinical cancer research. Liver cancer is one of the most frequently diagnosed cancers with low 5-year survival rate. Recently, porcine attracted increasing attentions as animal model in biomedical research. Porcine liver cancer model may provide a promising platform for biomedical research due to their similarities to human being in body size, anatomical characteristics, physiology and pathophysiology. In this review, we comprehensively summarized and discussed the advantages and disadvantages, rationale, current status and progress of pig models for liver cancer research.

Jiarui Wei

Center of Reproductive Medicine,
Center of Prenatal Diagnosis

First Hospital of Jilin University

Mouse Round Spermatid Injection

Jiarui Wei

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First Hospital of Jilin University

Mouse Round Spermatid Injection

Center of Reproductive Medicine,
Center of Prenatal Diagnosis