Recently, Lab Animal, an international academic journal under Nature, published a research paper entitled “Oxidation Reduction Steady State Construction of Male Reproductive Dysfunction Based on LanCL1-Regulated Spermatogenesis Process” jointly published online by the Laboratory of Laboratory Animal Disease Model Research Of Sichuan Agricultural University, Southern University of Science and Technology, West China Hospital of Sichuan University and other units. Based on the antioxidant gene LanCL1, a series of experimental animal models for the study of male reproductive dysfunction were established by means of gene knockout and transgeneation, and the mechanism of action of LanCL1 protein in response to and regulation of sperm cell redilox balance and testicular homeostasis during spermatogenesis was revealed for the first time.
The research results were published in the form of a cover paper courtesy of Sichuan Agricultural University
According to the World Health Organization, infertility will become the third largest disease in the 21st century after tumors and cardiovascular and cerebrovascular diseases. The proportion of infertility in European and American countries has exceeded 15% of the total number of couples, and the male factor accounts for 50%. Oxidative stress is considered to be an important factor in male reproductive dysfunction, and about 50%-80% of male infertility patients have found oxidative damage caused by reactive oxygen species (ROS). Therefore, it is a good theoretical basis and considerable prospective to study the regulatory mechanism of redox balance during spermatogenesis and establish a suitable animal disease model based on this.
Most of the identified cellular redox balance regulatory mechanisms do not affect male fertility after the loss of male germ cells, suggesting that more important mechanisms have yet to be revealed. On the basis of the previous work, the research team of our university used the means of gene knockout and transgenic gene to establish systemic knockout, germ cell specific knockout and germ cell specific transgenic mice of LanCL1 based on the antioxidant gene LanCL1. It was found that LanCL1 is a male germ cell-specific marker whose deletion disrupts the redox balance during sperm cell development, which in turn affects the homeostasis of spermatogenesis, including the proliferation and differentiation of spermatogonial stem cells, sperm survival, and male fertility abnormalities. LanCL1, on the other hand, can resist sperm cell oxidative damage caused by obesity and male fertility decline after sperm cell specific overexpression. In addition, the study demonstrated that the important transcriptional regulator SP1 is involved in the regulatory mechanism of LanCL1 response to the redox balance of sperm cells during spermatogenesis. The above studies reveal the important biological function of the SP1-LanCL1 axis in the male reproductive system, as well as the wide application prospect of LanCL1-based genetically modified mice in the study of male reproductive dysfunction.
Sichuan Agricultural University is the first completion unit, and professors Huang Chao and Chen Zhengli of the College of Veterinary Medicine are the first authors and corresponding authors of the paper, respectively; Yang Chengcheng, a master’s student in 2021, and Dr. Pang Dejiang of Sichuan University are the co-first authors, Xiao Bo, professor of Southern University of Science and Technology, and Chen Mina, associate researcher of Sichuan University, are the co-corresponding authors of the paper.
The research was funded by the National Natural Science Foundation of China, the National Science and Technology Support Program and the Discipline Construction Dual Branch Program of Sichuan Agricultural University. (Source: China Science Daily Zhang Qingdan)
Related paper information:https://doi.org/10.1038/s41684-022-00961-w