LncRNA8276 Primes Cell-Cell Adhesion for Regulation of Spermatogenesis

Human sperm concentration and motility have dropped dramatically (50%) in the past few decades, and environmental factors are involved in this decline. Long non-coding RNAs (lncRNA) have been discovered to be involved in many cellular processes such as spermatogenesis. This investigation aimed to explore the role of lncRNA8276 in mice spermatogenesis.

The expression of lncRNA8276 was modified by knockdown or overexpression in mouse testes or spermatogonial stem cells (C18-4 cell line). The sperm quality was determined in F0 and F1 generational mice. And the underlying mechanisms were studied with the gene expression and/or protein expression of spermatogenesis related genes and cell junction related genes by different methods.

In current investigation, we discovered that the sperm lncRNA8276 was decreased by NH₃/H₂S in three generations (F0, F1, and F2) mouse sperm. In vivo testicular knockdown lncRNA8276 led to the decline in the sperm concentration and motility in both F0 generation (muF0) and F1 generation (muF1) via the impairment in cell junctions which control the dynamic remodeling and the permeability of blood-testis barrier to ensure the successful spermatogenesis. The data were further confirmed in mouse spermatogonia stem cell line C18-4 cells through knockdown lncRNA8276. Our study proves that lncRNA8276 is involved in spermatogenesis through the regulating cell-cell junctions which may be a target for the improving spermatogenesis and male fertility, or male contraception.

This investigation offers a potential therapeutic strategy for male infertility.

Note:
Funding Information: This study was supported by the National Natural Science Foundation of China (31772408 and 32070536 to YZ; 31672428 to HZ). We thank the investigators and staff of The Beijing Genomics Institute (BGI) for technical support.

Declaration of Interests: The authors declare no competing interests.

Ethics Approval Statement: All animal procedures used in this study were approved by the Animal Care and Use Committee of the Institute of Animal Sciences of Chinese Academy of Agricultural Sciences (IAS2018-1007).

Keywords: LncRNA8276, Spermatogenesis, Semen quality, Male fertility, Cell-cell junction

Suggested Citation: Suggested Citation

Xiong, Bohui and Jiang, Yue and Wang, Yandi and Han, Xiao and Zhang, Cong and Zhong, Ruqing and Ge, Wei and Han, Baoquan and Ge, Zhaojia and Huang, Gui’an and Yin, Shen and Shen, Wei and Sun, Qingyuang and Sun, Zhongyi and Zhang, Hongfu and Zhao, Yong, LncRNA8276 Primes Cell-Cell Adhesion for Regulation of Spermatogenesis. Available at SSRN: https://ssrn.com/abstract=4029296 or http://dx.doi.org/10.2139/ssrn.4029296