Anatomical Transcriptome Atlas of the Male Mouse Reproductive System During Aging

Yanping Huang; Xiangping Li; Xiangzhou Sun; Jiahui Yao; Fengxin Gao; Zhenqing Wang; Jiaying Hu; Zhu Wang; Bin Ouyang; Xiangan Tu; Xuenong Zou; Wei Liu; Mujun Lu; Chunhua Deng; Qiyun Yang; Yun Xie

doi:10.3389/fcell.2021.782824

Anatomical Transcriptome Atlas of the Male Mouse Reproductive System During Aging

Front Cell Dev Biol. 2022 Feb 8:9:782824. doi: 10.3389/fcell.2021.782824. eCollection 2021.

Authors

Yanping Huang¹, Xiangping Li², Xiangzhou Sun², Jiahui Yao², Fengxin Gao³, Zhenqing Wang², Jiaying Hu⁴, Zhu Wang⁴, Bin Ouyang⁵, Xiangan Tu², Xuenong Zou⁶, Wei Liu¹, Mujun Lu¹, Chunhua Deng², Qiyun Yang², Yun Xie^{2

6}

Affiliations

¹ Department of Urology and Andrology, Renji Hospital, School of Medicine, Shanghai Institute of Andrology, Shanghai Jiao Tong University, Shanghai, China.
² Department of Urology and Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
³ Guangzhou Epibiotek Co., Ltd., Guangzhou, China.
⁴ Department of Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
⁵ Department of Andrology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
⁶ Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Abstract

The elderly males undergo degenerative fertility and testicular endocrine function that jeopardize the reproductive health and well-being. However, the mechanisms underlying reproductive aging are unclear. Here, we tried to address this by investigating the phenotypes and transcriptomes of seven regions of the male mouse reproductive tract: the testis, efferent ductules, initial segment, caput, corpus and cauda epididymidis, and vas deferens, in adult (3 months) and aged (21 months) mice. Quantitative PCR, immunohistochemistry, immunofluorescent staining, and enzyme-linked immunosorbent assay were performed for the analysis of gene expression in mice, human tissues, and semen samples. Aged male mice showed both systematic and reproductive changes, and remarkable histological changes were detected in the testis and proximal epididymis. Transcriptomes of the male reproductive tract were mapped, and a series of region-specific genes were identified and validated in mouse and/or human tissues, including Protamine 1 (Prm2), ADAM metallopeptidase domain 28 (Adam28), Ribonuclease A family member 13 (Rnase13), WAP four-disulfide core domain 13 (Wfdc13), and Wfdc9. Meanwhile, age-related transcriptome changes of different regions of the male reproductive tract were characterized. Notably, increased immune response was functionally related to the male reproductive aging, especially the T cell activation. An immune response-associated factor, phospholipase A2 group IID (Pla2g2d), was identified as a potential biomarker for reproductive aging in mice. And the PLA2G2D level in human seminal plasma surged at approximately 35 years of age. Furthermore, we highlighted Protein tyrosine phosphatase receptor type C (Ptprc), Lymphocyte protein tyrosine kinase (Lck), Microtubule associated protein tau (Mapt), and Interferon induced protein with tetratricopeptide repeats 3 (Ifit3) as critical molecules in the aging of initial segment, caput, caput, and cauda epididymidis, respectively. This study provides an RNA-seq resource for the male reproductive system during aging in mice, and is expected to improve our understanding of male reproductive aging and infertility.

Keywords: PLA2G2D; epididymis; male reproductive system; reproductive aging; testis; transcriptome.