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Pancreatic lipase-related protein 2 is selectively expressed by peritubular myoid cells in the murine testis and sustains long-term spermatogenesis

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Abstract

Spermatogenesis is a complicated process of germ cell differentiation that occurs within the seminiferous tubule in the testis. Peritubular myoid cells (PTMCs) produce major components of the basement membrane that separates and ensures the structural integrity of seminiferous tubules. These cells secrete niche factors to promote spermatogonial stem cell (SSC) maintenance and mediate androgen signals to direct spermatid development. However, the regulatory mechanisms underlying the identity and function of PTMCs have not been fully elucidated. In the present study, we showed that the expression of pancreatic lipase-related protein 2 (Pnliprp2) was restricted in PTMCs in the testis and that its genetic ablation caused age-dependent defects in spermatogenesis. The fertility of Pnliprp2 knockout animals (Pnliprp2−/−) was normal at a young age but declined sharply beginning at 9 months. Pnliprp2 deletion impaired the homeostasis of undifferentiated spermatogonia and severely disrupted the development and function of spermatids. Integrated analyses of single-cell RNA-seq and metabolomics data revealed that glyceride metabolism was changed in PTMCs from Pnliprp2−/− mice. Further analysis found that 60 metabolites were altered in the sperm of the Pnliprp2−/− animals; notably, lipid metabolism was significantly dysregulated. Collectively, these results revealed that Pnliprp2 was exclusively expressed in PTMCs in the testis and played a novel role in supporting continual spermatogenesis in mice. The outcomes of these findings highlight the function of lipid metabolism in reproduction and provide new insights into the regulation of PTMCs in mammals.

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Data availability

These authors declare that the data supporting the findings of this study are available within the paper and its supplementary materials or are available from the corresponding author upon reasonable request. Single-cell RNA-seq datasets have been uploaded to NCBI (BioProject: PRJNA898878).

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Acknowledgements

The authors would like to thank the members of Reproductive Biology and Functional Genomics at the Northwest Institute of Plateau Biology for inspiring discussions and suggestions. We are also grateful for all financial support.

Funding

This work was supported by the National Natural Science Foundation of China (Grants No. 31771656 and 31571539) and Natural Science Foundation of Qinghai Province (2020-ZJ-902). G.X.J. was supported by the Youth Innovation Promotion Association of Chinese Academy of Sciences (2021432) and Qinghai Kunlun Talents Program.

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Author notes

  1. Hai-Ping Tao, Teng-Fei Lu and Shuang Li have contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810008, Qinghai, China

    Hai-Ping Tao, Shuang Li, Gong-Xue Jia, Xiao-Na Zhang & Qi-En Yang

  2. University of Chinese Academy of Sciences, Beijing, 100049, China

    Hai-Ping Tao, Shuang Li, Gong-Xue Jia, Xiao-Na Zhang & Qi-En Yang

  3. Qinghai Key Laboratory of Animal Ecological Genomics, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810001, Qinghai, China

    Hai-Ping Tao, Shuang Li, Gong-Xue Jia, Xiao-Na Zhang & Qi-En Yang

  4. State Key Laboratory of Farm Animal Biotechnology Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China

    Teng-Fei Lu & Yun-Peng Hou

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Contributions

QY and YH conceived and designed the study. HT and TL performed most of the experiments. XZ conducted all the mass lipid metabolomic data analyses. SL and HT conducted the scRNA-seq data analyses. HT and GJ analyzed the data. HT and QY wrote the manuscript. All authors read and approved the final paper.

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Correspondence to Qi-En Yang or Yun-Peng Hou.

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Animal experiments were performed in accordance with the Guide for the Care and Use of Laboratory Animals and were approved by the Animal Welfare and Ethics Committee at the Northwest Institute of Plateau Biology, Chinese Academy of Sciences (approval code: hwipb012).

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Tao, HP., Lu, TF., Li, S. et al. Pancreatic lipase-related protein 2 is selectively expressed by peritubular myoid cells in the murine testis and sustains long-term spermatogenesis. Cell. Mol. Life Sci. 80, 217 (2023). https://doi.org/10.1007/s00018-023-04872-y

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