Dissecting potential mechanisms of lactate-dependent Sertoli cell proliferation and gene expression

ZHANG Xiaona; JIA Gongxue; WU Shixin; WAN Ruidong; WANG Yujun; YANG Qien

doi:10.16829/j.slxb.150778

ACTA THERIOLOGICA SINICA >

2023 , Vol. 43 >Issue 5: 568 - 579

DOI: https://doi.org/10.16829/j.slxb.150778

ORIGINAL PAPERS

Dissecting potential mechanisms of lactate-dependent Sertoli cell proliferation and gene expression

ZHANG Xiaona ,
JIA Gongxue ,
WU Shixin ,
WAN Ruidong ,
WANG Yujun ,
YANG Qien

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1 Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810001, China;
2 University of Chinese Academy of Sciences, Beijing 100049, China;
3 Qinghai Key Laboratory of Animal Ecological Genomics, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810001, China

Received date: 2023-02-14

Revised date: 2023-07-20

Online published: 2023-09-22

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Abstract

Sertoli cells proliferate in fetal and neonatal testes and remain quiescent in adult life. Functional evidence suggests that the size of the Sertoli cell population determines sperm production and fertility. However, the factors that regulate Sertoli cell proliferation and maturation are not fully understood. Lactate, which is secreted by Sertoli cells via lactate dehydrogenase, plays a critical role in cell fate determination. We found that Ldha mRNA is present in mouse testes and immunohistochemical staining confirmed that LDHA is enriched in Sertoli cells. To study the function of LDHA in Sertoli cells, we prepared a conditional knockout mouse model using Amh-Cre and Ldha^fl/fl mice. The results showed that LDHA deficiency resulted in a significant reduction in the number of Sertoli cells, which was (18. 27 ±0. 60) /cell in Ldha-cKO mice compared to (21. 1 ±0. 68) /cell in control mice. Further analysis revealed that the proliferative capacity of Sertoli cells in Ldha-cKO mice decreased by 17. 0% and 9. 0% at Embryonic day 16. 5 and Day 0, respectively, while cell apoptosis increased by 86. 9% and 459. 0%, respectively. After incubation with 10 mmol/L lactic acid for 24 h, 936 significantly differentially expressed genes were identified in Sertoli cells of the knockout mouse, of which 695 were upregulated and 241 were downregulated. GO and KEGG enrichment analyses revealed that the MAPK pathway and PI3K-AKT signaling pathway were upregulated, while DNA replication and oxidative phosphorylation were downregulated. Hence, it can be concluded that LDHA is expressed in mouse Sertoli cells and plays an important role in regulating Sertoli cell proliferation.

Key words： Lactate; Sertoli cells; Proliferation; Apoptosis

Cite this article

ZHANG Xiaona , JIA Gongxue , WU Shixin , WAN Ruidong , WANG Yujun , YANG Qien . Dissecting potential mechanisms of lactate-dependent Sertoli cell proliferation and gene expression[J]. ACTA THERIOLOGICA SINICA, 2023 , 43(5) : 568 -579 . DOI: 10.16829/j.slxb.150778

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