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CFAP61 knockdown aggravates male infertility by inhibiting testosterone secretion by Leydig cells via the MAPK/COX-2 pathway

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Abstract

This study aimed to elucidate the roles of cilia- and flagella-associated protein 61 (CFAP61) in male infertility and its underlying mechanisms. CFAP61 expression levels in the testicular tissues of male patients with infertility were determined using quantitative real-time polymerase chain reaction, immunohistochemical assay, and western blotting. Moreover, the specific roles of CFAP61 in male infertility were evaluated using cell counting kit-8, 5-ethynyl-2'-deoxyuridine, flow cytometry, and enzyme-linked immunosorbent assays. Here, CFAP61 was expressed at low levels in the testicular tissues of male patients with infertility. Functionally, CFAP61 knockdown reduced the Leydig cell viability and testosterone secretion and enhanced apoptosis. A mechanistic study further revealed that silencing CFAP61 promoted the expression levels of mitogen-activated protein kinase (MAPK)/cyclooxygenase-2 (COX-2) signaling pathway-related proteins (p-extracellular signal-regulated kinase (p-ERK), p–c-Jun N-terminal kinase (p-JNK), p-P38, and COX-2). In conclusion, CFAP61 knockdown facilitated male infertility by suppressing Leydig cell viability and testosterone secretion and enhanced cell apoptosis by activating the MAPK/COX-2 pathway. Our data suggest CFAP61 as a potential therapeutic target for male infertility.

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The datasets generated during and analyzed during the current study are available from the corresponding author on reasonable request.

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Contributions

XC conceived and designed the study. WZ performed the experiment and drafted the manuscript. MJ performed the literature searching and data analysis. JQ contributed to the data analysis. XC and WZ discussed the results. XC and WZ revised the manuscript. All authors reviewed the manuscript.

Corresponding author

Correspondence to Xia Chen.

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This study was reviewed and approved by the Ethic Committee of the Medical School of Nantong University (2020173). Informed consent was obtained from the patients involved.

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The authors declare no competing interests.

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Zhu, W., Mao, J., Qin, J. et al. CFAP61 knockdown aggravates male infertility by inhibiting testosterone secretion by Leydig cells via the MAPK/COX-2 pathway. Funct Integr Genomics 23, 340 (2023). https://doi.org/10.1007/s10142-023-01271-1

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  • DOI: https://doi.org/10.1007/s10142-023-01271-1

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