• PMID: 30680919
• Gene Name: TPPP2
• Condition: Oligoasthenozoospermia
• Association: Associated
• Sex: Male
• Infertility type: Male infertility

Deficiency of TPPP2, a factor linked to oligoasthenozoospermia, causes subfertility in male mice

Zhu F, Yan P, Zhang J, Cui Y, Zheng M, Cheng Y, Guo Y, Yang X, Guo X, Zhu H.

Oligoasthenozoospermia is a major cause of male infertility; however, its etiology and pathogenesis are unclear and may be associated with specific gene abnormalities. This study focused on Tppp2 (tubulin polymerization promoting protein family member 2), whose encoded protein localizes in elongating spermatids at stages IV-VIII of the seminiferous epithelial cycle in testis and in mature sperm in the epididymis. In human and mouse sperm, in vitro inhibition of TPPP2 caused significantly decreased motility and ATP content. Studies on Tppp2 knockout (KO) mice demonstrated that deletion of TPPP2 resulted in male subfertility with a significantly decreased sperm count and motility. In Tppp2(-/-) mice, increased irregular mitochondria lacking lamellar cristae, abnormal expression of electron transfer chain molecules, lower ATP levels, decreased mitochondrial membrane potential and increased apoptotic index were observed in sperm, which could be the potential causes for its oligoasthenozoospermia phenotype. Moreover, we identified a potential TPPP2-interactive protein, eEf1b (eukaryotic translation elongation factor 1 beta), which plays an important role in protein translation extension. Thus, TPPP2 is probably a potential pathogenic factor in oligoasthenozoospermia. Deficiency of TPPP2 might affect the translation of specific proteins, altering the structure and function of sperm mitochondria, and resulting in decreased sperm count, motility and fertility. CI - © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. FAU - Zhu, Feng AU - Zhu F AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China. FAU - Yan, Peipei AU - Yan P AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China. AD - Department of Pathology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital Nanjing, China. FAU - Zhang, Jingjing AU - Zhang J AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China. FAU - Cui, Yiqiang AU - Cui Y AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China. FAU - Zheng, Meimei AU - Zheng M AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China. FAU - Cheng, Yiwei AU - Cheng Y AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China. FAU - Guo, Yueshuai AU - Guo Y AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China. FAU - Yang, Xiaoyu AU - Yang X AD - Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Guo, Xuejiang AU - Guo X AD - State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China.