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10.4103/aja202630
A novel homozygous chromosomal deletion encompassing the ACTL9 gene is associated with cIVF polyspermy and male infertility
Xin-Yu Liu1,2,*
Ya Yang3,*
Zi-Li Li4
Min Li5,6
Lei Jin1
Zhou Li1
Shu-Lin Yang1
Li Wu1
Jing Dai7,
Hui He1,
1Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
2Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
3Department of Infection Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
4Genetics and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
5Basic Medical Laboratory, General Hospital of Central Theater Command, Wuhan 430000, China
6Hubei Key Laboratory of Central Nervous System Tumor and Intervention, Wuhan, 43000, China
7NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Xiangya School of Basic Medical Sciences, Central South University, Changsha 410013, China
Correspondence: Dr. H He (hehui_tjh@tjh.tjmu.edu.cn) or Dr. J Dai (daijing2021@csu.edu.cn)
Received: 10 July 2025; Accepted: 12 May 2026; published online: 25 September 2026
| Abstract |
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Actin-like 9 (ACTL9) is a testis-specific actin-like protein located in the perinuclear theca of the sperm head and neck that plays a role in acrosome formation and sperm head shaping. Pathogenic mutations in ACTL9 have been reported to be associated with male infertility and fertilization failure after conventional in vitro fertilization (cIVF) and intracytoplasmic sperm injection (ICSI). In this study, we identified a homozygous chromosomal microdeletion within the ACTL9 gene in an infertile male characterized by polyspermy in cIVF and nearly total fertilization failure in ICSI. Transmission electron microscopy revealed that spermatozoa from the affected individual exhibited a ruffled acrosome, and the inner acrosomal membrane was detached from the nuclear envelope. Immunofluorescence staining revealed the absence of phospholipase C zeta 1 (PLCZ1) protein in mutant spermatozoa, which explains the characteristic multipronuclei observed in cIVF. ICSI and artificial oocyte activation treatment successfully rescued the cIVF polyspermic phenotype and resulted in a live birth. These findings expand the spectrum of ACTL9 mutations and could facilitate the diagnosis of sperm-borne polyspermy.
Keywords: acrosomal detachment; ACTL9 deletion; fertilization failure; male infertility; polyspermy
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