Novel biallelic HFM1 variants cause severe oligozoospermia with favorable intracytoplasmic sperm injection outcome.

Liu LIU; Yi-Ling ZHOU; Wei-Dong TIAN; Feng JIANG; Jia-Xiong WANG; Feng ZHANG; Chun-Yu LIU; Hong ZHU

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Novel biallelic HFM1 variants cause severe oligozoospermia with favorable intracytoplasmic sperm injection outcome.

Author: Liu LIU ¹ ; Yi-Ling ZHOU ¹ ; Wei-Dong TIAN ² ; Feng JIANG ¹ ; Jia-Xiong WANG ³ ; Feng ZHANG ⁴ ; Chun-Yu LIU ⁴ ; Hong ZHU ¹
Author Information

1. Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
2. Department of Computational Biology, School of Life Sciences, Fudan University, Shanghai 200438, China.
3. Center for Reproduction and Genetics, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou 215002, China.
4. Soong Ching Ling Institute of Maternity and Child Health, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
Publication Type:Case Reports
Keywords: ICSI; male infertility; oligozoospermia
MeSH: Humans; Male; Sperm Injections, Intracytoplasmic; Oligospermia/therapy*; Adult; Spermatozoa/ultrastructure*; Exome Sequencing; Mutation
From: Asian Journal of Andrology 2025;27(6):751-756
CountryChina
Language:English
Abstract: Male factors contribute to 50% of infertility cases, with 20%-30% of cases being solely attributed to male infertility. Helicase for meiosis 1 ( HFM1 ) plays a crucial role in ensuring proper crossover formation and synapsis of homologous chromosomes during meiosis, an essential process in gametogenesis. HFM1 gene mutations are associated with male infertility, particularly in cases of non-obstructive azoospermia and severe oligozoospermia. However, the effects of intracytoplasmic sperm injection (ICSI) in HFM1 -related infertility cases remain inadequately explored. This study identified novel biallelic HFM1 variants through whole-exome sequencing (WES) in a Chinese patient with severe oligozoospermia, which was confirmed by Sanger sequencing. The pathogenicity of these variants was assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunoblotting, which revealed a significant reduction in HFM1 mRNA and protein levels in spermatozoa compared to those in a healthy control. Transmission electron microscopy revealed morphological abnormalities in sperm cells, including defects in the head and flagellum. Despite these abnormalities, ICSI treatment resulted in a favorable fertility outcome for the patient, indicating that assisted reproductive techniques (ART) can be effective in managing HFM1 -related male infertility. These findings offer valuable insights into the management of such cases.