2. Academic Validation
  3. Disruption in ACTL7A causes acrosomal ultrastructural defects in human and mouse sperm as a novel male factor inducing early embryonic arrest

Disruption in ACTL7A causes acrosomal ultrastructural defects in human and mouse sperm as a novel male factor inducing early embryonic arrest

  • Sci Adv. 2020 Aug 28;6(35):eaaz4796. doi: 10.1126/sciadv.aaz4796.
Aijie Xin 1 2,  Ronggui Qu 1,  Guowu Chen 1,  Ling Zhang 1 3 4,  Junling Chen 1,  Chengqiu Tao 3,  Jing Fu 1,  Jianan Tang 2,  Yanfei Ru 2,  Ying Chen 1,  Xiandong Peng 1,  Huijuan Shi 2,  Feng Zhang 1 2 3 4 5,  Xiaoxi Sun 1 4 6
Affiliations

Affiliations

  • 1 Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
  • 2 NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), School of Pharmacy, Fudan University, Shanghai, China.
  • 3 State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
  • 4 Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China.
  • 5 State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
  • 6 Department of Endocrinology and Reproductive Medicine, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
PMID: 32923619 DOI: 10.1126/sciadv.aaz4796
Abstract

Early embryonic arrest is a challenge for in vitro fertilization (IVF). No genetic factors were previously revealed in the sperm-derived arrest of embryonic development. Here, we reported two infertile brothers presenting normal in conventional semen analysis, but both couples had no embryos for transfer after several IVF and intracytoplasmic sperm injection (ICSI). Whole-exome sequencing identified a homozygous missense mutation of ACTL7A in both brothers. This mutation is deleterious and causes sperm acrosomal ultrastructural defects. The Actl7a knock-in mouse model was generated, and male mutated mice showed sperm acrosomal defects, which were completely consistent with the observations in patients. Furthermore, the sperm from ACTL7A/Actl7a-mutated men and mice showed reduced expression and abnormal localization of PLCζ as a potential cause of embryonic arrest and failure of fertilization. Artificial oocyte activation could successfully overcome the Actl7a-mutated sperm-derived infertility, which is meaningful in the future practice of IVF/ICSI for the ACTL7A-associated male infertility.

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