Skip to main content
Log in

ADGB variants cause asthenozoospermia and male infertility

  • Original Investigation
  • Published:
Human Genetics Aims and scope Submit manuscript


Asthenozoospermia is one of the main factors leading to male infertility, but the genetic mechanisms have not been fully elucidated. Variants in the androglobin (ADGB) gene were identified in an infertile male characterized by asthenozoospermia. The variants disrupted the binding of ADGB to calmodulin. Adgb–/– male mice were infertile due to reduced sperm concentration (< 1 × 106 /mL) and motility. Spermatogenesis was also abnormal, with malformation of both elongating and elongated spermatids, and there was an approximately twofold increase in apoptotic cells in the cauda epididymis. These exacerbated the decline in sperm motility. It is surprising that ICSI with testicular spermatids allows fertilization and eventually develops into blastocyst. Through mass spectrometry, we identified 42 candidate proteins that are involved in sperm assembly, flagella formation, and sperm motility interacting with ADGB. In particular, CFAP69 and SPEF2 were confirmed to bind to ADGB. Collectively, our study suggests the potential important role of ADGB in human fertility, revealing its relevance to spermatogenesis and infertility. This expands our knowledge of the genetic causes of asthenozoospermia and provides a theoretical basis for using ADGB as an underlying genetic marker for infertile males.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

The data underlying this article are available in the article and in its online supplementary material.


Download references


We are deeply grateful to all the patients and their families for the participation. We would like to thank Mrs. Hong Gao from the electron microscope platform of the School of Basic Medical Sciences of Fudan University and the MS platform of the Institutes of Biomedical Sciences of Fudan University.


This work was sponsored by the National Natural Science Foundation of China (82201767), the Shanghai Sailing Program (21YF1418300), and the SHIPM-pi fund No. JY201801 from Shanghai Institute of Precision Medicine, Ninth People’s Hospital Shanghai Jiao Tong University School of Medicine.

Author information

Authors and Affiliations



ZY and LW collected the samples. RQ performed the experiments. BC and QL analyzed the data. RQ and QS wrote the paper. XS, YK, LW, and QS conceived and designed the experiments. JM, LZ, and WW treated the mice. ZZ, RL, and YZ constructed the plasmids and prepared the electron microscope samples. JD and QL took and processed the images. All authors approved the final manuscript.

Corresponding authors

Correspondence to Qing Sang, Biaobang Chen or Yanping Kuang.

Ethics declarations

Conflict of interest

None of the authors declare any conflict of interest.

Ethical approval

All experiments were approved by the Ethics Committee of the Medical College of Fudan University and the Ninth Hospital affiliated with Shanghai Jiao Tong University. The study was performed conforming to the current Declaration of Helsinki and all individuals provided written informed consent. The animal experimental operation was approved by the ethics committee (2022JS-029).

Consent to participate

All contributors provided written informed consent to participate in this study.

Consent to publish

All contributors provided written informed consent for publication.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 45540 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Qu, R., Zhang, Z., Wu, L. et al. ADGB variants cause asthenozoospermia and male infertility. Hum Genet 142, 735–748 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: