Outer dense ﬁbers stabilize the axoneme to maintain sperm
, Zhengzheng Li
, Ping Ping
, Guishuan Wang
, Xiaobing Yuan
International Peace Maternity & Child Health Hospital, Shanghai Key Laboratory for Reproductive Medicine, School of
Medicine, Shanghai Jiaotong University, Shanghai, China
Department of Assistant Reproduction, International Peace Maternity & Child Health Hospital, Shanghai, China
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, Jiangsu, China
Shanghai Key Laboratory of Brain Functional Genomics (East China Normal University), Ministry of Education, School of Life
Sciences, East China Normal University, Shanghai, China
Hussman Institute for Autism, Baltimore, MD, USA
Received: July 12, 2017; Accepted: October 13, 2017
Outer dense ﬁbers (ODFs), as unique accessory structures in mammalian sperm, are considered to play a role in the protection of the
sperm tail against shear forces. However, the role and relevant mechanisms of ODFs in modulating sperm motility and its pathological
involvement in asthenozoospermia were unknown. Here, we found that the percentage of ODF defects was higher in asthenozoospermic
samples than that in control samples and was signiﬁcantly correlated with the percentage of axoneme defects and non-motile sperm. Fur-
thermore, the expression levels of ODF major components (Odf1, 2, 3, 4) were frequently down-regulated in asthenozoospermic samples.
Intriguingly, the positive relationship between ODF size and sperm motility existed across species. The conditional disruption of Odf2
expression in mice led to reduced sperm motility and the characteristics of asthenozoospermia. Meanwhile, the expression of acetylated
a-tubulin was decreased in sperm from both Odf2 conditional knockout (cKO) mice and asthenozoospermic men. Immunoﬂuorescence
and biochemistry analyses showed that Odf2 could bind to acetylated a-tubulin and protect the acetylation level of a-tubulin in HEK293T
cells in a cold environment. Finally, we found that lithium elevated the expression levels of Odf family proteins and acetylated a-tubulin,
elongated the midpiece length and increased the percentage of rapidly moving sperm in mice. Our results demonstrate that ODFs are
beneﬁcial for sperm motility via stabilization of the axoneme and that hypo-expression of Odf family proteins is involved in the pathogene-
sis of asthenozoospermia. The lithium administration assay will provide valuable insights into the development of new treatments for
outer dense ﬁbers
According to the World Health Organization (WHO) reports, infertility
occurs in approximately 15–20% of couples . About 40–50% of
the infertility cases are caused by male factors. Asthenozoospermia
represents a common disease among human male infertility cases.
The semen from asthenozoospermic patients is characterized by
reduced sperm motility (<40% motile spermatozoa and 32%
progressive spermatozoa) without any signiﬁcant changes in other
The structural integrity of sperm ﬂagella is a prerequisite for
sperm motility. The internal cytoskeletal structure of the ﬂagellum
is called an axoneme, presenting a 9 + 2 formation, which is
constituted by microtubules . It is considered the propulsive
engine of spermatozoa, and its defects are associated with male
infertility [4, 5]. In mammalian sperm, the ﬂagellum presents
complex accessory structures surrounding the central axoneme.
The ODFs are one of these structures. ODFs progress from the
midpiece to the principal piece of the sperm tail, which generates
These authors contributed equally to this work.
*Correspondence to: Fei SUN
ª 2017 The Authors.
Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use,
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J. Cell. Mol. Med. Vol 22, No 3, 2018 pp. 1755-1768