Atg7 is required for acrosome biogenesis during spermatogenesis in mice.
The acrosome is a specialized organelle that covers the anterior part of the sperm nucleus and plays an essential role in the process of fertilization. The molecular mechanism underlying the biogenesis of this lysosome-related organelle (LRO) is still largely unknown. Here, we show that germ cell-specific Atg7-knockout mice were infertile due to a defect in acrosome biogenesis and displayed a phenotype similar to human globozoospermia; this reproductive defect was successfully rescued by intracytoplasmic sperm injections. Furthermore, the depletion of Atg7 in germ cells did not affect the early stages of development of germ cells, but at later stages of spermatogenesis, the proacrosomal vesicles failed to fuse into a single acrosomal vesicle during the Golgi phase, which finally resulted in irregular or nearly round-headed spermatozoa. Autophagic flux was disrupted in Atg7-depleted germ cells, finally leading to the failure of LC3 conjugation to Golgi apparatus-derived vesicles. In addition, Atg7 partially regulated another globozoospermia-related protein, Golgi-associated PDZ- and coiled-coil motif-containing protein (GOPC), during acrosome biogenesis. Finally, the injection of either autophagy or lysosome inhibitors into testis resulted in a similar phenotype to that of germ cell-specific Atg7-knockout mice. Altogether, our results uncover a new role for Atg7 in the biogenesis of the acrosome, and we provide evidence to support the autolysosome origination hypothesis for the acrosome.
1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
Hongna
H
Wang
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Haifeng
H
Wan
1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
Xixia
X
Li
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Weixiao
W
Liu
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Qi
Q
Chen
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Yaqing
Y
Wang
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Lin
L
Yang
College of Life Sciences, Hebei United University, Tangshan, Hebei 063000, China.
Hongmei
H
Tang
College of Life Sciences, Hebei United University, Tangshan, Hebei 063000, China.
Xiujun
X
Zhang
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Enkui
E
Duan
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Xiaoyang
X
Zhao
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Fei
F
Gao
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Wei
W
Li
D000177:Acrosome / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D000071193:Autophagy-Related Protein 7; D002352:Carrier Proteins / Q000096:biosynthesis; D005854:Germ Cells; D000077614:Golgi Matrix Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology*; D013094:Spermatozoa / Q000002:abnormalities
D048868:Adaptor Proteins, Signal Transducing; C502661:Atg7 protein, mouse; D002352:Carrier Proteins; D000077614:Golgi Matrix Proteins; C435484:Gopc protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D000071193:Autophagy-Related Protein 7