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Biol Reprod. 2016 Sep;95(3):58. doi: 10.1095/biolreprod.116.140996. Epub 2016 Aug 3.

Deficiency of SPATA46, a Novel Nuclear Membrane Protein, Causes Subfertility in Male Mice.

Author information

1
Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, China.
2
Department of Reproductive Medicine, Jinhua People's Hospital, Jinhua, China.
3
Shenzhen Key Laboratory of Genitourinary Cancer, Shenzhen Second People's Hospital, Shenzhen, China tangaifa2004@163.com.
4
Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Clinical College of Anhui Medical University, Shenzhen, China guiyaoting2007@aliyun.com.

Abstract

Teratozoospermia is generally associated with clinical infertility. Despite numerous studies, the molecular mechanisms underlying male infertility are still poorly understood. In the present study, we demonstrated that deletion of Spata46, a gene encoding a novel protein of unknown function found in mouse testis, was responsible for male subfertility, and the cause of subfertility was characterized as abnormal sperm head shape and a failure of sperm-egg fusion. We also demonstrated that SPATA46 was expressed predominantly in condensed spermatids, with a highly specific localization restricted to the subacrosomal area; the protein is located at the nuclear membrane due to a transmembrane region in the N-terminus of the protein. At the subcellular level, SPATA46-deficient condensed spermatids displayed structural defects consisting of a discontinuous nuclear envelope and a cavity in the nucleus associated with an abnormal nuclear shape. Additionally, in vitro, we determined that the absence of SPATA46 led to accumulation of sperm around the perivitelline space of eggs, and the same phenomenon was also observed for natural sperm incubated with an anti-SPATA46 antibody, suggesting functional relevance of SPATA46 for sperm-egg fusion. Taken together, these results indicated that SPATA46 is a novel protein involved in reshaping of the sperm head and sperm-egg fusion.

KEYWORDS:

Spata46; nuclear shaping; sperm-egg fusion; spermiogenesis; subfertility

PMID:
27488028
DOI:
10.1095/biolreprod.116.140996
[Indexed for MEDLINE]

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