LRGUK-1 is required for basal body and manchette function during spermatogenesis and male fertility.

Yan Liu,Christopher J Ormandy,Duangporn Jamsai,Athina Efthymiadis,Hidenobu Okuda,D Jo Merriner,David M De Kretser,David A Jans,Belinda Whittle,Chris C Goodnow,Liza O’Donnell,Robert I Mclachlan,Anne E O’Connor,Moira K O’Bryan,Kathleen Deboer

doi:10.1371/journal.pgen.1005090

Abstract

Male infertility affects at least 5% of reproductive age males. The most common pathology is a complex presentation of decreased sperm output and abnormal sperm shape and motility referred to as oligoasthenoteratospermia (OAT). For the majority of OAT men a precise diagnosis cannot be provided. Here we demonstrate that leucine-rich repeats and guanylate kinase-domain containing isoform 1 (LRGUK-1) is required for multiple aspects of sperm assembly, including acrosome attachment, sperm head shaping and the initiation of the axoneme growth to form the core of the sperm tail. Specifically, LRGUK-1 is required for basal body attachment to the plasma membrane, the appropriate formation of the sub-distal appendages, the extension of axoneme microtubules and for microtubule movement and organisation within the manchette. Manchette dysfunction leads to abnormal sperm head shaping. Several of these functions may be achieved in association with the LRGUK-1 binding partner HOOK2. Collectively, these data establish LRGUK-1 as a major determinant of microtubule structure within the male germ line.

Highlights

Male infertility affects at least 5% men of reproductive age in the western societies [1]
The most common clinical presentation for male infertility is a complex mixture of abnormal sperm output, shape and motility referred to as oligoasthenoteratozoospermia (OAT)
In an effort to define an origin of OAT we have analysed a mouse model of leucine-rich repeats and guanylate kinase-domain containing isoform 1 (LRGUK-1) dysfunction

Summary

Introduction

Male infertility affects at least 5% men of reproductive age in the western societies [1]. The morphological and motility aspects of OAT likely have their origins in spermiogenesis, the process wherein round haploid germ cells are transformed into highly polarized sperm with the potential for motility and fertility. This process takes approximately two weeks in the mouse and involves several thousand different gene products [4]. Three of the major aspects of spermiogenesis are acrosome development, head shaping, and growth of the sperm flagellum [5,6] These events are critically reliant upon complex microtubule structures, including the manchette and the axoneme, and a highly orchestrated series of protein transport mechanisms [7]. We note that dynamic redistribution of the actin cytoskeletal system is required for normal manchette function [8]

Methods

Results

Discussion

Conclusion