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

Liu Y, DeBoer K, de Kretser DM, O'Donnell L, O'Connor AE, Merriner DJ, Okuda H, Whittle B, Jans DA, Efthymiadis A, McLachlan RI, Ormandy CJ, Goodnow CC, Jamsai D, O'Bryan MK - PLoS Genet. (2015)

Bottom Line: The most common pathology is a complex presentation of decreased sperm output and abnormal sperm shape and motility referred to as oligoasthenoteratospermia (OAT).Manchette dysfunction leads to abnormal sperm head shaping.Several of these functions may be achieved in association with the LRGUK-1 binding partner HOOK2.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Australia.

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.

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Related in: MedlinePlus

Acrosome and manchette defects in LrgukKaos/Kaos mice.(A) PAS stained testis sections from LrgukWT/WT and LrgukKaos/Kaos mice. Arrows indicate mis-localised proacrosomal vesicles. (B) Transmission electron microscopy of elongated spermatid from LrgukWT/WT and LrgukKaos/Kaos mice. The green arrow indicates a detached acrosome. Nu = nucleus. Scale bar = 2μm. (C) Transmission electron microscopy showing abnormal manchette structure including a constricted perinuclear ring (green arrow). Red arrows indicate microtubules within the manchette.
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pgen.1005090.g004: Acrosome and manchette defects in LrgukKaos/Kaos mice.(A) PAS stained testis sections from LrgukWT/WT and LrgukKaos/Kaos mice. Arrows indicate mis-localised proacrosomal vesicles. (B) Transmission electron microscopy of elongated spermatid from LrgukWT/WT and LrgukKaos/Kaos mice. The green arrow indicates a detached acrosome. Nu = nucleus. Scale bar = 2μm. (C) Transmission electron microscopy showing abnormal manchette structure including a constricted perinuclear ring (green arrow). Red arrows indicate microtubules within the manchette.

Mentions: One of the features of the LrgukKaos/Kaos phenotype was the abnormal morphology of sperm heads. A detailed analysis of acrosome formation on periodic acid Schiff’s (PAS) stained sections revealed the presence of fragmented acrosomes in step 2–4 spermatids (Fig. 4A). The acrosome is formed by the sequential fusion of Golgi-derived pro-acrosomal vesicles to form a cap overlying the nucleus. The membrane overlying the acrosome is essential for the initial binding to and penetration through the oocyte complex [15,24,25]. Electron microscopy also revealed ∼20% of acrosomes in elongated spermatids were detached from sperm nuclei (Fig. 4B). A close inspection of these cells indicated that both the acrosome and the acroplaxome were detaching from the nuclear membrane suggesting that LRGUK-1 has a role in establishing the integrity of the connection between the acroplaxome and the nuclear membrane.


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

Liu Y, DeBoer K, de Kretser DM, O'Donnell L, O'Connor AE, Merriner DJ, Okuda H, Whittle B, Jans DA, Efthymiadis A, McLachlan RI, Ormandy CJ, Goodnow CC, Jamsai D, O'Bryan MK - PLoS Genet. (2015)

Acrosome and manchette defects in LrgukKaos/Kaos mice.(A) PAS stained testis sections from LrgukWT/WT and LrgukKaos/Kaos mice. Arrows indicate mis-localised proacrosomal vesicles. (B) Transmission electron microscopy of elongated spermatid from LrgukWT/WT and LrgukKaos/Kaos mice. The green arrow indicates a detached acrosome. Nu = nucleus. Scale bar = 2μm. (C) Transmission electron microscopy showing abnormal manchette structure including a constricted perinuclear ring (green arrow). Red arrows indicate microtubules within the manchette.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4363142&req=5

pgen.1005090.g004: Acrosome and manchette defects in LrgukKaos/Kaos mice.(A) PAS stained testis sections from LrgukWT/WT and LrgukKaos/Kaos mice. Arrows indicate mis-localised proacrosomal vesicles. (B) Transmission electron microscopy of elongated spermatid from LrgukWT/WT and LrgukKaos/Kaos mice. The green arrow indicates a detached acrosome. Nu = nucleus. Scale bar = 2μm. (C) Transmission electron microscopy showing abnormal manchette structure including a constricted perinuclear ring (green arrow). Red arrows indicate microtubules within the manchette.
Mentions: One of the features of the LrgukKaos/Kaos phenotype was the abnormal morphology of sperm heads. A detailed analysis of acrosome formation on periodic acid Schiff’s (PAS) stained sections revealed the presence of fragmented acrosomes in step 2–4 spermatids (Fig. 4A). The acrosome is formed by the sequential fusion of Golgi-derived pro-acrosomal vesicles to form a cap overlying the nucleus. The membrane overlying the acrosome is essential for the initial binding to and penetration through the oocyte complex [15,24,25]. Electron microscopy also revealed ∼20% of acrosomes in elongated spermatids were detached from sperm nuclei (Fig. 4B). A close inspection of these cells indicated that both the acrosome and the acroplaxome were detaching from the nuclear membrane suggesting that LRGUK-1 has a role in establishing the integrity of the connection between the acroplaxome and the nuclear membrane.

Bottom Line: The most common pathology is a complex presentation of decreased sperm output and abnormal sperm shape and motility referred to as oligoasthenoteratospermia (OAT).Manchette dysfunction leads to abnormal sperm head shaping.Several of these functions may be achieved in association with the LRGUK-1 binding partner HOOK2.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Australia.

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.

Show MeSH
Related in: MedlinePlus