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Further studies on knockout mice lacking a functional dynein heavy chain (MDHC7). 2. A developmental explanation for
David M Woolley1, Juergen Neesen, Geraint G Vernon
1Department of Physiology, School of Medical Sciences, University of Bristol, United Kingdom. D.M.Woolley@bristol.ac.uk
Abstract:
Male mice had been previously generated in which the inner dynein arm heavy chain 7 gene (MDHC7) was disrupted. MDHC7-/- animals show asthenozoospermia and are sterile. Very few of their spermatozoa can achieve forward progression, but for those that can, we add here the information (1) that the three-dimensional aspects of their movement are normal; (2) that their maximum velocity is less than that of wild-type controls; and (3) that they are entirely unable to penetrate media of raised viscosity (25-4,000 cP). However, the large majority of the spermatozoa can achieve only a low amplitude vibration. In these sperm we find, using electron microscopy, that the outer dense fibres retain attachments to the inner surface of the mitochondria. Such attachments are present in normal epididymal mouse spermatozoa but are broken down as soon as the sperm become motile on release from the epididymis. The attachments are presumed to be essential during midpiece development and, afterwards, to require a threshold level of force to loosen them and so permit the sliding displacements necessary for normal bending. We presume that the disruption of the inner dynein arm heavy chain gene, MDHC7, means that there is insufficient force to overcome the attachments, for all but a few spermatozoa.
Insights
Disrupting the inner dynein arm heavy chain 7 gene (MDHC7) in mice causes sterility due to sperm motility defects. Unbroken mitochondrial attachments in sperm prevent normal flagellar bending and forward progression.
Area of Science:
- Spermatogenesis and sperm motility research
- Molecular genetics and reproductive biology
Background:
- The inner dynein arm heavy chain 7 (MDHC7) gene is crucial for sperm function.
- MDHC7 knockout mice exhibit asthenozoospermia and sterility.
Purpose of the Study:
- To investigate the detailed motility characteristics of MDHC7-deficient spermatozoa.
- To elucidate the structural basis for impaired sperm motility in MDHC7-/- mice.
Main Methods:
- Generation of MDHC7 knockout mice (MDHC7-/-).
- Analysis of sperm motility parameters, including velocity and movement in viscous media.
- Electron microscopy to examine sperm ultrastructure, focusing on outer dense fibres and mitochondrial attachments.
Main Results:
- MDHC7-/- mice are sterile with severely impaired sperm motility (asthenozoospermia).
- Motile sperm from MDHC7-/- mice show normal 3D movement aspects but reduced velocity.
- Sperm from MDHC7-/- mice cannot penetrate viscous media and exhibit persistent outer dense fibre attachments to mitochondria.
Conclusions:
- Deficiency in MDHC7 disrupts sperm motility by preventing the breakdown of mitochondrial attachments.
- These attachments appear to impede flagellar bending, requiring sufficient force to detach for normal motility.
- MDHC7 is essential for generating the force needed to overcome these attachments, ensuring sperm motility and fertility.
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