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Infertility and Testicular Defects in Hormone-Sensitive Lipase-Deficient Mice

Infertility and Testicular Defects in Hormone-Sensitive Lipase-Deficient Mice,SHARI CHUNG,SHU PEI WANG,LINGE PAN,GRANT MITCHELL,JACQUETTA TRASLER,LOUI

Infertility and Testicular Defects in Hormone-Sensitive Lipase-Deficient Mice   (Citations: 14)
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The 84-kDa hormone-sensitive lipase (gene designation Lipe ;E C 3.1.1.3) is a cholesterol esterase and triglyceride hydrolase that functions in the release of fatty acids from adipocytes. The role of hormone-sensitive lipase in other tissues such as the testis, where a specific 120-kDa testis-specific isoform is expressed, is unknown. To study this, we examined the fertility and testicular histology of gene-targeted hormone-sensitive lipase-deficient mice. Homozygous hormone-sensitive lipase-deficient male mice are infertile and have decreased testis weights; female ho- mozygotes are fertile. Testicular abnormalities, detected at the light and electron microscopic levels, included the presence of multinucleated round and elongating spermatids, vacuolization of the seminiferous epithelium, asynchronization of the sper- matogenic cycle, sloughing of postmeiotic germ cells from the seminiferous epithelium into the lumen, and a marked reduc- tion in the numbers of late spermatids. Extensive nuclear head deformation was noted in late spermatids as well as the sharing of a common acrosome in multinucleated cells. In some multinu- cleated cells, nuclei were separated from their acrosomes, with the acrosomes remaining attached to areas of ectoplasmic spe- cializations, suggesting defects in intercellular cytoplasmic bridge integrity. Although the lumen of the epididymis was es- sentially devoid of spermatozoa and filled instead with spherical degenerating cells, the epididymal epithelial cells appeared nor- mal. The few late spermatids present in the epididymis were abnormal. There was no morphological evidence, as judged by the absence of lipid droplets of triacylglycerol or cholesteryl ester accumulation in the testis. Together, the data suggest that hormone-sensitive lipase deficiency results in abnormalities in spermiogenesis that are incompatible with normal fertility. We speculate that a metabolite downstream from the hormone- sensitive lipase reaction may be essential for membrane stabi- lization and integrity in the seminiferous epithelium and, in particular, may play an important role in the maintenance of intercellular cytoplasmic bridges between postmeiotic germ cells. (Endocrinology 142: 4272-4281, 2001)
Published in 2010.
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    • ... Other aspects of its phenotype in mice include male infertilit...

    G A Mitchell. Genetics, physiology and perinatal influences in childhood obesity: vi...

    • ...In the testes, cholesterol/esterified cholesterol ratio is argued to manipulate normal spermiogenesis process [20]...

    Li Zhanget al. Baculo-expression and enzymatic characterization of CES7 esterase

    • ...in glucose-stimulated insulin secretion in pancreatic beta cells (Roduit et al., 2001), cholesteryl ester hydrolysis in the adrenal gland (Li et al., 2001) and somewhatsurprisingly,asanessentialelementformale fertility (Osuga et al., 2000; Chung et al., 2001)...
    • ...These included a disruption of the intercellular bridges of spermatids resulting in multinucleation of these cells, abnormal shapes of the head and acrosome of elongating spermatids, an apparent reduction of elongating spermatids (steps 9‐16), and sloughing of round spermatids into the lumen, which could subsequently be identified in the epididymal lumen (Chung et al., 2001)...
    • ...The generationofmicewithatargeteddisruptionoftheLipe gene encoding HSL has been reported; these mice have no detectable HSL activity or protein in any tissue including testis (Chung et al., 2001)...
    • ...Mice were genotyped by PCR analysis of tail DNA as described previously (Chung et al., 2001)...
    • ...Electron microscopy confirmed the light microscopic observations and were comparable to those already amplydescribedinourearlierworkon6-month-oldmice (Chung et al., 2001)...
    • ...vacuolations were not observed (Chung et al., 2001)...
    • ...Osuga et al. (2000) and our group (Chung et al., 2001) showed that HSL� /� mice lack cholesteryl ester hydro-...
    • ...In addition, an effect on spermatid cell membrane integrity may also explain the sloughing of such cells from the seminiferous epithelium into the epididymal lumen, as noted in this and our previous study (Chung et al., 2001)...
    • ...Since previous studies dealt with animals at 6 months of age (Chung et al., 2001) and HSL� /� mice appear to be infertile irrespective...

    Louis Hermoet al. Alterations in the testis of hormone sensitive lipase-deficient mice i...

    • ...They occur occasionally in the testis of normal animals and are generated in large numbers due to various disorders and male reproductive toxicants (50), and in transgenic mice such as sys (symplastic spermatids) (53, 54) and those deficient in BAX (55) and HSL (56)...

    Faridha Aet al. DURATION-DEPENDENT HISTOPATHOLOGICAL AND HISTOMETRIC CHANGES IN THE TE...

    • ...One exception was the testis, which was 30% smaller in HSL/ mice than in HSL/ mice under both normal chow and high-fat conditions, consistent with previous reports of severe oligo/azospermia in HSL/ mice (3, 27)...

    Kenji Haradaet al. Resistance to high-fat diet-induced obesity and altered expression of ...

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