title: Manchette-acrosome disorders during spermiogenesis and low efficiency of seminiferous tubules in hypercholesterolemic rabbit model.
abstract: Hypercholesterolemia is a marker for several adult chronic diseases. Recently we demonstrated that sub/infertility is also associated to Hypercholesterolemia in rabbits. Seminal alterations included: abnormal sperm morphology, decreased sperm number and declined percentage of motile sperm, among others. In this work, our objective was to evaluate the effects of hypercholesterolemia on testicular efficiency and spermiogenesis, as the latter are directly related to sperm number and morphology respectively. Tubular efficiency was determined by comparing total number of spermatogenic cells with each cell type within the proliferation/differentiation compartments. We found lower testicular efficiency related to both a decrease in spermatogonial cells and an increase in germ cell apoptosis in hypercholesterolemic rabbits. On the other hand, spermiogenesis-the last step of spermatogenesis involved in sperm shaping-was detaily analyzed, particularly the acrosome-nucleus-manchette complex. The manchette is a microtubular-based temporary structure responsible in sperm cell elongation. We analyzed the contribution of actin filaments and raft microdomains in the arrangement of the manchette. Under fluorescence microscopy, spermatocyte to sperm cell development was followed in cells isolated from V to VIII tubular stages. In cells from hypercholesterolemic rabbits, abnormal development of acrosome, nucleus and inaccurate tail implantation were associated with actin-alpha-tubulin-GM1 sphingolipid altered distribution. Morphological alterations were also observed at electron microscopy. We demonstrated for the first time that GM1-enriched microdomains together with actin filaments and microtubules are involved in allowing the correct anchoring of the manchette complex. In conclusion, cholesterol enriched diets promote male fertility alterations by affecting critical steps in sperm development: spermatogenesis and spermiogenesis. It was also demonstrated that hypercholesterolemic rabbit model is a useful tool to study serum cholesterol increment linked to sub/infertility.
authors.affiliation: Laboratorio de Investigaciones Andrológicas de Mendoza (LIAM). Instituto y Área de Histología y Embriología (IHEM), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo y Centro Científico Tecnológico (CCT), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina.|Instituto de investigaciones. Facultad de Ciencias Médicas. Universidad del Aconcagua. Mendoza, Argentina.
authors.forename: Layla
authors.initials: L
authors.lastname: Simón
authors.affiliation: Laboratorio de Investigaciones Andrológicas de Mendoza (LIAM). Instituto y Área de Histología y Embriología (IHEM), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo y Centro Científico Tecnológico (CCT), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina.
authors.forename: Abi K
authors.initials: AK
authors.lastname: Funes
authors.affiliation: Laboratorio de Investigaciones Andrológicas de Mendoza (LIAM). Instituto y Área de Histología y Embriología (IHEM), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo y Centro Científico Tecnológico (CCT), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina.
authors.forename: Martín A
authors.initials: MA
authors.lastname: Yapur
authors.affiliation: Laboratorio de Investigaciones Andrológicas de Mendoza (LIAM). Instituto y Área de Histología y Embriología (IHEM), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo y Centro Científico Tecnológico (CCT), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina.|Instituto de investigaciones. Facultad de Ciencias Médicas. Universidad del Aconcagua. Mendoza, Argentina.
authors.forename: María E
authors.initials: ME
authors.lastname: Cabrillana
authors.affiliation: Laboratorio de Investigaciones Andrológicas de Mendoza (LIAM). Instituto y Área de Histología y Embriología (IHEM), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo y Centro Científico Tecnológico (CCT), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina.|Instituto de investigaciones. Facultad de Ciencias Médicas. Universidad del Aconcagua. Mendoza, Argentina.
authors.forename: María A
authors.initials: MA
authors.lastname: Monclus
authors.affiliation: Laboratorio de Investigaciones Andrológicas de Mendoza (LIAM). Instituto y Área de Histología y Embriología (IHEM), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo y Centro Científico Tecnológico (CCT), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina.|Instituto de investigaciones. Facultad de Ciencias Médicas. Universidad del Aconcagua. Mendoza, Argentina.
authors.forename: Paola V
authors.initials: PV
authors.lastname: Boarelli
authors.affiliation: Laboratorio de Investigaciones Andrológicas de Mendoza (LIAM). Instituto y Área de Histología y Embriología (IHEM), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo y Centro Científico Tecnológico (CCT), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Vincenti
authors.affiliation: Laboratorio de Investigaciones Andrológicas de Mendoza (LIAM). Instituto y Área de Histología y Embriología (IHEM), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo y Centro Científico Tecnológico (CCT), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina.|Instituto de investigaciones. Facultad de Ciencias Médicas. Universidad del Aconcagua. Mendoza, Argentina.
authors.forename: Tania E
authors.initials: TE
authors.lastname: Saez Lancellotti
authors.affiliation: Laboratorio de Investigaciones Andrológicas de Mendoza (LIAM). Instituto y Área de Histología y Embriología (IHEM), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo y Centro Científico Tecnológico (CCT), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina.|Instituto de investigaciones. Facultad de Ciencias Médicas. Universidad del Aconcagua. Mendoza, Argentina.
authors.forename: Miguel W
authors.initials: MW
authors.lastname: Fornés
mesh_terms: D000177:Acrosome / Q000473:pathology*; D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002784:Cholesterol / Q000097:blood; D003599:Cytoskeleton / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000737:chemistry; D005854:Germ Cells / Q000473:pathology; D006937:Hypercholesterolemia / Q000150:complications / Q000503:physiopathology*; D007248:Infertility, Male / Q000150:complications / Q000503:physiopathology; D008297:Male; D021962:Membrane Microdomains / Q000737:chemistry; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism; D023421:Models, Animal; D011817:Rabbits; D012671:Seminiferous Tubules / Q000503:physiopathology*; D013082:Sperm Tail / Q000378:metabolism; D013087:Spermatids / Q000473:pathology; D013090:Spermatocytes / Q000166:cytology; D013091:Spermatogenesis; D013094:Spermatozoa / Q000473:pathology*; D013737:Testis / Q000502:physiology; D014404:Tubulin / Q000378:metabolism
chemical_list: D014404:Tubulin; D005677:G(M1) Ganglioside; D002784:Cholesterol