title: The onset of heat-induced testicular calcification in mice: involvement of the telomeric locus on chromosome 1.
abstract: Spermatocytes of MRL/MpJ mice are more heat resistant than those of C57BL/6 mice in experimental cryptorchidism. This phenotype depends in part on the locus at the 81-cM region of MRL/MpJ-type chromosome 1 (Chr 1). To evaluate the function of this locus, we examined pathological changes in mouse testes resulting from transient scrotal heat stress. Immediately after scrotal heat stress, meiosis progression and blood-testis barrier integrity were preserved in MRL/MpJ but not in C57BL/6 mice, nor in a C57BL/6-based congenic strain carrying the MRL/MpJ-derived Chr 1 locus (B6.MRLc1). Testicular damage was severe in the weeks after scrotal heat stress in all three strains; however, testicular calcification was observed only in C57BL/6 and MRL/MpJ mice (initially as nanocrystals in mitochondria of degenerating germ cells). In testes, expression of gremlin 2, a bone morphogenetic protein antagonist encoded on Chr 1, was markedly higher in B6.MRLc1 than in C57BL/6 or MRL/MpJ mice. Furthermore, gremlin-2 and bone morphogenetic protein 2 mRNA levels in heated testes correlated negatively and positively, respectively, with calcification. Thus, although the MRL/MpJ-derived locus on Chr 1 may play a pivotal role in recovery from heat-induced testicular damage, especially via inhibition of calcification, MRL/MpJ mice have a precipitating factor for testicular calcification and heat shock-resistant factors that reside outside the 81-cM region of Chr 1.
authors.affiliation: Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Chihara
authors.affiliation: Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan; Section of Biological Safety Research, Chitose Laboratory, Japan Food Research Laboratories, Chitose, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Section of Inorganic Analysis II, Tama Laboratory, Japan Food Research Laboratories, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sakakibara
authors.affiliation: Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Otsuka
authors.affiliation: Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ichii
authors.affiliation: Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan. Electronic address: y-kon@vetmed.hokudai.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kon
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002114:Calcinosis / Q000235:genetics* / Q000473:pathology*; D033481:Chromosomes, Mammalian / Q000235:genetics*; D016207:Cytokines; D006358:Hot Temperature / Q000009:adverse effects; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011506:Proteins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016615:Telomere / Q000235:genetics*; D013737:Testis / Q000473:pathology*
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D016207:Cytokines; C490088:Grem2 protein, mouse; D011506:Proteins