The Onset of Heat-Induced Testicular Calcification in Mice

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.

Changes in Levels of Seminal Nitric Oxide Synthase, Macrophage Migration Inhibitory Factor, Sperm DNA Integrity and Caspase-3 in Fertile Men after Scrotal Heat Stress

“…Local testicular heat treatment with 43°C water induced reversible oligospermia or azoospermia in rodents and monkeys with increased germ cell apoptosis [ 31 – 36 ], and when the heat treatment stopped after 30 days, the sperm quantity could recover to the original level. The heat treatment of the scrotum was mainly through the impact on the metabolism and apoptosis of spermatogenic cells to decline the fertility of many kinds of animal models; moreover, this impact was temporary and reversible [ 32 – 40 ].…”

Ovarian mast cells migrate toward ovary-fimbria connection in neonatal MRL/MpJ mice

“…We have previously reported that the autoimmune disease models, MRL/MpJ and their mutant strain MRL/MpJ- Fas lpr/lpr mice, have unique phenotypes in the reproductive organs, such as metaphase-specific apoptosis of meiotic spermatocytes [ 11 – 13 ], heat shock resistance of spermatocytes found in experimental cryptorchidism [ 14 , 15 ], testicular calcification after transient scrotal heat stress [ 16 , 17 ], existence of testicular oocytes in newborn males [ 18 , 19 ], and development of ovarian cysts originating from the rete ovarii [ 20 ]. In addition, female MRL/MpJ- Fas lpr/lpr mice show abnormal reproductive processes [ 21 , 22 ], indicating that these mouse strains are useful models for reproductive immunology.…”