The Impact of Long-Term Exposure to Space Environment on Adult Mammalian Organisms: A Study on Mouse Thyroid and Testis

Abstract

Hormonal changes in humans during spaceflight have been demonstrated but the underlying mechanisms are still unknown. To clarify this point thyroid and testis/epididymis, both regulated by anterior pituitary gland, have been analyzed on long-term space-exposed male C57BL/10 mice, either wild type or pleiotrophin transgenic, overexpressing osteoblast stimulating factor-1. Glands were submitted to morphological and functional analysis.In thyroids, volumetric ratios between thyrocytes and colloid were measured. cAMP production in 10−7M and 10−8M thyrotropin-treated samples was studied. Thyrotropin receptor and caveolin-1 were quantitized by immunoblotting and localized by immunofluorescence. In space-exposed animals, both basal and thyrotropin-stimulated cAMP production were always higher. Also, the structure of thyroid follicles appeared more organized, while thyrotropin receptor and caveolin-1 were overexpressed. Unlike the control samples, in the space samples thyrotropin receptor and caveolin-1 were both observed at the intracellular junctions, suggesting their interaction in specific cell membrane microdomains.In testes, immunofluorescent reaction for 3β- steroid dehydrogenase was performed and the relative expressions of hormone receptors and interleukin-1β were quantified by RT-PCR. Epididymal sperm number was counted. In space-exposed animals, the presence of 3β and 17β steroid dehydrogenase was reduced. Also, the expression of androgen and follicle stimulating hormone receptors increased while lutenizing hormone receptor levels were not affected. The interleukin 1 β expression was upregulated. The tubular architecture was altered and the sperm cell number was significantly reduced in spaceflight mouse epididymis (approx. −90% vs. laboratory and ground controls), indicating that the space environment may lead to degenerative changes in seminiferous tubules.Space-induced changes of structure and function of thyroid and testis/epididymis could be responsible for variations of hormone levels in human during space missions. More research, hopefully a reflight of MDS, would be needed to establish whether the space environment acts directly on the peripheral glands or induces changes in the hypotalamus-pituitary-glandular axis.

Cytokine Release and Focal Adhesion Proteins in Normal Thyroid Cells Cultured on the Random Positioning Machine

“…The objective of this project was to monitor changes occurring during short-term RPM-exposure in normal human thyrocytes with respect to the influence of soluble factors on proteins involved in focal adhesion. These findings might help to further understand the observed impact of microgravity on the formation of 3D aggregates of normal human thyrocytes and other cells [4, 5]. …”

“…There are reports about various health concerns such as dysfunctions of the musculoskeletal and cardiovascular system, a down-regulation of the immune system, and visual problems [1-3]. In space, the thyroid gland in vivo revealed a variety of changes such as follicles with larger thyrocytes and increases in cAMP, thyrotropin-receptors (TSHR), and caveolin-1 [4, 5]. On the cellular level, it is known that both real (r-µ g ) and simulated microgravity (s-µ g ) influence growth behaviour, gene expression pattern, protein synthesis and secretion in thyroid cancer cells [6-11].…”

Spaceflight Influences both Mucosal and Peripheral Cytokine Production in PTN-Tg and Wild Type Mice

“…Details regarding the mouse drawer system and exposure of C57BL/10J Wt and PTN-Tg mice to zero gravity on the ISS have been previously described in “The Mice Drawer System Experiment and the Space Endurance Record-Breaking Mice” (2012) PLoS Collections [8], [11], [49], [50], [51]. Mice were 8 weeks old at launch.…”

Growing Tissues in Real and Simulated Microgravity: New Methods for Tissue Engineering

“…121 Overall, obvious differences in the thyroid tissue structure could be detected. 122,123 Investigating the effects generated by an RPM, changes in the cytoskeleton, the ECM, and in apoptosis of human thyroid cells were observed. 10,124,125 By proteome analyses, normal and cancerous thyroid-cell-dependent changes in the content of regulatory, metabolic, and structural proteins could be detected.…”