ИСТИНА

The major microgravity “targets”, the muscle, the bone and cardiovascular system, display functional differences in male and female individuals governed largely by the pleiotropic effects of sex steroids. However, sex differences in adaptation of different tissues to microgravity are poorly studied. Aiming to investigate sex differences in the reaction of mammals to microgravity, we have we estimated the degree of bone loss, muscle loss and myosin phenotype shift, as well as the red blood parameters in mice subject to 30 days of hindlimb unloading (HLU) or a control exposure of attached mice without actual unloading (ATT). HLU is known to decrease testosterone and estrogen levels in males and females, correspondingly. To overcome this limitation, we used gonadectomized mice with or without the sex-specific hormonal supplementation to create a model with experimentally controlled hormone levels; additional groups were left gonadally intact to illustrate the deteriorative HLU effect on sex steroid level. Testosterone levels and m. bulbocavernosus mass were expectedly reduced with castration and restored with testosterone propionate supplementation. Both estimates of androgen levels were greatly reduced in gonadally intact HLU males as compared to ATT counterparts. Similarly, estradiol and uterus weight dropped in ovariectomized females and were restored with estradiol benzoate. Uterine weight and serum estradiol were reduced in gonadally intact HLU females as compared to ATT mice. Adrenal weights and corticosterone levels were similar in HLU and ATT mice. In summary, the use of animals with experimentally controlled hormone levels is prerequisite for studies of sex-differences in the hindlimb unloading model. M. soleus, smaller in females, than in males, after 30 days of unloading lost its mass uniformly in both sexes. Experimental manipulations of the hormonal status did not affect m. soleus mass. M. gastrocnemius mass varied with sex and HLU, but the degree of m. gastrocnemius mass loss (single digit percent) was much less pronounced as compared to m. soleus. No evidence of HLU-induced training was found in m. triceps brachii, while m. masseter mass was similar in all the groups. The percentage of fast and slow myosin positive fibers in m. soleus was not affected by the unloading, sex or the hormonal status of the subjects, while the intermediate fibers number increased roughly twofold in both male and female hindlimb- unloaded mice. The fiber cross-sectional area was higher in males as compared to females and was reduced with the unloading, particularly in the hormonally competent sham-operated and gonadectomized, hormonally replaced male and female mice. BMD, an integral measure of the cancellous bone mineral content, was reduced after 30 days of HLU. The effects of the animals’ sex and the hormonal status were highly significant as well. BMD reduction in HLU mice as compared to ATT animals was more pronounced in the females. In the males, only the gonadally intact HLU mice displayed BMD loss comparable to females, presumably, due to the decrease in testosterone. The animals’ sex, hormonal status and HLU had a significant effect on bone volume, similarly to the pattern of BMD changes. Both, density and thickness of the trabeculae were significantly reduced with HLU. In summary, the relative bone loss was more pronounced in female mice and was governed by reduction of the trabeculae linear density and thickness. Hematological parameters displayed expected sex-related differences but were not affected by HLU. In summary mice display tissue-specific sex differences in reaction to microgravity simulated with 30-days hindlimb unloading. Further experimental research is needed to investigate if the gravitational physiology concepts, derived from experiments performed mostly on male subjects, are equally applicable to female space travelers.