The Effects of Vitamin D3 Supplementation and Simultaneous Exercise on Aldehyde Dehydrogenase Gene Expression in Endometriosis Female Rats

The variable investigated in this research was ALDH1A2, which decreased under the influence of vitamin D3 and endurance and resistance exercises in the supplement and exercise groups. One of the discussed mechanisms is the role of the ALDH gene in the detoxification of produced aldehydes and the oxidation of aldehydes to carboxylic acids. The results of Yildirim et al.’s studies also were similar to the findings of this research ( 16). Probably, the production of ALDH1A2 is inversely related to the increased expression of cytochrome P450. The decrease of this enzyme leads to decreasing the alpha-retinoic acid receptor, and finally, estradiol increases epithelial endometriosis. The secretion of this enzyme is active under normal oxygen conditions and catalyzes the conversion of nitrate compounds into nitric oxide, so it is natural that with the increase of these aldehydes, endometriosis increases; consequently, the changes in ALDH2 activity may be the basis of endometriosis disease pathology. The increase in ALDH2 activity reduces the allogenic input to the central nervous system by sensory afferents of the lesion to reduce pain. Therefore, the reduction of this enzyme in the supplement and exercise groups compared to the endometriosis group is a sign of lesion reduction ( 17). According to the available reports, vitamin D3 reduces the growth and implantation of endometrial tissue, and the abnormal concentration of vitamin D3 causes the incomplete removal of endometrial cells passing through the peritoneum and ovarian reflux, which is another effective mechanism in the results of this research ( 17). In Chung et al.’s research, high levels of vitamin D3 and calcium have been confirmed in endometriosis ( 18). A serum concentration of more than 70 ng/mL increases the growth of endometriosis, which is contrary to the results of this research. High levels of calciferol increase the risk of endometriosis, but in cysts that have already developed, it is a strong inhibitor of re-angiogenesis ( 19, 20). In addition, hypovitaminosis D3 is also a potential risk factor for endometriosis. Exercise may help improve endometriosis symptoms (reduced menstrual cycles and bleeding between periods, reduced pain and constipation, increased energy, and improved sleep). The effect of physical activity on endometriosis is through the effect of endorphins as a natural painkiller. It also boosts mood and controls anxiety and depression, likely due to the constant pain and changing hormones, and increased estrogen levels in endometriosis. Lack of sleep can increase inflammation and anxiety and worsen endometriosis. It can be said that endometriosis is related to pelvic floor dysfunction. Sports activities, particularly resistance exercises, improve the strength and condition of body muscles. Increasing mobility through endurance activities relaxes muscles and reduces hip pain. There are also reports of the management of gastrointestinal symptoms of constipation, bloating, and irritable bowel syndrome with exercise. Some research has linked fatigue to endometriosis. Fatigue is often associated with sleep problems, depression, and pain. However, staying active helps some women regain their energy. Body movement increases blood flow, which equals more energy. These results are consistent with the findings of Tibana et al.'s study ( 15). The results of Ghasemian et al.’s study investigating the effects of aerobic swimming and vitamin B6 on the GATA index ( 21) are inconsistent with the findings of the present study by reporting that regular aerobic exercise, as well as co-administration of vitamin B6, may affect GATA2 gene expression ( 20). Chung et al. have shown that a diet rich in vitamins and antioxidants is effective in the metastasis and growth of endometriosis ( 18). Of course, the antioxidant and anti-inflammatory roles of vitamin D3 and its contribution to strengthening the immune system can be effective in reducing endometriosis ( 20). In this regard, it can be said that endometriosis feeds the estrogen hormone and leads to inflammation, bloating, and pelvic pain, but exercise helps reduce estrogen. Reducing the risk of endometriosis and focusing on exercise are useful approaches, causing the release of myokines from the muscles. These results are consistent with the findings of Augostinis et al.’s study ( 22). In addition, exercise increases the production of leukocytes, cortisol, and adrenaline, all of which have metabolic, neurological, and inflammatory effects ( 23). There is a relationship between regular and vigorous exercise and its effect on health ( 24). Progressive overload in sports has stronger effects, and a reduction in stress levels has been reported ( 25). Moreno et al. also achieved these results in their research. Pelvic floor muscle tension in women with endometriosis pain is higher than the control group without endometriosis ( 26). Which are possibly effective mechanisms for reducing endometriosis in this research? There is still no definitive treatment for endometriosis, and the main focus is on pain control and hormonal suppression. The role of physical activity and exercise has been suggested as part of the therapeutic approach. Inflammation caused by endometriosis sensitizes pelvic organs ( 13, 27); although inflammatory factors were not investigated in this research, physical activity is acceptable to reduce inflammation, prevent disease progression, and improve pain ( 28). The type, intensity, and duration of exercise, medical history, and the type and amount of vitamins and supplements consumed seem to be effective on the severity of endometriosis and the differences in findings. Therefore, exercise and supplements can contribute to reducing and stopping endometriosis. At present, the cause and initial history of endometriosis are not clear, treatment methods are few, and no definitive treatment has been recognized for this disabling disease. However, it is known that angiogenesis considerably contributes to endometriosis pathogenesis ( 13, 27). Angiogenesis inhibitors have been indeed suggested as a new treatment method for this disease, as they have been demonstrated to suppress endometriotic lesion growth in an animal model ( 28). It is worth mentioning that using cDNA microarrays for the investigation of endometriosis encounters some restrictions. Endometriosis tissue is heterologous, i.e., it consists of a combination of endometrium, myometrium, serosa, connective tissue, and immune cells. Hence, no one can guarantee that the profiles of the current study’s gene expression stem from a tissue that contributes to the pathophysiology of this disease).