Effects and potential mechanism of hypoxia on vitamin D metabolism in pregnant SD rats
Objective To investigate the effects and potential mechanism of hypoxia on vitamin D metabolism in pregnant SD rats.Methods Twenty adult female SD rats were divided into two groups∶normoxia group(8 rats)and hypoxia group(12 rats).Ten adult male SD rats were housed together with the above two groups of female rats in a 2∶1 ratio to establish a pregnancy model.The metabolic level of serum vitamin D in female rats was detected by ELISA.Real-time qPCR was used to analyze the expression of vitamin D metabolism-related genes in the liver,kidney and placenta.The morphology of placenta was observed and analyzed by HE staining and immunohisto-chemical sections.Results The content of serum vitamin D metabolic active substance 25(OH)2D3 in normoxia group was lower than that in hypoxia group,and the difference was statistically significant(P<0.05).The metabolic level of hypoxia group was increased.Real-time qPCR results showed that under hypoxic conditions,the expression of CYP2R1 in the liver was up-regulated(P<0.05),the expression of CYP27B1 in the kidney was up-regulated(P<0.05),and the expression of CYP24A1 in the kidney was down-regulated(P<0.05).There was no significant difference in CYP2R1 and CYP27B1 in placenta between the two groups(P>0.05).The results of immunohisto-chemistry of placenta showed that the expression of CYP2R1 and CYP27B1 in placenta was increased in hypoxia group compared with normoxia group(P<0.05),while the expression of CYP24A1 decreased(P<0.05).The three proteins were mainly expressed in placental trophoblast cells.Form the results of placental HE staining sections,it can be seen that there was no significant variation in the morphology of placenta in normoxia group and hypoxia group.Conclusions Hypoxia can accelerate the metabolism of vitamin D in pregnant rats.The mechanism may be that hypoxia increases the metabolism of vitamin D in the liver,kidney and placenta,while destroys the negative feedback mechanism of vitamin D mediated by CYP24A1.There are vitamin D metabolic system and autocrine regu-latory system in placental trophoblast cells,and trophoblast cells may be the source of 1,25(OH)2D3 in pregnant rats.
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