Abstract:
Objective To investigate the effects of maternal hypoxia on the expression of growth factors,extracellular matrix and morphological changes of carotid arteries from fetal rabbit. Methods Ten New Zealand White rabbits were randomly divided into 2groups:perinatal hypoxia(12% O
2,n=5)and normoxic control(21% O
2,n=5).Rabbits in hypoxia group were put into the hypoxia box for low oxygen exposure,twice a day(morning and affernoon)and four hours per time,from pregnancy day 10 to 29. At the end of pregnancy(29-day gestation),Western blot was used to determine hypoxia-inducible factor-1(HIF-1α),transforming growth factorβ
1(TGF-β
1),Smad3 and connective tissue growth factor(CTGF)expression in carotid arteries of fetuses,and real-time polymerase chain reaction(RT-PCR)was performed to evaluate HIF-1α,TGF-β
1and CTGF mRNA concentrations. Masson’s trichrome staining was employed to examine collagen or elastin content,and immunohistochemistry was performed to detect TGF-β
1,CTGF,CollⅠ and CollⅢ protein expression in the isolated rings from arteries of fetuses respectively.Results Notably,hypoxia treatment induced a significant increase in protein level in HIF-1α(0.26±0.05 vs 0.07±0.04),TGF-β
1(0.68±0.08 vs 0.51±0.11),Smad3(0.47±0.04 vs 0.26±0.02)and CTGF(0.81±0.09 vs 0.53±0.12),and mRNA level in HIF-1α(1.62±0.37 vs 1.00±0.18),TGF-β
1(1.90±0.35 vs 1.00±0.12)and CTGF(1.82±0.42 vs 1.00±0.21),which were associated with the elevation of TGF-β
1,CTGF,collagenⅠ(0.35±0.02 vs 0.27 ± 0.02)and Ⅲ(0.26 ± 0.02 vs 0.22 ± 0.03)in fetal carotid compared to normoxic control.Maternal hypoxia resulted in an increase in total collagen content of the carotid in the hypoxic animals compared to normoxic animals,but there was no statistical difference between the two groups. Conclusion These results reveal that maternal hypoxia upregulates the expression of TGF-β
1,CTGF,CollⅠ and CollⅢ in fetal carotid arteries in rabbits.