The role of heat shock protein 20 and paraoxonase 2 in the human placenta: influence of obesity and labour

RG Gynecology and obstetrics

Abubaker, Fathia ; Lyall, Fiona

University:University of Glasgow

Department:School of Medicine, Dentistry & Nursing

关键词: HSP20, PON2, maternal obesity, labour;   

Others  :  http://theses.gla.ac.uk/6697/7/2015AbubakerMRes.pdf

来源: University of Glasgow

【 摘 要 】

The mechanisms that control uterine contractions duringparturition are better understood, however significant gaps in ourknowledge still remain. Until it is fully understood, it will bedifficult to understand the causes of idiopathic pre-term labour.The placenta plays an essential role during labour, which involvesinflammatory pathways, mechanical stretching, hormonal, and theneurological process. Placental oxidative stress is a feature ofhuman labour and maternal obesity. Heat-shock proteins (HSPs)can protect cells during stress. The small heat-shock protein 20(HSP20), which belongs to the sHSP family, acts as a chaperone aswell as regulating acting cytoskeleton dynamics, and may alsoregulate contractile protein activation. HSP20 is also known asHSPB6, and has been shown to protect against a number ofpathophysiological processes, including apoptosis and oxidativestress. The hypothesis of this work is that placental expression ofHSP20 would be changed during labour and obesity. In addition,expression may alter in different zones of the placenta. Werecruited 6 women in labour who delivered vaginally(uncomplicated labour), and 6 women who were delivered byCaesarean section (not in labour). Furthermore, women who hadnormal pregnancies with different body mass indices (BMI)s werealso recruited. Four BMI groups were studied: 1) BMI <30 (n=6), 2) BMI 30- 35 (n=6), 3) BMI 35-40 (n=6) and 4) BMI<40 (n=6).These women delivered by Caesarean section and were not inlabour. Sampling of 4 equally spaced pieces performed for 3placental zones (inner, middle and outer) of each placenta (total 12samples per placenta). Western blot analysis and RT-PCR wereused to investigate expression of HSP20. The results demonstratedthat there was a significant decrease in HSPB6mRNA expressionat the middle area in the labour group when compared to the nonlabourgroup (p=0.01). No significant difference was found at theinner and outer areas (p=0.3) for both. For BMI groups nodifferences were found in HSP20 expression at protein andmolecular levels.Oxidative stress and inflammation are significant features ofmaternal obesity, and Paroxonase 2 (PON2) has a clear role inoxidative stress and inflammation. It protects cells againstoxidative damage and lipid peroxidation, modulation ofendoplasmic reticulum stress, and regulation of apoptosis. As aresult, the hypothesis was that expression of placental PON2 wouldchange during obesity. PON2 was examined in placentas obtainedfrom women who had normal pregnancies with different BMIs.Four BMI groups were studied as per the HSP20 study. Westernblotting and real time PCR were performed to investigate theexpression of placental PON2, which has 2 isoforms: one at62kDa, and another at 43kDa, in all samples. The results showedno spatial differences in PON2 protein or mRNA expression of either isoform at the three sites (inner, middle, and outer) betweenall BMI groups.Conclusion: This is the first study to investigate the expression ofHSP20 in labour and during maternal obesity. Whether differencesin phosphorylation of the protein occur requires futureinvestigation. Similarly, this work is the first to investigate theexpression of PON2 in different BMI groups in the human placentaat the three sites (inner, middle, and outer). However, knowledgeconcerning its role in the reproductive system is still underinvestigation, and more studies need to be conducted to explain itsprecise roles. It would be of interest in future work to determinehow other PONs 1 and 2 are altered.