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

Abubaker, Fathia (2015) The role of heat shock protein 20 and paraoxonase 2 in the human placenta: influence of obesity and labour. MRes thesis, University of Glasgow.

Abstract

The mechanisms that control uterine contractions during
parturition are better understood, however significant gaps in our
knowledge still remain. Until it is fully understood, it will be
difficult to understand the causes of idiopathic pre-term labour.
The placenta plays an essential role during labour, which involves
inflammatory pathways, mechanical stretching, hormonal, and the
neurological process. Placental oxidative stress is a feature of
human 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 as
well as regulating acting cytoskeleton dynamics, and may also
regulate contractile protein activation. HSP20 is also known as
HSPB6, and has been shown to protect against a number of
pathophysiological processes, including apoptosis and oxidative
stress. The hypothesis of this work is that placental expression of
HSP20 would be changed during labour and obesity. In addition,
expression may alter in different zones of the placenta. We
recruited 6 women in labour who delivered vaginally
(uncomplicated labour), and 6 women who were delivered by
Caesarean section (not in labour). Furthermore, women who had
normal pregnancies with different body mass indices (BMI)s were
also 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 in
labour. Sampling of 4 equally spaced pieces performed for 3
placental zones (inner, middle and outer) of each placenta (total 12
samples per placenta). Western blot analysis and RT-PCR were
used to investigate expression of HSP20. The results demonstrated
that there was a significant decrease in HSPB6mRNA expression
at the middle area in the labour group when compared to the nonlabour
group (p=0.01). No significant difference was found at the
inner and outer areas (p=0.3) for both. For BMI groups no
differences were found in HSP20 expression at protein and
molecular levels.
Oxidative stress and inflammation are significant features of
maternal obesity, and Paroxonase 2 (PON2) has a clear role in
oxidative stress and inflammation. It protects cells against
oxidative damage and lipid peroxidation, modulation of
endoplasmic reticulum stress, and regulation of apoptosis. As a
result, the hypothesis was that expression of placental PON2 would
change during obesity. PON2 was examined in placentas obtained
from women who had normal pregnancies with different BMIs.
Four BMI groups were studied as per the HSP20 study. Western
blotting and real time PCR were performed to investigate the
expression of placental PON2, which has 2 isoforms: one at
62kDa, and another at 43kDa, in all samples. The results showed
no spatial differences in PON2 protein or mRNA expression of either isoform at the three sites (inner, middle, and outer) between
all BMI groups.
Conclusion: This is the first study to investigate the expression of
HSP20 in labour and during maternal obesity. Whether differences
in phosphorylation of the protein occur requires future
investigation. Similarly, this work is the first to investigate the
expression of PON2 in different BMI groups in the human placenta
at the three sites (inner, middle, and outer). However, knowledge
concerning its role in the reproductive system is still under
investigation, and more studies need to be conducted to explain its
precise roles. It would be of interest in future work to determine
how other PONs 1 and 2 are altered.

• Item Type: Thesis (MRes)
• Qualification Level: Masters
• Keywords: HSP20, PON2, maternal obesity, labour
• Subjects: R Medicine > RG Gynecology and obstetrics
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Supervisor's Name: Lyall, Prof. Fiona
• Date of Award: 2015
• Depositing User: Mrs Marie Cairney
• Unique ID: glathesis:2015-6697
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 05 Oct 2015 15:47
• Last Modified: 06 Oct 2015 10:50
• URI: https://theses.gla.ac.uk/id/eprint/6697