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Teaser, summary, work performed and final results

Periodic Reporting for period 1 - PlaEndo (The Remote Control of Maternal Metabolism by the Placenta)

Teaser

Pregnancy is characterised by profound changes in maternal physiology. For instance, there are changes in the metabolic, cardiovascular, immune and renal systems of the mother which enable her to support fetal nutrient supply and growth. These changes are signalled in part by...

Summary

Pregnancy is characterised by profound changes in maternal physiology. For instance, there are changes in the metabolic, cardiovascular, immune and renal systems of the mother which enable her to support fetal nutrient supply and growth. These changes are signalled in part by the production of protein hormones by the placenta (Napso et al., 2018). Failures in maternal adaptation and placental function lead to pregnancy complications such as abnormal birth weight and gestational diabetes which have immediate and lifelong health consequences for mother and child. However, we lack information on the identity of hormones secreted by the placenta that mediate the changes in maternal physiology.
This study aimed to unbiasedly characterise the secretory output of cultured placental cells and there impact on maternal physiology and fetal development.

Work performed

Methods: The mouse was used in this study as the endocrine function of the placenta is performed by a discrete zone, the junctional zone (Jz). Primary cell cultures from the whole placenta (WP) and isolated Jz from dams on day 14 and 16 of gestation were established (term=20 days). Cell viability necrosis and apoptosis were measured over the 5 day culture using XTT and LDH release assays and Tunel, p53 and Bax expression. The expression of Jz cell marker genes was assessed by qPCR and proteins released into the conditioned media on day 2 of culture were identified by mass spectrometry and bioinformatic analyses. Data are from n=5-6.
Results: Cell culture characteristics were similar for those prepared from WP and Jz at both pregnancy days. Cell viability was reduced by 20% at 24h of culturing, with a corresponding increase in necrosis (but not apoptosis). At 48h-72h, cell viability increased by 200-500%, and necrosis levels reduced by 100%. At 96h-120h of culture, cell viability reduced in line with increased apoptosis. All three Jz cell types were present in all cultures at 24h to 96h. Conditioned media of day 16 WP cultures contained a total of 932 proteins in at least 4 out of 5 samples, of which 167 are also expressed reported expressed by human placenta. Gene ontology suggested these proteins are involved in activities such as metabolic regulation, immune modulation, signalling and growth. Mass spectrometry analysis revealed ~800 proteins secreted from the placenta of the mouse which share homologue to human proteins. These proteins were further analysed using bioinformatic tools for there involvement in know pregnancy conditions such as gestational diabetes and pre-eclampsia.
Conclusion: A map of the mouse placental secretome has been created using primary cell cultures. This map will be the first step in identifying new biomarkers for pregnancy comlications in humans and understanding these comlications mechanism and their impact on maternal physiology and feta development.

Final results

Future work will study the function of secreted proteins that are expressed by the human placenta to identify their role in the maternal support of fetal growth.

Website & more info

More info: https://www.pdn.cam.ac.uk/other-pages/sferruzzi-perri/amanda-sferruzzi-perri-lab-members.