Feto-placental vascular structure and function: comparison of within and between species variations

This thesis focuses on the structure and function of fetal circulation within the placenta, using imaging data to develop a data-to-model pipeline for understanding differences in human and rodent fetoplacental vascularisation. This thesis is motivated by a need to understand species differences, as despite promising therapies for pregnancy complications in animal models, clinical effectiveness is limited due to differences in placental structure and function between species. The first aim was to quantify the vascular branching patterns within a human placental cotyledon. Micro-computerised tomography (Micro-CT) imaging protocols were developed, allowing imaging at 5µm pixel resolution and extraction of vasculature down to vessels of approximately 45µm diameter. Branching analysis showed that the structural architecture of the cotyledons varies even within the same placenta, with the greatest asymmetry exhibited in the largest blood vessels. The second aim is to estimate the vascular resistance of the cotyledon based on the micro-CT data via a computational model predicting total vascular resistance as a function of structural characteristics. The model showed that vessel size contributed most to vascular resistance at each level within the vascular tree. Despite wide variation in vascular structure between cotyledons, there are similar characteristics of flow rate in smaller resistance vessels, suggesting a balance between vascular resistance and providing a large surface area for exchange. Finally, the pipeline was applied to rodent data to determine differences between rodents and human cotyledon feto-placental vasculatures. The analysis revealed structural differences between mice and humans, with rats showing more similarities to humans. Cross-species comparison of vascular resistance showed distinct differences between mice and rats, with the human cotyledon sitting between the two rodent species suggests similar resistance characteristics between humans and rodents, driven by differing mechanisms. In conclusion, this thesis provides tools for consistent investigation of comparative anatomy between species, demonstrated on rat, mouse, and human data, and combined with the prediction of vascular resistance derived from imaging. Future expansion of this pipeline could investigate pathological placentas in animal models, potentially improving disease models and therapies through a greater understanding of placental differences between species.

Name thesis:degree_name

PhD

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Bioengineering

Grantor dc:publisher

ResearchSpace@Auckland

Year dc:date.issued

2023

Author dc:creator

• Srinivasan, Vijayalakshmi

Advisors dc:contributor.advisor

• Clark, Alys
• James, Jo
• Oyston, Charlotte

Statement dc:rights

• Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Licence dc:rights.uri

• https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm

Handle dc:identifier.uri

https://hdl.handle.net/2292/70732

OAI identifier oai:identifier

oai:researchspace.auckland.ac.nz:2292/70732