Cross, James C.Hallgrímsson, BenediktEaton, Malcolm Ellis2020-06-122020-06-122020-06-08Eaton, M. E. (2020). Adaptability and Function of the Placental Endocrine System (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.http://hdl.handle.net/1880/112165The placenta acts as the arbitrator for the exchange of nutrients and gases across the feto-maternal interface, ensuring that the fetus can grow, and the mother can remain healthy to deliver and nurture her offspring. The placenta achieves this by changing its structure and function throughout gestation. Failure to undergo these changes is a major cause of obstetric syndromes, intrauterine growth restriction and pre-term birth. These complications result in deleterious long-term outcomes for both fetus and mother and understanding the complex aetiology of these complications is fundamental to impacting lifelong health. One of the less well-studied ways that the placenta adapts is by secreting hormones that regulate maternal adaptations to pregnancy. Previous work in the Cross lab established that a family of 22 Prolactin-related hormone genes, termed the placenta Prolactin-related hormones (PPRH), that are specifically expressed from the mouse placenta regulate maternal adaptations to pregnancy. The mouse provided a model to study how the placenta adapted its structure and function to changes in the maternal environmental and PPRH levels. We first established the normal course of cell growth in the placenta to understand the timing of changes in trophoblast cells number and found evidence of cell hypertrophy and endoreduplication in addition to hyperplasia. We then challenged pregnancies with a maternal diet low in protein. We found that the normal course of cellular differentiation and growth was altered, but that these changes were adapting to preserve fetal growth. Interestingly, we found that male and female fetuses used different strategies. We then created a model that was haplo-deficient in PPRH genes and, to our surprise, fetuses were overgrown while mothers failed to gain weight late-term. Interpreting the expression patterns of individual hormone genes in the context of other placental knockouts helped us identify putative roles for several hormones and demonstrated that this locus is highly adaptable. Distinguishing the targets and functions of these hormones and separating between primary and secondary effects remains a topic of interest. In examining PPRH null mutants, we found that the size of the maternal liver, spleen and gut were altered, along with the gut microbiota. These results indicate that the placenta is a highly adaptable organ that changes in normal pregnancy and has mechanisms built in to mitigate impacts of environmental changes. By studying the changes over time, we reveal insights into how placenta-specific hormones regulate maternal physiology, placental function and fetal growth outcomes. There is still a great deal to learn about the placenta but increasing our understanding of this fascinating organ will contribute to the interpretation and treatment of obstetric syndromes.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.Placenta, Endocrinology, Hormones, Pregnancy physiology, Embryonic development, MicrobiotaBiology--MolecularPhysiologyObstetrics and Gynecologydoctoral thesis10.11575/PRISM/37906