Use this URL to cite or link to this record in EThOS:
Title: Placenta sensing of, and responses to, the maternal environment
Author: Mosquera Escudero, Mildrey
ISNI:       0000 0004 6348 9149
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2016
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
The placenta's ability to sense the maternal environment may be necessary for adapting placental function to meet the needs of the growing fetus. The broader aim of this study was to identify mechanisms that could be involved in sensing which may act in addition to, or in conjunction with, established mechanisms such as the mTOR pathway. This was explored in two systems, a mouse model of maternal high-fat diet and metformin treatment and placentas from human cohorts. In the mouse model of maternal high-fat diet and metformin treatment, the two conditions were shown to have distinct effects on the placenta, indicating that they were acting via independent sensing pathways. RNA sequencing data demonstrated that maternal metformin treatment affected metabolic and transport pathways in the mouse placenta. To explore whether the effects of maternal metformin treatment on the placenta were direct, or mediated via effects on the mother, an in vitro model of metformin exposure was developed. Effects of metformin in vitro showed marked differences from those observed in vitro raining question about whether the effects observed in vitro were direct. Expression of the fat mass and obesity associated (FTO) gene was shown to be related to birth weight in placentas from the Southampton Women's Survey, but FTO expression was not altered in SGA babies compared to controls. To investigate whether FTO acted via regulation of microRNA, knock down experiments were performed followed by microRNA sequencing. Placental adaptation to the maternal environment is a complex process that is mediated by different sensing pathways in the placenta. Future studies need to distinguish between direct and indirect effects on the placenta and to focus on specific pathways via which signals may be mediated.
Supervisor: Lewis, Rohan ; Cleal, Jane ; Hanson, Mark Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available