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Title: Kisspeptin : a novel regulator of human foetal adrenocortical development and function
Author: Harshini, Katugampola
ISNI:       0000 0004 7653 8405
Awarding Body: Queen Mary University of London
Current Institution: Queen Mary, University of London
Date of Award: 2018
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Context: The human foetal adrenal (HFA) is an integral component of the foeto-placental unit and important for the maintenance of pregnancy. Low kisspeptin levels during pregnancy are associated with miscarriage, and kisspeptin and its receptor are expressed in the HFA. However, the role of kisspeptin in foetal adrenal function remains unknown. Objective: The objective of this work was to determine the role of kisspeptin signaling in the developing HFA. Methods: Experiments using H295R adrenocortical cells and primary HFA cells as in vitro models of the foetal adrenal were conducted. The spatiotemporal expression of the kisspeptin receptor, Kiss1R in the HFA was examined. The production of dehydroepiandrosterone sulphate (DHEAS) from HFA cells after kisspeptin treatment, alone or in combination with adrenocorticotropic hormone or corticotropin-releasing hormone was compared. The association of plasma kisspeptin levels with HFA size was analysed in a longitudinal clinical study. Thirty-three healthy pregnant women were recruited at their 12-week routine antenatal ultrasound scan. Serial measurements of foetal adrenal volume (FAV) and maternal kisspeptin levels at four antenatal visits (∼20, 28, 34, and 38 weeks' gestation) were collected. Outcomes of pregnancy were recorded, including neonatal auxology and complications in the postnatal period. Neoantal adrenal remodeling was characterized by Results: Expression of Kiss1R was present in the HFA from 8 weeks after conception to term and was shown in the inner foetal zone. Kisspeptin significantly increased DHEAS production in H295R and second-trimester HFA cells. Serial measurements of kisspeptin confirmed a correlation with FAV growth in the second trimester, independent of sex or estimated foetal weight. Conclusions: Together, these studies demonstrate that kisspeptin plays a key role in the regulation of the HFA, and thus the foeto-placental unit, particularly in the second trimester of pregnancy.
Supervisor: Not available Sponsor: MRC ; Wellcome Trust ; British Society of Paediatric Endocrinology (BSPED) ; Rosetrees Charity
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Kisspeptin ; foetal adrenocortical development ; Endocrinology