Academic literature on the topic 'QP Physiology ; RG Gynecology and obstetrics'

Glucocorticoids have been implicated in many processes including successful embryo implantation, placentation, and the growth and development of the fetus. Glucocorticoid treatment has been advocated as a treatment to improve reproductive outcome for a number of reasons. Prednisolone treatment has been associated with improvement in clinical outcome in women with recurrent miscarriage and improvement in outcome of In Vitro Fertilisation. Steroids have been found to reduce the high levels of uterine natural killer cells which have been associated with recurrent miscarriage and recurrent implantation failure. Glucocorticoids stimulate peri-implantation human chorionic gonadotrophin secretion from trophoblast of early human embryo and accelerate trophoblast growth and invasion. Elevated uterine NK cell levels during the implantation window are associated with reproductive failure and can be repressed by oral glucocorticoids. We have shown that decidualizing human endometrial stromal cells profoundly up regulate the expression and activity of 11beta-hydroxysteroid dehydrogenase type 1, the enzyme that converts inert cortisone to active cortisol; thus establishing a local cortisol gradient and activation of glucocorticoid and mineralocorticoid receptors. We also found that elevated levels of uterine natural killer cells in the stroma underlying the surface epithelium of endometrium are associated with defective decidualization of resident stromal cells, inadequate cortisol biosynthesis and suboptimal induction of corticosteroid-dependent enzymes involved in lipid droplet accumulation and retinoid transport pathway. Thus, impaired decidualization limits the induction of a local cortisol gradient in the stroma underlying the surface epithelium. This in turn accounts for possible inappropriate recruitment of uterine natural killer cells and suboptimal expression of metabolic genes involved in lipid biosynthesis and retinoid storage pathway. Based on the findings, we postulate that patients suffering recurrent miscarriage associated with high uterine NK cell density may benefit from corticosteroid treatment in early pregnancy; although this assumption will need to be tested in a larger clinical trial.

Hypertensive disorders of pregnancy are an increasingly common disorder in modern society. The increasing prevalence of women with pre-eclampsia superimposed on a background of chronic hypertension is a significant burden in modern society and is profoundly detrimental to both mother and child; during pregnancy and beyond. Little is understood about the development of these multifactorial hypertensive disorders, however there is increasing evidence that the manifestation of hypertensive disorders during pregnancy is not solely due to placental-derived dysfunctions and has important maternally-driven components. The stroke-prone spontaneously hypertensive (SHRSP) rat is a well-established model of human essential hypertension. SHRSP dams remain hypertensive throughout pregnancy and demonstrate an abnormal uterine artery structure and function at term. This project aimed to more fully characterise pregnancy in the SHRSP rat. The objectives were to assess maternal responses and determine how maternal hypertension impacts maternal and fetal well-being as well as placental development; to investigate the underlying genetic mechanisms behind the eventual abnormal pregnancy-dependent uterine artery remodelling; and, finally, to increase the maternal cardiovascular load in SHRSP pregnancy to establish a model of superimposed pre-eclampsia. In vivo and ex vivo techniques were used to characterise cardiovascular function in the hypertensive SHRSP and normotensive WKY rats during gestation, as well as assess pregnancy outcomes. The SHRSP dams were found to have similar cardiac function compared to WKY, yet there was evidence of impaired systemic vascular structure and function in late gestation and placental abnormalities. Nevertheless, the SHRSP maintained similar litter sizes to WKY and did not demonstrate any major impact on fetal growth. Further similarities between SHRSP and WKY pregnancy were revealed with the assessment of uterine artery function in early gestation. However, using RNA sequencing to elucidate the transcriptomic profiles of the uterine arteries, SHRSP were found to have strikingly different responses to pregnancy at the transcript expression level, compared to WKY. Finally, a model of superimposed pre-eclampsia was established by increasing the cardiovascular stress in the dam using angiotensin II infusion during pregnancy in SHRSP. This model had a significantly higher systolic and diastolic blood pressure than the already hypertensive SHRSP. The pregnancy-dependent increase in cardiac output, observed in SHRSP, was negated by AngII infusion and was reduced in the highest treatment group. These major cardiovascular impairments were observed alongside increased proteinuria and reduced fetal growth; all phenotypes found in severely pre-eclamptic women. This work has provided information on systemic and uterine specific vascular responses to pregnancy in SHRSP and WKY rats alongside detail of underlying transcriptional differences. This study was the first to examine uterine artery gene expression changes during pregnancy. The different transcriptomic profiles of early pregnancy changes in the two strains make this an intriguing model to study maternal-driven vascular remodelling in hypertensive pregnancy. Furthermore, this work demonstrated that increasing the cardiovascular load during pregnancy in SHRSP successfully mimics superimposed pre-eclamptic phenotypes and could be used in the assessment of novel therapeutic strategies. To conclude, the SHRSP has the potential to aid our understanding of human pre-eclamptic conditions, especially when endeavouring to determine the impact of maternally-driven components of hypertensive disorders of pregnancy.