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This research responded to the need to define evidence-based criteria of maternal risk by developing a model - the Pre-eclampsia Integrated Estimate of RiSk (or PIERS) model ? that predicts a combined adverse maternal outcome (mortality and/or significant morbidities) within 48 hour of, and up to s…
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Pre-eclampsia, which is characterized by maternal hypertension, proteinuria, hypoperfusion of end organs and a systemic maternal innate inflammatory response, is a leading cause of maternal mortality and morbidity world-wide. When of early-onset, pre-eclampsia is associated with fetal intrauterine …
Pre-eclampsia (PET) continues to contribute to maternal and perinatal morbidity and mortality. Management decisions include an evaluation of maternal risk, which is assisted by expert opinion-based guidelines, while not accounting for gestational age (GA) at diagnosis. We evaluated the feasibility …
Nuclear receptors including estrogen receptors (ERs) and progesterone receptors (PRs) are activated by their ligands as well as by signaling pathways in response to peptide hormones and growth factors. In gonadotrophs, gonadotropin releasing hormones (GnRHs) act via the GnRH receptor (GnRHR). Both …
The distintegrin-like and metalloproteinase with thrombospondin repeats (ADAMTS) are members of a gene family of secreted, multidomain and multifunctional proteinases that are able to proteolytically degrade a diverse array of cellular, extracellular and extracellular matrix (ECM) substrates. We ex…
Ovarian cancer is the most lethal gynecological cancer in the Western world, but comparatively little is known about its development. Epithelial ovarian carcinomas are thought to originate in the ovarian surface epithelium (OSE), i.e. the mesothelium covering the ovary, but experimental evidence fo…
The gonadotropin - releasing hormone (GnRH) receptor is a plasma membrane associated receptor and a member of the GTP - binding protein coupled receptor family. The interaction of the ligand, GnRH, and the GnRH receptor is a critical event in the endocrine control of reproduction. This coupling sti…
This thesis investigated the expression and regulation of cytochrome P450s, aromatase (P450arom) and cholesterol side chain cleavage (P450scc) enzyme mRNAs in human granulosa-luteal cells using reverse transcription-polymerase chain reaction (RT-PCR). The two enzymes are instrumental in steroid hor…
There is increasing evidence to suggest that activin can function as an autocrine/paracrine regulator in various tissues, including the reproductive system. At the cellular level, activin acts via a family of activin receptor (ActR) subtypes which includes two type I (ActRI and ActRLB) and two type…
It is increasingly apparent that GnRH-II acts as an autocrine/paracrine regulator in non-pituitary tissues, in addition to its role in the regulation of gonadotropin synthesis, and is an important player in cancer cell biology. High levels of GnRH-II and GnRHR in malignant ovarian tumors as compare…
These studies examined the effects of prostaglandin-F[sub 2a] (PGF[sub 2a]) on progesterone and 178-estradiol (estradiol) production, as well as DNA and PGF[sub 2a]-receptor (PGF[sub 2a]-R) mRNA levels, in the human granulosa-luteal cell (GLC). Additionally, the interactions of PGF[sub 2a] with hum…
It is well established that LH action is mediated primarily by adenylate cyclase/cAMP. Conversely, the role of inositol phosphate/calcium in LH signalling has only recently been investigated. We examined the effects of gonadotrophins on intracellular calcium mobilisation in HEK293 cells transiently…
Light microscopy has remained the primary tool for the assessment of embryo quality and the selection of embryos for transfer in clinical IVF practice. Recent studies have suggested that metabolomic profiling of embryo culture media can distinguish human embryos with better implantation potential. …
Activin A (homodimer of inhibin βA-subunit) is known to increase inhibin βB-subunit and inhibin B (heterodimer of inhibin α- and βB-subunit) levels and decrease progesterone accumulation in human granulosa cells. Growth differentiation factor 9 (GDF9) is a potent paracrine regul…
Disruptions or imbalances of the vaginal microbiome can lead to negative reproductive health consequences for women, including an increased risk of sexually transmitted infections, pelvic inflammatory disease, and preterm birth. HIV-positive women may be particularly vulnerable to microbiome disrup…
Human newborns exposed in utero to maternally administered SSRIs such as fluoxetine (FX) have an increased risk of adverse pregnancy outcomes including poor neonatal adaptation. This comprises respiratory difficulty, jitteriness, cyanosis when feeding and persists for several days after birth. Seve…
Aberrant epidermal growth factor receptor (EGFR) activity contributes to the development of epithelial ovarian cancer (EOC), a common and lethal female malignancy. Elucidating the regulation of EGFR function will improve treatments for EOC and the survival of patients. This study aims to elucidate …
Pregnancies derived from in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are associated with increased rates of chromosome abnormalities, congenital malformations, low birth weight, pre-term births, multiple gestations, and imprinting disorders. Assisted reproductive techno…
With the increasing use of assisted reproductive techniques (ART) every year, concerns have been raised regarding the possible effect these procedures have on the health of the children procured by them. Although patients born via ART are usually healthy, studies have associated these procedures wi…
Sex hormone-binding globulin (SHBG) binds androgens and estrogens with high affinity, and regulates the distribution of these sex steroids in the blood and other biological fluids. Liver is the primary site of SHBG production, but the human SHBG transcription unit responsible for this is also expre…