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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…
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…
In the present study, the effects of clomiphene citrate (CC) on ovulation, ovarian growth and ovarian steroidogenesis were examined. Ovulation in rats in response to PMSG was completely blocked by administration of three daily treatments of 1.0 mg CC/rat, but was restored by administration of hCG a…
Ritodrine is a beta-adrenergic agonist commonly used to inhibit premature labor contractions in women. The primary goal of ritodrine tocolysis is to prolong gestation, however, other indications may include fetal distress. The purpose of the current study was to examine the metabolic and behavioral…
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…
A delicate balance of steroid and gonadotrophic hormones is essential for intrafollicular oocyte maturation and successful fertilization and embryonic development. Previous studies have demonstrated that a superovulatory dose of pregnant mare serum gonadotrophin (PMSG) has excessive gonadotrophic a…
Due to the ?flare effect? associated with the flare protocol, variation in the degree of follicular maturation during stimulation may result in differences in follicle response as compared to the luteal protocol which is based on maximal pituitary suppression and synchronization of follicular matur…
Pre-eclampsia remains one of the most common causes of maternal mortality in the developed world, and we still have no known effective prophylaxis and proven modifiers. The recent successful clinical trial of recombinant human activated protein C (rhAPC) in the management of SIRS (systemic inflamma…
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…
Ovarian cancer is the sixth most common cancer and the fifth leading cause of cancer-related death among women in developed countries. There is increasing evidence suggesting that the hormonal environment of the normal ovarian surface epithelium (OSE) and ovarian epithelial cancer (OEC) cells is as…
Male carriers of chromosomal abnormalities (CA) are more frequent in the infertile population. These men have higher levels of sperm aneuploidy due to the aberrant segregation of the chromosomes involved in the abnormality. The presence of a CA may also influence the segregation of other chromosome…
Intracytoplasmic sperm injection (ICSI) has been a successful assisted reproductive technique for men with severe male-factor infertility. However, ICSI requires the subjective selection of normal looking sperm, which does not preclude the transmission of genetically abnormal sperm. Correlation bet…
While the introduction of intracytoplasmic sperm injection (ICSI) has revolutionized the treatment of male infertility, concerns have been raised regarding the risk of chromosomal abnormalities in pregnancies derived from ICSI. Studies on sperm from infertile men have suggested that this population…
In contrast to the success of ICSI in treating male infertility, concerns have been raised about the health outcomes of the children conceived through this procedure. Cohort studies have shown that the ICSI population has an increase in low birth weight (LBW), birth defects, chromosomal abnormaliti…
Homeobox genes, which code for families of transcription factors, act at the top of genetic hierarchies. HOX genes specify positional identity during development, and in adult tissues, regulate differentiation and proliferation. Most ovarian carcinomas are derived from the ovarian surface epitheliu…
Loss of BRCA1/BRCA2 function through genetic or epigenetic mechanisms is common in epithelial ovarian carcinomas (EOC), but because there are multiple potential mechanisms of loss, the overall frequency is unknown. We characterized loss of BRCA1/BRCA2 at the DNA, RNA and protein level from an unsel…
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 …
n approximately 40% of ovarian cancers, PIK3CA, which encodes the p110α catalytic subunit of phosphatidylinositol 3-kinase (PI3K) is amplified. This amplification correlates with increased PIK3CA transcription, p110α protein expression, and PI3K activity. Moreover, PIK3CA is implicated as…
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 …