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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…
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…
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 …
The association between subsets of male infertility, oligoasthenoteratozoospermia (OAT), obstructive azoospermic (OA), non-obstructive azoospermia (NOA), and increased risk of having chromosomal abnormalities in the sperm has not been investigated. Chromosomal aneuploidy in sperm will be systematic…
Preeclampsia is a pregnancy-specific condition, and it still remains one of the most common causes of maternal mortality in the developed world. Although the exact cause of preeclampsia has not been identified, it is most widely accepted that preeclampsia results from incomplete placentation. Inter…
Remodeling of the endometrial extracellular matrix, which occurs during the early stages of pregnancy in the human, is mediated by the temporal expression of urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMP) in both the maternal and fetal compartments and counterbalance…
The common epithelial ovarian tumors appear to arise from the ovarian surface epithelium (OSE), which is a simple squamous-to-cuboidal meso^helium covering the ovary. The exact mechanism of ovarian tumorigenesis is not well known even though this disease is the most frequent cause of cancer death i…
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…
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…
The studies undertaken herewithin sought to characterize the pattern of regulation of the gonadotrophin-releasing hormone receptor (GnRH-R) mRNA levels in the rat ovary. The demonstration of gonadotrophin-releasing hormone (GnRH) transcripts in steroidproducing and steroid-dependent tissues suggest…
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 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…
Superovulation causes detrimental effects, including embryonic loss and implantation failure. This study determined potential roles for insulin-like growth factor (IGF-I) in uterine environment regulation and preimplantation development, in conjunction with the detrimental effects of superovulation…
The placenta is an important endocrine organ producing large amounts of steroid and protein hormones which are released into the maternal and fetal circulations. Moreover, it has a very high metabolic rate and consumes a significant proportion of the oxygen and glucose delivered to the uterus and i…
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…
In vitro fertilization (IVF) has been achieved in several mammalian species, including humans. Using the technique of IVF and embryo transfer, pregnancies can now be established in infertile women and thousands of live births have occurred. However, many of the embryos transferred to the uterus fai…
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…
In order to characterize and compare the pattern of inhibin production in the follicular phase between patients of the clomiphene citrate/human menopausal gonadotropin (hMG) and Buserelin/hMG protocols in in-vitro fertilization, serum inhibin levels from 20 patients in each protocol were measured. …