Folliculogenesis is a complex process which describes the maturation of the ovarian follicle, from the primordial stage all the way to the ovulation of the antral follicle, and its sequela, the formation of the corpus luteum (CL). Imitation switch (ISWI) proteins are a class of ATP-dependent chromatin remodelers which mobilize nucleosomes to regulate a number of cellular processes including transcription, replication, and DNA repair. The pattern of expression of the mammalian ISWI proteins SNF2H and SNF2L in the mouse ovary suggests a role in the coordination of the proliferation and differentiation of granulosa cells during folliculogenesis. Here, we report that SNF2H is associated with proliferating granulosa cells, while SNF2L expression is induced following the LH surge which triggers their terminal differentiation into luteal cells. Knockdown of Snf2l by siRNA is sufficient to downregulate the expression of StAR, an important steroidogenic enzyme, and marker of the CL. Furthermore, SNF2L is thought to directly regulate StAR expression by physically binding to its promoter as indicated by chromatin immunoprecipitation (ChIP). In order to identify additional targets regulated by SNF2L, an unbiased microarray screen was developed to look for genes induced by LH in a SNF2L-dependent manner. One of the candidates, Fgl2 is strongly induced at 8h post hCG only in granulosa cells with intact SNF2L activity. Furthermore overexpression of SNF2L is sufficient to induce FGL2, and SNF2L is present on its promoter in the SIGC rat granulosa cell line. Some of the SNF2L binding partners that may be important in this regulation are PR-A and FLI-I, which have been found to interact with SNF2L by IP. Finally we describe here the phenotype of a Snf2l KO mouse which includes multiple reproductive defects, including resistance to superovulation, low secondary follicle counts, and a high incidence of abnormal antral follicles. Taken together these data suggest an important role of ISWI proteins in folliculogenesis, particularly SNF2L, which may regulate multiple genes important for the terminal differentiation of granulosa cells into luteal cells following the LH surge.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2009. / Härtill 4 uppsatser.

Thesis (M. Sc.)--University of Hong Kong, 1972. / Typewritten.

No description available.

<p> Environmental pollutants can act as endocrine disruptors to affect the biology of organisms including, development, reproduction, behavior, and overall health. Many endocrine disrupting chemicals (EDCs) can mimic or inhibit functions of sex steroids which are critical for the development and maintenance of vertebrate reproductive systems. Sex steroids also interact with arginine vasotocin (AVT)/arginine vasopressin (AVP; mammalian homologue) systems to mediate vertebrate social and sexual behaviors, including vocalizations in male anurans. I used the Western clawed frog, <i>Xenopus tropicalis, </i> as an amphibian model species to evaluate the effects of exposure to EDCs on AVT-regulated behaviors and on brain AVT and sex steroid signaling systems. </p><p> In order to understand the role of neurohormones and social stimuli in behavior of <i>X. tropicalis,</i> I studied the effect AVT and human chorionic gonadotropin (hCG) administration and the influence of different social contexts on sexual behaviors, including calling, in males. I found that AVT and hCG treatment alone and in combination induces male sexual behavior, and the presence of a female is necessary to stimulate this behavior. I also analyzed the expression of genes related to AVT and sex steroid signaling in the brain of male and female <i>X. tropicalis</i> to identify genes that are expressed sexually dimorphically and could be potentially altered by EDC exposure. </p><p> Then I utilized the behavior and gene expression assays I developed to study the effects of developmental exposure to the synthetic androgen 17&beta;-trenbolone (17&beta;-TB) on behavior, fecundity, morphology, and brain gene expression in adult <i>X. tropicalis.</i> Developmental 17&beta;-TB exposure reduced sexual behavior and inhibited female egg release during breeding trials. Exposure to 17&beta;-TB also blocked oviduct development and altered AVT-related brain gene expression in females. </p><p> In another study I evaluated the effects of adult exposure to the common EDCs bisphenol A (BPA), nonylphenol (NP), and triclosan (TCS) or a mixture of the three on sexual behavior, morphology, and brain gene expression in adult male <i>Xenopus tropicalis.</i> Behavior and brain gene expression were not significantly affected, but TCS-exposed animals had a lower normalized liver weight than animals exposed to BPA or the chemical mixture. Males exposed to BPA, NP, and the mixture also exhibited increased oviduct development compared to TCS-exposed males, and the source of the animals influenced oviduct development. </p><p> Results from my dissertation research demonstrate that exposure to endocrine disruptors can affect multiple levels of physiology. Gender, timing of exposure and nature of the chemical are also critical factors in determining these physiological effects. Importantly, because there is evolutionary conservation in vertebrates for the role of sex hormones in regulating the reproductive system as well as the AVT/AVP system and related social behaviors, my work has important broader implications for endocrine-disrupting effects from environmental chemical exposure for all wildlife and humans.</p>

Folliculogenesis is a complex process which describes the maturation of the ovarian follicle, from the primordial stage all the way to the ovulation of the antral follicle, and its sequela, the formation of the corpus luteum (CL). Imitation switch (ISWI) proteins are a class of ATP-dependent chromatin remodelers which mobilize nucleosomes to regulate a number of cellular processes including transcription, replication, and DNA repair. The pattern of expression of the mammalian ISWI proteins SNF2H and SNF2L in the mouse ovary suggests a role in the coordination of the proliferation and differentiation of granulosa cells during folliculogenesis. Here, we report that SNF2H is associated with proliferating granulosa cells, while SNF2L expression is induced following the LH surge which triggers their terminal differentiation into luteal cells. Knockdown of Snf2l by siRNA is sufficient to downregulate the expression of StAR, an important steroidogenic enzyme, and marker of the CL. Furthermore, SNF2L is thought to directly regulate StAR expression by physically binding to its promoter as indicated by chromatin immunoprecipitation (ChIP). In order to identify additional targets regulated by SNF2L, an unbiased microarray screen was developed to look for genes induced by LH in a SNF2L-dependent manner. One of the candidates, Fgl2 is strongly induced at 8h post hCG only in granulosa cells with intact SNF2L activity. Furthermore overexpression of SNF2L is sufficient to induce FGL2, and SNF2L is present on its promoter in the SIGC rat granulosa cell line. Some of the SNF2L binding partners that may be important in this regulation are PR-A and FLI-I, which have been found to interact with SNF2L by IP. Finally we describe here the phenotype of a Snf2l KO mouse which includes multiple reproductive defects, including resistance to superovulation, low secondary follicle counts, and a high incidence of abnormal antral follicles. Taken together these data suggest an important role of ISWI proteins in folliculogenesis, particularly SNF2L, which may regulate multiple genes important for the terminal differentiation of granulosa cells into luteal cells following the LH surge.

Thesis (Ph. D.)--University of Adelaide, 1986. / Typescript. Copies of two published papers by the author, in back. Includes bibliographical references (leaves 111-133).

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2006. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Texas at Austin, 2003. / Supervisor: Mary Ann Rankin. Vita. Includes bibliographical references. Also available from UMI.

<p>This study aimed to characterize the impact of treatment infrastructure upgrades on the occurrence of endocrine disrupting chemicals (EDCs) discharged by a wastewater treatment plant (WWTP) effluent and their subsequent effects on fish endocrine function. This site has been evaluated before and after two major upgrades in wastewater treatment infrastructure, which were implemented in 2007 and 2012. Our study assessed the potential impacts on the Boulder Creek receiving water, as well as identified and evaluated the extent of estrogenic endocrine disruption in the native fathead minnow (Pimephales promelas) that may be occurring after the implementation of the 2012 upgrade. We conducted an integrative, 8-week, on-site, continuous-flow, exposure experiment using adult male fathead minnows to assess in vivo estrogenicity of the WWTP effluent water, relative to reference water and results from prior years (both pre- and post-upgrade). We collected data for a wide array of biological endpoints. Results for plasma vitellogenin concentrations and sperm development were emphasized. It was found that in vivo effluent estrogenicity following the 2012 upgrade was insignificant in comparison to pre-upgrade levels. However, the occurrence of an extreme flood event in the Boulder area resulted in the detection of some significant effluent estrogenicity, indicating that such conditions may impact the ability of WWTPs to effectively remove estrogenic EDCs from the effluent.