Typescript (photocopy). / Digitized by Kansas Correctional Industries

Offprints of the author's articles inserted / Bibliography: leaves [122]-145 / vii, 147 leaves, [22] leaves of plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Biochemistry, 1985

The objective of this experiment was to determine whether norgestomet implant insertion following melengestrol acetate (MGA) administration altered LH pulse frequency and follicular dynamics. Multiparous Angus cows were randomly assigned to receive MGA (.5 mg*cow⁻¹*d⁻¹ ; MGA; n = 14) for 18 d or to receive MGA (.5 mg*cow·⁻¹ l*d⁻¹; MGA-N; n = 11) for 15 d and a norgestomet implant for 4 d beginning on d 15. Ultrasound was used to record images of each ovary in cows beginning on d 8 of MGA administration. On d 16, serial blood samples were collected from all cows in replicate one (MGA, n=6; MGA-N, n=6) for quantification ofLH pulse frequency. A persistent, dominant follicle was identified in all cows on d 8 ofMGA administration. Forty-three percent and 64% (P > .10) of MGA and MGA-N cows, respectively, initiated a new wave of follicular development during treatment that was the source of the ovulatory follicle. Pulse frequency of LH did not differ between MGA and MGA-N cows or between cows that ovulated a persistent (PERSIST) follicle and those that ovulated a follicle from a new follicular wave (NEW). Growth rate of the ovulatory follicle for the 7 d preceding ovulation was greater in PERSIST than in NEW cows (P < .01). Diameter of the owlatory follicle on the day preceding ovulation was greater in PERSIST cows than in NEW cows (P < .01). In conclusion, MGA administration caused a persistent follicle to develop, but that follicle was unable to be regressed consistently by supplemental norgestomet administration. / Master of Science

No / Chemotherapy has severe side effects in normal rapidly proliferating organs, such as hair follicles, and causes massive apoptosis in hair matrix keratinocytes followed by hair loss. To define the molecular signature of hair follicle response to chemotherapy, human scalp hair follicles cultured ex vivo were treated with doxorubicin (DXR), and global microarray analysis was performed 3 hours after treatment. Microarray data revealed changes in expression of 504 genes in DXR-treated hair follicles versus controls. Among these genes, upregulations of several tumor necrosis factor family of apoptotic receptors (FAS, TRAIL (tumor necrosis factor–related apoptosisinducing ligand) receptors 1/2), as well as of a large number of keratin-associated protein genes, were seen after DXR treatment. Hair follicle apoptosis induced by DXR was significantly inhibited by either TRAIL-neutralizing antibody or caspase-8 inhibitor, thus suggesting a previously unreported role for TRAIL receptor signaling in mediating DXR-induced hair loss. These data demonstrate that the early phase of the hair follicle response to DXR includes upregulation of apoptosis-associated markers, as well as substantial reorganization of the terminal differentiation programs in hair follicle keratinocytes. These data provide an important platform for further studies toward the design of effective approaches for the management of chemotherapy-induced hair loss.

No / Hair follicle development and its postnatal regeneration are characterized by dramatic changes in its microanatomy and cellular activity, which are controlled by multiple signalling pathways, transcription factors and epigenetic regulators, including microRNAs (miRNAs). miRNAs and their targets form remarkably diverse regulatory networks, playing a key role in the execution of gene expression programmes in the different cell lineages of the hair follicle. This review summarizes the roles of miRNAs in the control of hair follicle development, cycling and hair pigmentation, emphasizes the remaining problems/unanswered questions, and provides future directions in this rapidly growing and exciting area of research / MRC

No description available.

The primordial follicle pool is the main source of developing follicles in the ovary. The length of reproductive life and the onset of menopause are governed by the amount of primordial follicles in the ovary. The genetic factors and molecular mechanisms that maintain the primordial follicles in a dormant and surviving state for the whole of reproductive life are not well understood. The phosphatidylinositol 3 kinase (PI3K) signaling pathways in the oocyte that control oocyte growth and early follicular development are largely unknown. The major aim of this thesis was to investigate the functional role of the intra-oocyte PI3K pathway in the regulation of primordial follicle activation and survival.  Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a major negative regulator of PI3K. The conditional deletion of Pten in the oocytes of primordial follicles led to the overgrowth of oocytes and activation of the entire pool of primordial follicles. There were higher numbers of activated primordial follicles at postnatal day 8 (PD8) in ovaries lacking PTEN in oocytes; by PD35 all the primordial follicles were activated and all the follicles were depleted by 12 weeks, causing premature ovarian failure (POF). In addition, the rate of follicular death that occurs during sexual maturity is reduced in ovaries that lack PTEN in oocytes. Further mechanistic studies revealed that loss of Pten in oocytes resulted in elevated Akt signaling and upregulation of both expression and activation of ribosomal protein S6 (rpS6). The overactivation of primordial follicles in ovaries that lack PTEN in oocytes is believed to be due to elevated expression and activation of rpS6. PTEN in oocytes is indispensable for the maintenance of primordial follicles in dormancy.  To study the role of the intra-oocyte PI3K signaling pathway in controlling the survival and maintenance of primordial follicles, 3-phosphoinositide-dependent protein kinase-1 (PDK1) was deleted in oocytes of primordial follicle. The loss of Pdk1 in oocytes led to the depletion of most primordial follicles around the onset of sexual maturity, causing POF during early adulthood. Furthermore, the activation of Akt, p70 S6 kinase 1 (S6K1), and rpS6 was impaired in oocytes that lacked PDK1. The suppressed PDK1–Akt–S6K1–rpS6 signaling in oocytes appears to be responsible for the loss of primordial follicles. The excessive activation of primordial follicles seen in the absence of Pten in oocytes could be reversed by concurrent deletion of Pdk1. In addition, the elevated activation of Akt and S6K1 in the absence of PTEN in oocytes was not observed in PTEN and PDK1 double mutant mice. Similarly, the hyperphosphorylation of rpS6 in oocytes that lack PTEN was prevented in double mutant mice, which was most likely due to downregulation of S6K1 activation. Thus, inactivation of rpS6 in double mutant mice might be the reason for the prevention of excessive primordial follicular activation and survival.  PTEN and PDK1 in oocytes are essential for the maintenance of quiescence and survival of primordial follicles. The molecular network involving PI3K/PTEN–PDK1 signaling in oocyte controls the survival, loss, and activation of primordial follicles, which together govern reproductive aging and determine the length of reproductive life in females. The results of the above studies indicate that the mammalian oocyte serves as the seat of programming of follicular activation and survival.

<p>The objective of this research was to assess ultrasound image attributes of human dominant ovarian follicles in the final stages of development during natural and oral contraceptive (OC) cycles, as well as characterize ovarian follicular and endometrial development during and after continuous versus conventional dosing schemes. We utilized sophisticated computer algorithms to elucidate an association between image attributes and physiologic status of follicles in their final stage of development. We used transvaginal ultrasonography to quantify changes in the numbers and diameters of ovarian follicles and changes in endometrial thickness and pattern during and following discontinuation of two different regimens of OC. Developmental changes in ovarian follicles and corpora lutea were correlated with serum estradiol-17â and progesterone, respectively to provide a comprehensive approach to examining ovarian and uterine function. </p><p>We reported for the first time that follicles which develop during natural and OC cycles have similar image attributes, which provides preliminary evidence that image attributes of human follicles are associated with physiologic status during the growth phase. Further research should be performed to elucidate the exact correlation between image attributes during all stages of follicular development throughout the menstrual cycle, prediction of dysfunctional follicular development (i.e., hemorrhagic anovulatory follicles) and the effects of different OC formulations on follicle development. Once the association between image attributes and various scenarios of follicular development are determined, a computer program could be developed to assess follicular health with a single ultrasound examination, obviating many ethical constraints that currently prevent large scale progress in ovarian follicular research. We further documented that continuous OC administration schemes provide greater follicular suppression than conventional dosing schemes. No dominant follicles developed during three consecutive 28 day cycles of continuous OC use, whereas eight dominant follicles developed during the same time period of conventional OC use. We interpreted these findings to mean that continuous OC dosing schemes provide a more effective contraceptive with a decreased risk of escape ovulation compared to conventional dosing schemes. Most follicles ovulated in the immediate cycle following discontinuation of OC. We suggest that the delay to fertility following cessation of OC is not due to anovulation but other yet, unknown, biological factors. </p>

Antral ovarian folliculogenesis involves recruitment of a cohort of small follicles, physiological selection of a dominant follicle, and ovulation. The mechanism of selection has not been precisely determined. Identification of the timing of preovulatory selection is a key component in understanding natural and peri-menopausal ovarian function, ovarian suppression for contraception, and improvement of ovarian stimulation protocols. Morphologic characteristics obtained by ultrasonography cannot be precisely quantitated by the human eye. Computer-assisted image analysis overcomes subjective human evaluation of ultrasonographic images.<p> The objectives of this research were to assess ultrasound image attributes of human dominant (DF) and 1st subordinate (SF1) ovarian follicles during natural menstrual cycles and following discontinuation of conventional and continuous oral contraceptives (OC). We utilized sophisticated computer algorithms to elucidate an association between image attributes and physiologic status of follicles. Transvaginal ultrasonographic images obtained in 2 previous studies were used to quantify changes that occur in ovarian follicles.<p> We detected quantitative differences between the dominant and largest subordinate follicles of ovulatory and major anovulatory follicular waves, as well as during the first wave following OC discontinuation. Differences in ultrasonographic image attributes were associated with the physiological status of follicles. Evidence of follicular dominance in follicles which develop during major ovulatory waves or following OC discontinuation can be detected prior to the time of selection manifest by differences in dominant and subordinate follicle diameters. In addition, differences in quantitative image attributes were detected between ovulatory and anovulatory DF. Follicles that develop following conventional and continuous OC administration schemes exhibit the same image characteristics.<p> Further research is necessary to elucidate the exact correlation of follicle image attributes during all stages of development with histological characteristics, prediction of the timing of DF selection and the effects of different OC formulations on follicle development during and following OC cessation. Computer-assisted image analysis of ultrasound images has the potential to develop into a diagnostic, prognostic, and research tool for the in vivo evaluation of ovarian physiology and pathology and elucidate biologically important times such as physiologic selection, ovulation of DF and characterization of abnormal follicles (i.e., follicular cysts, luteinized unovulated follicles).

<p>The objective of this research was to assess ultrasound image attributes of human dominant ovarian follicles in the final stages of development during natural and oral contraceptive (OC) cycles, as well as characterize ovarian follicular and endometrial development during and after continuous versus conventional dosing schemes. We utilized sophisticated computer algorithms to elucidate an association between image attributes and physiologic status of follicles in their final stage of development. We used transvaginal ultrasonography to quantify changes in the numbers and diameters of ovarian follicles and changes in endometrial thickness and pattern during and following discontinuation of two different regimens of OC. Developmental changes in ovarian follicles and corpora lutea were correlated with serum estradiol-17â and progesterone, respectively to provide a comprehensive approach to examining ovarian and uterine function. </p><p>We reported for the first time that follicles which develop during natural and OC cycles have similar image attributes, which provides preliminary evidence that image attributes of human follicles are associated with physiologic status during the growth phase. Further research should be performed to elucidate the exact correlation between image attributes during all stages of follicular development throughout the menstrual cycle, prediction of dysfunctional follicular development (i.e., hemorrhagic anovulatory follicles) and the effects of different OC formulations on follicle development. Once the association between image attributes and various scenarios of follicular development are determined, a computer program could be developed to assess follicular health with a single ultrasound examination, obviating many ethical constraints that currently prevent large scale progress in ovarian follicular research. We further documented that continuous OC administration schemes provide greater follicular suppression than conventional dosing schemes. No dominant follicles developed during three consecutive 28 day cycles of continuous OC use, whereas eight dominant follicles developed during the same time period of conventional OC use. We interpreted these findings to mean that continuous OC dosing schemes provide a more effective contraceptive with a decreased risk of escape ovulation compared to conventional dosing schemes. Most follicles ovulated in the immediate cycle following discontinuation of OC. We suggest that the delay to fertility following cessation of OC is not due to anovulation but other yet, unknown, biological factors. </p>