https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27033 Xenopus and is expressed during ovarian development in Drosophila. In mammals Musashi is important for spermatogenesis and male fertility, but its role in the ovary has yet to be characterized. In this study we determined the expression of mammalian Musashi proteins MSI1 and MSI2 during mouse folliculogenesis, and through the use of a MSI2-specific knockout mouse model we identified that MSI2 is essential for normal follicle development. Time-course characterization of MSI1 and MSI2 revealed distinct differences in steady-state mRNA levels and protein expression/localization at important developmental time-points during folliculogenesis. Using a gene-trap mouse model that inactivates Msi2, we observed a significant decrease in ovarian mass, and change in follicle-stage composition due to developmental blocking of antral stage follicles and pre-antral follicle loss through atresia. We also confirmed that hormonally stimulated Msi2-deficient mice produce significantly fewer MII oocytes (60.9% less than controls, p < 0.05). Furthermore, the majority of these oocytes are of poor viability (62.2% non-viable/apoptotic, p < 0.05), which causes a reduction in female fertility evidenced by decreased litter size in Msi2-deficient animals (33.1% reduction to controls, p < 0.05). Our findings indicate that MSI1 and MSI2 display distinct expression profiles during mammalian folliculogenesis and that MSI2 is required for pre-antral follicle development.]]> Wed 11 Apr 2018 16:39:10 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30985 Wed 11 Apr 2018 14:34:15 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26301 Wed 11 Apr 2018 14:11:17 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26480 Wed 11 Apr 2018 13:21:00 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29296 DEAD (Asp-Glu-Ala-Asp) box protein 4 (Ddx4) gene promoter. Histopathological and functional analysis of ovaries from these mutant mice (Ctnnb1^ex3cko) showed no defects in ovarian functions, oocytes, ovulation and early embryonic development. However, breeding of the Ctnnb1^ex3cko female mice with males of known fertility never resulted in birth of mutant pups. Examination of uteri from time pregnant mutant females revealed defects in ectoderm differentiation leading to abnormal foetal development and premature death. Collectively, our work has established the role of active WNT/βcatenin signalling in oocyte biology and foetal development, and provides novel insights into the possible mechanisms of complications in human pregnancy such as repeated spontaneous abortion, sudden intrauterine unexpected foetal death syndrome and stillbirth.]]> Wed 11 Apr 2018 13:03:48 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27739 Wed 11 Apr 2018 11:56:44 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21729 Fzr1 knockout mouse embryos show normal preimplantation development but die due to a lack of endoreduplication needed for placentation. However, interpretation of the role of FZR1 during this period is hindered by the presence of maternal stores. In this study, therefore, we used an oocyte-specific knockout to examine FZR1 function in early mouse embryo development. Maternal FZR1 was not crucial for completion of meiosis, and furthermore viable pups were born to Fzr1 knockout females mated with normal males. However, in early embryos the absence of both maternal and paternal FZR1 led to a dramatic loss in genome integrity, such that the majority of embryos arrested having undergone only a single mitotic division and contained many γ-H2AX foci, consistent with fragmented DNA. A prominent feature of such embryos was the establishment of two independent spindles following pronuclear fusion and thus a failure of the chromosomes to mix (syngamy). These generated binucleate 2-cell embryos. In the 10% of embryos that progressed to the 4-cell stage, division was so slow that compaction occurred prematurely. No embryo development to the blastocyst stage was ever observed. We conclude that Fzr1 is a surprisingly essential gene involved in the establishment of a single spindle from the two pronuclei in 1-cell embryos as well as being involved in the maintenance of genomic integrity during the mitotic divisions of early mammalian embryos.]]> Wed 11 Apr 2018 11:35:19 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30207 350 microRNAs (miRNAs), a developmentally important sRNA class, the majority (~60%) of which are also represented by the miRNA signature of spermatozoa. This includes >50 miRNAs that were found exclusively in epididymal sperm and epididymosomes, but not in the surrounding soma. We also documented substantial changes in the epididymosome miRNA cargo, including significant fold changes in almost half of the miRNAs along the length of the epididymis. Finally, we provide the first direct evidence for the transfer of several prominent miRNA species between mouse epididymosomes and spermatozoa to afford novel insight into a mechanism of intercellular communication by which the sRNA payload of sperm can be selectively modified during their post-testicular maturation.]]> Wed 11 Apr 2018 11:13:04 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45607 Wed 02 Nov 2022 14:14:14 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18182 Tue 23 Jun 2015 18:36:00 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35834 Kifc1 and Kifc5b, in aged oocytes; family members selectively targeted for expression regulation by endo-siRNAs of elevated abundance. The implications of reduced Kifc1 and Kifc5b expression were explored using complementary siRNA-mediated knockdown and pharmacological inhibition strategies, both of which led to increased rates of aneuploidy in otherwise healthy young oocytes. Collectively, our data raise the prospect that altered sRNA abundance, specifically endo-siRNA abundance, could influence the quality of the aged oocyte.]]> Tue 10 Dec 2019 16:34:23 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24275 Thu 17 Nov 2016 17:26:48 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30367 Thu 03 Feb 2022 12:18:59 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29938 Thu 03 Feb 2022 12:18:20 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:1294 Sat 24 Mar 2018 08:32:44 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:987 Sat 24 Mar 2018 08:29:49 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:11246 Cdh1) activity, which ubiquitylates and so targets cyclin B1 for degradation. Thus, APC^Cdh1 activity prevents precocious meiotic entry by promoting cyclin B1 degradation. However, it remains unresolved how cyclin B1 levels are suppressed sufficiently to maintain arrest but not so low that they make oocytes hormonally insensitive. Here, we examined spatial control of this process by determining the intracellular location of the proteins involved and using nuclear-targeted cyclin B1. We found that raising nuclear cyclin B1 concentrations, an event normally observed in the minutes before nuclear envelope breakdown, was a very effective method of inducing the G2/M transition. Oocytes expressed only the α-isoform of Cdh1, which was predominantly nuclear, as were Cdc27 and Psmd11, core components of the APC and the 26S proteasome, respectively. Furthermore, APC^Cdh1 activity appeared higher in the nucleus, as nuclear-targeted cyclin B1 was degraded at twice the rate of wild-type cyclin B1. We propose a simple spatial model of G2 arrest in which nuclear APC^Cdh1-proteasomal activity guards against any cyclin B1 accumulation mediated by nuclear import.]]> Sat 24 Mar 2018 08:10:55 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20838 Sat 24 Mar 2018 08:05:56 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21158 FZR1 activity in the male germline led to both a mitotic and a meiotic testicular defect resulting in infertility due to the absence of mature spermatozoa. Spermatogonia in the prepubertal testes of such mice had abnormal proliferation and delayed entry into meiosis. Although early recombination events were initiated, male germ cells failed to progress beyond zygotene and underwent apoptosis. Loss of APC/C^FZR1 activity was associated with raised cyclin B1 levels, suggesting that CDK1 may trigger apoptosis. By contrast, female FZR1Δ mice were subfertile, with premature onset of ovarian failure by 5 months of age. Germ cell loss occurred embryonically in the ovary, around the time of the zygotene-pachytene transition, similar to that observed in males. In addition, the transition of primordial follicles into the growing follicle pool in the neonatal ovary was abnormal, such that the primordial follicles were prematurely depleted. We conclude that APC/C^FZR1 is an essential regulator of spermatogonial proliferation and early meiotic prophase I in both male and female germ cells and is therefore important in establishing the reproductive health of adult male and female mammals.]]> Sat 24 Mar 2018 08:00:18 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20695 Sat 24 Mar 2018 07:55:41 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20166 Sat 24 Mar 2018 07:51:44 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18819 Sat 24 Mar 2018 07:51:08 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:6539 Sat 24 Mar 2018 07:48:19 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26158 Sat 24 Mar 2018 07:35:27 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21996 Sat 24 Mar 2018 07:14:33 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22692 Kpna1, Kpna2, Kpna3, Kpna4, Kpna6, Kpna7, Kpnb1, Ipo5 and Xpo1), all were expressed in the embryonic ovary with up-regulation of protein levels concomitant with meiotic entry for KPNA2, accompanied by the redistribution of the cellular localisation of KPNA2 and XPO1. In contrast, postnatal folliculogenesis revealed significant up-regulation of Kpna1, Kpna2, Kpna4, Kpna6 and Ipo5 and down-regulation of Kpnb1, Kpna7 and Xpo1 at the primordial to primary follicle transition. KPNAs exhibited different localisation patterns in both oocytes and granulosa cells during folliculogenesis, with three KPNAs – KPNA1, KPNA2 and IPO5 – displaying marked enrichment in the nucleus by antral follicle stage. Remarkably, varied subcellular expression profiles were also identified in isolated pre-ovulatory oocytes with KPNAs KPNA2, KPNB1 and IPO5 detected in the cytoplasm and at the nuclear rim and XPO1 in cytoplasmic aggregates. Intriguingly, meiotic spindle staining was also observed for KPNB1 and XPO1 in meiosis II eggs, implying roles for KPNAs outside of nucleo-cytoplasmic transport. Thus, we propose that KPNAs, by targeting specific cargoes, are likely to be key regulators of oocyte development.]]> Sat 24 Mar 2018 07:11:11 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20165 Mon 24 Aug 2015 15:22:23 AEST ]]>