https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47000 Wed 26 Jul 2023 09:22:27 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13348 Wed 11 Apr 2018 15:32:48 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26157 Wed 11 Apr 2018 13:31:01 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26928 Wed 11 Apr 2018 12:37:10 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27739 Wed 11 Apr 2018 11:56:44 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17518 Wed 11 Apr 2018 11:03:28 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14465 Wed 11 Apr 2018 10:57:57 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30799 Wed 11 Apr 2018 10:41:45 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35087 G) derived from the father introduce a premature STOP codon leading to a truncated protein. FANCM exhibits enhanced testicular expression. In control subjects, immunohistochemical staining localized FANCM to the Sertoli and spermatogenic cells of seminiferous tubules with increasing intensity through germ cell development. This is consistent with its role in maintaining genomic stability in meiosis and mitosis. In the individual with SCOS carrying bi-allelic FANCM LoF variants, none or only faint expression was detected in the Sertoli cells. As further evidence, we detected two additional NOA-affected case subjects with independent FANCM homozygous nonsense variants, one from Estonia (p.Gln1701*; rs147021911) and another from Portugal (p.Arg1931*; rs144567652). The study convincingly demonstrates that bi-allelic recessive LoF variants in FANCM cause azoospermia. FANCM pathogenic variants have also been linked with doubled risk of familial breast and ovarian cancer, providing an example mechanism for the association between infertility and cancer risk, supported by published data on Fancm mutant mouse models.]]> Wed 10 Nov 2021 15:05:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35422 Tue 30 Jul 2019 09:58:39 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27738 Tue 26 Feb 2019 13:24:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32666 capacitation in order to attain the competence to recognize the egg and then engage in a complex cascade of cell–cell interactions in order to achieve union of the gametes at fertilization. This process involves extensive remodelling of the sperm plasma membrane as well as the induction of hyperactivated motility and, as such, is a highly energy-dependent process. The process of spermatogenesis requires extensive remodelling of a conventional spherical cell to become one of the most highly specialized and morphologically differentiated cells in the body. During this transformation, the DNA in the sperm nucleus reaches the physical limits of compaction to achieve a quasicrystalline state. This extreme compaction requires the removal or resorption of most of the cytoplasm, at the same time removing the majority of the organelles (such as the endoplasmic reticulum, ribosomes and Golgi apparatus) that are intimately involved in the regulation of metabolism in somatic cells. The result of this extensive remodelling is that spermatozoa are left translationally and transcriptionally silent, as well as relatively depleted of intracellular enzymes and energy reserves such as fat droplets, yolk granules and glycogen. For this reason, spermatozoa are heavily dependent on their immediate extracellular environment for the energy substrates that drive metabolism, as well as a variety of specialized enzymatic activities that would normally be conducted intracellularly. For example, in somatic cells, the array of enzymes and low-molecular-mass scavengers involved in mediating protection against oxidative stress is housed intracellularly, largely within the cytoplasmic space. Spermatozoa, on the other hand, largely depend upon the epididymal and seminal plasmas to provide the richest and most diverse combination of antioxidants in the body, including several that are unique to the male reproductive tract. In much the same way that economies trade using a currency rather than a barter system, biological systems have all evolved their own unique ‘currencies’ for the exchange of energy.The most important of these currencies is adenosine 5’-triphosphate (ATP), which provides the metabolic energy to drive activities in all living cells.]]> Tue 10 Jul 2018 11:47:12 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33498 Tue 06 Nov 2018 11:19:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44824 Thu 27 Oct 2022 12:44:28 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34486 Thu 27 Jan 2022 15:56:27 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7319 Sat 24 Mar 2018 08:38:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1016 Sat 24 Mar 2018 08:29:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1172 Sat 24 Mar 2018 08:28:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:2500 Sat 24 Mar 2018 08:27:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19083 Sat 24 Mar 2018 08:05:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20774 6 by cNLS Mapper), while 8 nuclear proteins lacked any cNLS. In addition, we developed a new strategy to predict which cargoes bind to importin a through the conserved C-terminal acidic domain (ARM repeats 9-10), and provided functional validation of a predicted importin α C-terminal binding segment in Senataxin and Smarca4. Evaluation of this set of candidate binding partners from spermatogenic cells using several bioinformatics approaches provides new evidence that individual importin αs may serve unique and nonredundant roles in mediating cellular differentiation.]]> Sat 24 Mar 2018 08:00:22 AEDT ]]> https://nova.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://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20270 Sat 24 Mar 2018 07:59:54 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21602 cko) in somatic testicular cells to define the molecular mechanisms involved in the development of the testicular phenotype observed in PJS patients. Focal vacuolization in some of the seminiferous tubules was observed in 4-week-old mutant testes but germ cell development appeared to be normal. However, similar to PJS patients, we observed progressive germ cell loss and Sertoli cell only tubules in Lkb1^cko testes from mice older than 10 weeks, accompanied by defects in Sertoli cell polarity and testicular junctional complexes and decreased activation of the MAP/microtubule affinity regulating and focal adhesion kinases. Suppression of AMP kinase and activation of mammalian target of rapamycin (mTOR) signaling were also observed in Lkb1^cko testes. Loss of Tsc1 or Tsc2 copies the progressive Lkb1^cko phenotype, suggesting that dysregulated activation of mTOR contributes to the pathogenesis of the Lkb1^cko testicular phenotype. Pten^cko mice had a normal testicular phenotype, which could be explained by the comparative lack of mTOR activation detected. These studies describe the importance of LKB1 signaling in testicular biology and the possible molecular mechanisms driving the pathogenesis of the testicular defects observed in PJS patients.]]> Sat 24 Mar 2018 07:59:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19563 Sat 24 Mar 2018 07:58:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20640 Sat 24 Mar 2018 07:55:44 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20019 Sat 24 Mar 2018 07:50:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5181 Sat 24 Mar 2018 07:47:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5289 Sat 24 Mar 2018 07:46:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27749 Drosophila and also shown to be vital to sperm development and reproductive potential in the mouse. We focus in depth on the role and function of the vertebrate Musashi ortholog Musashi-1 (MSI1). Through detailed expression studies and utilizing our novel transgenic Msi1 testis-specific overexpression model, we have identified 2 unique RNA-binding targets of MSI1 in spermatogonia, Msi2 and Erh, and have demonstrated a role for MSI1 in translational regulation. We have also provided evidence to suggest that nuclear import protein, IPO5, facilitates the nuclear translocation of MSI1 to the transcriptionally silenced XY chromatin domain in meiotic pachytene spermatocytes, resulting in the release of MSI1 RNA-binding targets. This firmly establishes MSI1 as a master regulator of posttranscriptional control during early spermatogenesis and highlights the significance of the subcellular localization of RNA binding proteins in relation to their function.]]> Sat 24 Mar 2018 07:27:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:3443 Sat 24 Mar 2018 07:20:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22263 in vitro induction of acrosomal exocytosis by progesterone, but not by the calcium ionophore A23187, and elicited a concomitant reduction of in vitro fertilization. In vivo treatment with these inhibitors also resulted in spermatozoa displaying reduced acrosome reaction potential. Dynamin 1 and 2 phosphorylation increased on progesterone treatment, and this was also selectively blocked by dynasore. On the basis of our collective data, we propose that dynamin could regulate specific membrane fusion events necessary for acrosomal exocytosis in mouse spermatozoa.]]> Sat 24 Mar 2018 07:17:38 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25108 Sat 24 Mar 2018 07:17:15 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25153 Sat 24 Mar 2018 07:17:08 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24273 Sat 24 Mar 2018 07:14:56 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44770 Mon 24 Oct 2022 09:03:28 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47477 0.05). Collectively, our acute heat stress model supports the existence of heat susceptible stages of germ cell development, with the round spermatids being most perturbed and spermatogonial stem cells exhibiting resistance to this insult. Such findings were complemented by our chronic heat stress model, which further supported the vulnerability of the round spermatid population.]]> Mon 23 Jan 2023 11:33:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40758 Mon 18 Jul 2022 13:54:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37687 90% purity. Properties of these cultured adult Sertoli cells were then compared with those of cultured Sertoli cells derived from 20-day-old mice (also > 90% purity). By cell counting, bromo-2-deoxyuridine incorporation, and metaphase plate detection, we demonstrated that only adult Sertoli cells did not proliferate throughout 12 culture days. In contrast, Sertoli cells derived from 20-day-old mice still proliferated until Day 10 in culture. The morphology and profiles of intracellular lipidomics and spent medium proteomics of the 2 cultures were also different. Cultured adult Sertoli cells were larger in size and contained higher levels of triacylglycerols, cholesteryl esters, and seminolipid, and the proteins in their spent medium were mainly engaged in cellular metabolism. In contrast, proteins involved in cell division, including anti-Mullerian hormone, cell division cycle protein 42 (CDC42), and collagen isoforms, were at higher levels in Sertoli cell cultures derived from 20-day-old mice. Therefore, cultured Sertoli cells derived from 10-week-old mice, rather than those from 20-day-old animals, should be used for studies on properties of adult Sertoli cells.]]> Mon 15 Mar 2021 15:08:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46955 Mon 12 Dec 2022 09:05:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22598 Mon 10 Sep 2018 14:10:34 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42608 Snai2‐deficient mice provided evidence of deficient spermatogenesis. To address the hypothesis that Snail proteins are important for male fertility, this study provides the first comprehensive cellular expression profiles of all three mammalian Snail genes in the post‐natal mouse testis. To evaluate Snail transcript expression profiles, droplet digital (dd) PCR and in situ hybridization were employed. Snai1, 2 and 3 transcripts are readily detected at 7, 14, 28 days post‐partum (dpp) and 7 weeks (adult). Unique cellular expression was demonstrated for each by in situ hybridization and immunohistochemistry using Western blot‐validated antibodies. SNAI1 and SNAI2 are in the nucleus of the most mature germ cell types at post‐natal ages 10, 15 and 26. SNAI3 is only detected from 15 dpp onwards and is localized in the Sertoli cell cytoplasm. In the adult testis, Snai1 and Snai2 transcripts are detected in spermatogonia and spermatocytes, while Snai3 is in both germ and Sertoli cells. SNAI1 protein is evident in nuclei of spermatogonia, spermatocytes, round spermatids and elongated spermatids (Stages IX–XII). SNAI2 is present in the nuclei of spermatogonia and spermatocytes, with a faint signal detected in round spermatids. SNAI3 was detected only in Sertoli cell cytoplasm, as in juvenile testes. Additionally, colocalization of SNAI1 and SNAI2 with previously identified key binding partners, LSD1 and PRC2 complex components, provides strong evidence that these important functional interactions are conserved during spermatogenesis to control gene activity. These distinct expression profiles suggest that each Snail family member has unique functions during spermatogenesis.]]> Fri 26 Aug 2022 14:44:17 AEST ]]>