https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:15653 Wed 11 Apr 2018 17:40:40 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:15122 Wed 11 Apr 2018 15:13:29 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18882 Wed 11 Apr 2018 15:08:03 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27762 in vitro fertilization (IVF) success. Furthermore, reduced expression of HSPA2 from the human sperm proteome leads to an impaired capacity for cumulus matrix dispersal, sperm-egg recognition and fertilization following both IVF and ICSI. In this review, we consider the evidence supporting the role of HSPA2 in sperm function and explore the potential mechanisms by which it is depleted in the spermatozoa of infertile patients. Such information offers novel insights into the molecular mechanisms governing sperm function.]]> Wed 11 Apr 2018 13:54:40 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30804 Wed 11 Apr 2018 12:10:05 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:33905 Tnfa, mitogen-activated protein kinase 8 (Mapk8/Jnk1), and growth differentiation factor 9 (Gdf9) (P < 0.05). Mass spectrometry and cell signaling pathway analysis indicated upregulation of cellular pathways associated with acute phase signaling, and cellular survival and assembly. Apoptosis assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling indicated significantly increased positive staining in the ovaries of LPS-treated neonates. These findings suggest that increased proinflammatory signaling within the neonatal ovary may be responsible for the LPS-induced depletion of the primordial follicle pool. These findings also have implications for female reproductive health, as the ovarian reserve is a major determinate of female reproductive longevity.]]> Wed 09 Feb 2022 15:58:52 AEDT ]]> 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:42488 Chlamydia infection, in both females and males, is increasing worldwide. Male infections have been associated clinically with urethritis, epididymitis, and orchitis, believed to be caused by ascending infection, although the impact of infection on male fertility remains controversial. Using a mouse model of male chlamydial infection, we show that all the major testicular cell populations, germ cells, Sertoli cells, Leydig cells, and testicular macrophages can be productively infected. Furthermore, sperm isolated from vas deferens of infected mice also had increased levels of DNA damage as early as 4 weeks post-infection. Bilateral vasectomy, prior to infection, did not affect the chlamydial load recovered from testes at 2, 4, and 8 weeks post-infection, and Chlamydia-infected macrophages were detectable in blood and the testes as soon as 3 days post-infection. Partial depletion of macrophages with clodronate liposomes significantly reduced the testicular chlamydial burden, consistent with a hematogenous route of infection, with Chlamydia transported to the testes in infected macrophages. These data suggest that macrophages serve as Trojan horses, transporting Chlamydia from the penile urethra to the testes within 3 days of infection, bypassing the entire male reproductive tract. In the testes, infected macrophages likely transfer infection to Leydig, Sertoli, and germ cells, causing sperm DNA damage and impaired spermatogenesis.]]> Tue 23 Aug 2022 15:34:32 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38608 Chlamydia is the most common sexually transmitted bacterial pathogen worldwide. Male and female infections occur at similar rates and both cause serious pathological sequelae. Despite this, the impact of chlamydial infection on male fertility has long been debated, and the effects of paternal chlamydial infection on offspring development are unknown. Using a male mouse chronic infection model, we show that chlamydial infection persists in the testes, adversely affecting the testicular environment. Infection increased leukocyte infiltration, disrupted the blood:testis barrier and reduced spermiogenic cell numbers and seminiferous tubule volume. Sperm from infected mice had decreased motility, increased abnormal morphology, decreased zona-binding capacity, and increased DNA damage. Serum anti-sperm antibodies were also increased. When both acutely and chronically infected male mice were bred with healthy female mice, 16.7% of pups displayed developmental abnormalities. Female offspring of chronically infected sires had smaller reproductive tracts than offspring of noninfected sires. The male pups of infected sires displayed delayed testicular development, with abnormalities in sperm vitality, motility, and sperm-oocyte binding evident at sexual maturity. These data suggest that chronic testicular Chlamydia infection can contribute to male infertility, which may have an intergenerational impact on sperm quality.]]> Thu 18 Nov 2021 11:59:22 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30490 Thu 03 Feb 2022 12:19:24 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17664 Sat 24 Mar 2018 07:57:48 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20323 Sat 24 Mar 2018 07:55:12 AEDT ]]> https://ogma.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://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30867 H)-one based Hedgehog signalling pathway (HSP) inhibitors we have developed two new classes of HSP inhibitors based on: L-tryptophan and benzo[1,3]dioxol-5-ylmethyl-[2-(1H-indol-3-yl)-ethyl]-amine. Synthesis of focused compound libraries identified six _L-tryptophan based inhibitors, and two stimulators, of Gli at 10 μM compound concentration. 2,4-Dichloro-13 and indole 16 suppressed mRNA expression of Ptch₁ in Shh LIGHT2 cells, with 13 suppressing and 16 stimulating Gli₂ mRNA expression. Focused library development of the benzo[1,3]dioxol-5-ylmethyl-[2-(1H-indol-3-yl)-ethyl]-amine scaffold afforded two sub-micro molar potent inhibitors of Gli expression with 5-methoxy-1H-indole-2-carboxylic acid benzo[1,3]dioxol-5-ylmethyl-[2-(1H-indol-3-yl)-ethyl]-amide 29 and 5-chloro-1H-indole-2-carboxylic acid benzo[1,3]dioxol-5-ylmethyl-[2-(1H-indol-3-yl)-ethyl]-amide 30 returning IC₅₀ values of 0.5 and 0.24 μM, respectively. Neither 29 nor 30 acted directly on Smo with our data supporting inhibition of the HSP downstream of Smo.]]> Sat 24 Mar 2018 07:26:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25153 Sat 24 Mar 2018 07:17:08 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36766 Fri 03 Jul 2020 14:13:41 AEST ]]>