Browsing by Subject "Germ Cells"

Now showing 1 - 5 of 5
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    Association between donor gamete use and supernumerary embryo disposition decisions.
    (Journal of assisted reproduction and genetics, 2023-02) Tsai, Shelun; Hynes, Jenna S; Zanolli, Nicole; Raburn, Douglas; Steiner, Anne Z

    Purpose

    The aim of this study is to determine if donor gamete use is associated with patients' decisions regarding disposition of supernumerary embryos.

    Methods

    Patients who intended to undergo an IVF cycle at a single academic center signed an embryo disposition consent form to indicate their disposition preferences for any supernumerary embryos. A retrospective chart review was performed to obtain the embryo disposition declarations and demographic information. The primary outcome was the distribution of embryo disposition choices between patients who used donor gametes compared to patients who did not use donor gametes. Fisher's exact test was used to compare groups. Logistic regression models were created to determine the association between donor gamete use and disposition decision after adjusting for patient age, body mass index, and nulliparity.

    Results

    Five hundred six patients were included. Ninety-one (18.0%) patients used donor gametes [46 (9.0%) donor oocytes, 52 (10.3%) donor sperm]. Patients using donor gametes differed from those not using donor gametes when making decisions concerning death of the patient (P < 0.01), simultaneous death (P = 0.04), separation (P < 0.01), discontinuation of ART (P = 0.01), and time-limited storage (P < 0.01). Most patients, regardless of donor or autologous gamete use, awarded embryos to themselves or their partner if given the option. For patients who did not choose this option, excess embryos were generally awarded to research or discarded rather than donating to another couple. Patients using donor gametes were more likely to award embryos to research over discarding.

    Conclusion

    Patients using donor gametes made different choices regarding supernumerary embryo disposition compared to patients not using donor gametes.
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    Loss of LDAH associated with prostate cancer and hearing loss.
    (Human molecular genetics, 2018-12) Currall, Benjamin B; Chen, Ming; Sallari, Richard C; Cotter, Maura; Wong, Kristen E; Robertson, Nahid G; Penney, Kathryn L; Lunardi, Andrea; Reschke, Markus; Hickox, Ann E; Yin, Yanbo; Wong, Garrett T; Fung, Jacqueline; Brown, Kerry K; Williamson, Robin E; Sinnott-Armstrong, Nicholas A; Kammin, Tammy; Ivanov, Andrew; Zepeda-Mendoza, Cinthya J; Shen, Jun; Quade, Bradley J; Signoretti, Sabina; Arnos, Kathleen S; Banks, Alexander S; Patsopoulos, Nikolaos; Liberman, M Charles; Kellis, Manolis; Pandolfi, Pier Paolo; Morton, Cynthia C
    Great strides in gene discovery have been made using a multitude of methods to associate phenotypes with genetic variants, but there still remains a substantial gap between observed symptoms and identified genetic defects. Herein, we use the convergence of various genetic and genomic techniques to investigate the underpinnings of a constellation of phenotypes that include prostate cancer (PCa) and sensorineural hearing loss (SNHL) in a human subject. Through interrogation of the subject's de novo, germline, balanced chromosomal translocation, we first identify a correlation between his disorders and a poorly annotated gene known as lipid droplet associated hydrolase (LDAH). Using data repositories of both germline and somatic variants, we identify convergent genomic evidence that substantiates a correlation between loss of LDAH and PCa. This correlation is validated through both in vitro and in vivo models that show loss of LDAH results in increased risk of PCa and, to a lesser extent, SNHL. By leveraging convergent evidence in emerging genomic data, we hypothesize that loss of LDAH is involved in PCa and other phenotypes observed in support of a genotype-phenotype association in an n-of-one human subject.
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    The RNA-binding protein DND1 acts Sequentially as a negative regulator of pluripotency and a positive regulator of epigenetic modifiers required for germ cell reprogramming.
    (Development (Cambridge, England), 2019-06-28) Ruthig, Victor A; Friedersdorf, Matthew B; Garness, Jason A; Munger, Steve C; Bunce, Corey; Keene, Jack D; Capel, Blanche
    The adult spermatogonial stem cell population arises from pluripotent primordial germ cells (PGCs) that enter the fetal testis around embryonic day (E)10.5. PGCs undergo rapid mitotic proliferation, then enter prolonged cell cycle arrest (G1/G0) during which they transition to pro-spermatogonia. In mice homozygous for the Ter mutation in the RNA-binding protein Dnd1 (Dnd1 Ter/Ter ), many male germ cells (MGCs) fail to enter G1/G0, and form teratomas, tumors containing many embryonic cell types. To investigate the origin of these tumors, we sequenced the MGC transcriptome in Dnd1 Ter/Ter mutants at E12.5, E13.5, and E14.5, just prior to teratoma formation, and correlated this information with DO-RIP-Seq identified DND1 direct targets. Consistent with previous results, we found DND1 controls down-regulation of many genes associated with pluripotency and active cell cycle, including mTor, Hippo and Bmp/Nodal signaling pathway elements. However, DND1 targets also include genes associated with male differentiation including a large group of chromatin regulators activated in wild type but not mutant MGCs during the E13.5 and E14.5 transition. Results suggest multiple DND1 functions, and link DND1 to initiation of epigenetic modifications in MGCs.
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    To grow or not to grow: nutritional control of development during Caenorhabditis elegans L1 arrest.
    (Genetics, 2013-07) Baugh, L Ryan
    It is widely appreciated that larvae of the nematode Caenorhabditis elegans arrest development by forming dauer larvae in response to multiple unfavorable environmental conditions. C. elegans larvae can also reversibly arrest development earlier, during the first larval stage (L1), in response to starvation. "L1 arrest" (also known as "L1 diapause") occurs without morphological modification but is accompanied by increased stress resistance. Caloric restriction and periodic fasting can extend adult lifespan, and developmental models are critical to understanding how the animal is buffered from fluctuations in nutrient availability, impacting lifespan. L1 arrest provides an opportunity to study nutritional control of development. Given its relevance to aging, diabetes, obesity and cancer, interest in L1 arrest is increasing, and signaling pathways and gene regulatory mechanisms controlling arrest and recovery have been characterized. Insulin-like signaling is a critical regulator, and it is modified by and acts through microRNAs. DAF-18/PTEN, AMP-activated kinase and fatty acid biosynthesis are also involved. The nervous system, epidermis, and intestine contribute systemically to regulation of arrest, but cell-autonomous signaling likely contributes to regulation in the germline. A relatively small number of genes affecting starvation survival during L1 arrest are known, and many of them also affect adult lifespan, reflecting a common genetic basis ripe for exploration. mRNA expression is well characterized during arrest, recovery, and normal L1 development, providing a metazoan model for nutritional control of gene expression. In particular, post-recruitment regulation of RNA polymerase II is under nutritional control, potentially contributing to a rapid and coordinated response to feeding. The phenomenology of L1 arrest will be reviewed, as well as regulation of developmental arrest and starvation survival by various signaling pathways and gene regulatory mechanisms.
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    Unfolded protein response genes regulated by CED-1 are required for Caenorhabditis elegans innate immunity.
    (2008) Haskins, Kylie Anne
    The first line of defense against pathogens is the phylogenetically ancient innate immune system. This system consists of physical barriers and conserved signaling pathways are activated upon infection to produce effector molecules that mount a microbicidal response. Recently, C. elegans has been established as a model organism for the study of innate immunity due to C. elegans genetic tractability and origins predating the evolution of adaptive immunity. Conserved defense pathways essential for mammalian innate immunity have been identified in C. elegans. However, most receptors critical for the activation of the defense signaling pathways in C. elegans remain unknown. The goal of this work was to study CED-1 and its potential role as a cell-surface signaling receptor essential for C. elegans immune response. In this study, we performed a full-genome microarray analysis and discovered that CED-1 functions to activate the expression of pqn/abu unfolded protein response (UPR) genes. The unfolded protein response has been implicated in the normal physiology of immune defense and in several disorders including diabetes, cancer, and neurodegenerative disease. Here we show that ced-1 and pqn/abu genes are required for the survival of C. elegans exposed to live S. enterica. We also show that the overexpression of pqn/abu genes confers protection to pathogen-mediated killing. Taken together, these results indicate that the apoptotic receptor CED-1 and a network of PQN/ABU proteins involved in a non-canonical UPR response are required for proper defense to pathogen infection in Caenorhabditis elegans.