Practical Considerations In Regenerative Medicine Research: Iacucs, Ethics, And The Use Of Animals In Stem Cell Studies, 2019 Colorado State University - Fort Collins
Practical Considerations In Regenerative Medicine Research: Iacucs, Ethics, And The Use Of Animals In Stem Cell Studies, Susan Vandewoude, Bernard E. Rollin
Bernard Rollin, PhD
The intent of US federal laws mandating IACUC review of animal-related activities was to satisfy contemporary socioethical concerns by introducing deliberations about ethics and animal welfare into the research process when animals are used. These laws and the system they chartered have worked well for the most part in providing opportunities for consideration of animal welfare as a vital part of animal research. As a result, investigators today are far less naïve about the ethical issues raised by research on animals and typically more sympathetic about the need for such consideration. As evidence of this growing awareness, the literature on ...
Beyond Pain—Controlling Suffering In Laboratory Animals, 2019 Colorado State University - Fort Collins
Beyond Pain—Controlling Suffering In Laboratory Animals, Bernard E. Rollin
Bernard Rollin, PhD
No abstract provided.
The Animal Research Controversy: Protest, Process & Public Policy, 2019 Tufts University
The Animal Research Controversy: Protest, Process & Public Policy, Andrew N. Rowan, Franklin M. Loew, Joan C. Weer
Andrew N. Rowan, DPhil
The controversy today regarding the use of animals in research appears on the surface to be a strongly polarized struggle between the scientific community and the animal protection movement. However, there is a wide range of opinions and philosophies on both sides. Mistrust between the factions has blossomed while communication has withered. Through the 1960s, 1970s and early 1980s, the animal movement grew in numbers and financial resources, and developed much greater public recognition and political clout. The research community paid relatively little attention to the animal movement for much of this period but, alarmed by several public relations coups ...
“Everyday” Knowledge And A New Paradigm Of Animal Research, 2019 University of British Columbia
“Everyday” Knowledge And A New Paradigm Of Animal Research, David Fraser, Jeffrey M. Spooner, Catherine A. Schuppli
David Fraser, PhD
Commentary on Marino and Allen (2017) The Psychology of Cows
Act On The Registration And Evaluation Of Chemicals (K-Reach) And Replacement, Reduction Or Refinement Best Practices, Soojin Ha, Troy Seidle, Kyung-Min Lim
Troy Seidle, PhD
Objectives - Korea’s Act on the Registration and Evaluation of Chemicals (K-REACH) was enacted for the protection of human health and the environment in 2015. Considering that about 2000 new substances are introduced annually across the globe, the extent of animal testing requirement could be overwhelming unless regulators and companies work proactively to institute and enforce global best practices to replace, reduce or refine animal use. In this review, the way to reduce the animal use for K-REACH is discussed. Methods - Background of the enforcement of the K-REACH and its details was reviewed along with the papers and regulatory documents ...
Mental Stress From Animal Experiments: A Survey With Korean Researchers, 2019 Ewha Womans University
Mental Stress From Animal Experiments: A Survey With Korean Researchers, Minji Kang, Ahram Han, Da-Eun Kim, Troy Seidle, Kyung-Min Lim, Seungjin Bae
Troy Seidle, PhD
Animal experiments have been widely conducted in the life sciences for more than a century, and have long been a subject of ethical and societal controversy due to the deliberate infliction of harm upon sentient animals. However, the harmful use of animals may also negatively impact the mental health of researchers themselves. We sought to evaluate the anxiety level of researchers engaged in animal use to analyse the mental stress from animal testing. The State Anxiety Scale of the State-Trait Anxiety Inventory (STAI) was used to evaluate how researchers feel when they conduct animal, as opposed to non-animal, based experiments ...
Non-Invasive Methods Of Identifying And Tracking Wild Squid, 2019 Medical University of Vienna
Non-Invasive Methods Of Identifying And Tracking Wild Squid, Ruth A. Byrne, James B. Wood, Roland C. Anderson, Ulrike Griebel, Jennifer A. Mather
Jennifer Mather, PhD
The ability to identify individual free-living animals in the field is an important method for studying their behavior. Apart from invasive external or internal tags, which may cause injury or abnormal behavior, most cephalopods cannot be tagged, as their skin is too soft and delicate for tag retention. Additionally, cephalopods remove many types of tags. However, body markings have been successfully used as a non invasive method to identify individuals of many different species of animals, including whale sharks, grey whales, seals, and zebras. We developed methods to sex and individually identify Caribbean reef squid, Sepiotheuthis sepioidea. Males showed distinct ...
Animal Organs In Humans: Uncalculated Risks And Unanswered Questions, 2019 British Union for the Abolition of Vivisection
Animal Organs In Humans: Uncalculated Risks And Unanswered Questions, Gillian R. Langley, Joyce D'Silva
Gill Langley, PhD
This report, produced jointly by the British Union for the Abolition of Vivisection and Compassion in World Farming, fills a number of significant gaps in the current debate about xenotransplantation.
In this report we also summarise the ethical and welfare issues concerning experiments on animals for xenotransplant research and their possible use as source animals for organs. Both these aspects are responsible for much pain and distress caused to many animals. We prefer the term “source animals” to “donor animals”, because animals do not choose to donate their organs for xenotransplantation.
The Impact Of Dietary Supplementation Of Arginine During Gestation In A Commercial Swine Herd: I. Gilt Reproductive Performance, Elizabeth A. Hines, Matthew R. Romoser, Zoë E. Kiefer, Aileen F. Keating, Lance H. Baumgard, Jarad Niemi, Nicholas K. Gabler, John F. Patience, Benjamin Haberl, Noel H. Williams, Brian J. Kerr, Kevin J. Touchette, Jason W. Ross
Supplemental Arg during gestation purportedly benefits fetal development. However, the benefits of a gestational Arg dietary strategy in commercial production are unclear. Therefore, objectives of this study examined Arg supplementation during different gestational stages and the effects on gilt reproductive performance. Pubertal gilts (n = 548) were allocated into four treatment groups: Control (n = 143; 0% supplemental Arg) or one of three supplemental Arg (1% as fed) treatments: from 15 to 45 d of gestation (n = 138; Early-Arg); from 15 d of gestation until farrowing (n = 139; Full-Arg); or from 85 d of gestation until farrowing (n = 128; Late-Arg). At farrowing ...
Ovarian Metabolism Of Xenobiotics, 2019 Iowa State University
Ovarian Metabolism Of Xenobiotics, Poulomi Bhattacharya, Aileen F. Keating
At birth, the mammalian ovary contains a finite number of primordial follicles, which once depleted, cannot be replaced. Xenobiotic exposures can destroy primordial follicles resulting in premature ovarian failure and, consequently, early entry into menopause. A number of chemical classes can induce premature ovarian failure, including environmental, chemotherapeutic and industrial exposures. While our knowledge on the mechanistic events that occur in the ovary with chemical exposures is increasing, our understanding of the ovary's capacity to metabolize such compounds is less established. This review will focus on three chemicals for which information on ovarian metabolism is known: trichloroethylene, 7,12-dimethylbenz ...
Distribution And Responsiveness Of Rat Anti-Müllerian Hormone During Ovarian Development And Vcd-Induced Ovotoxicity, Connie J. Mark-Kappeler, Nivedita Sen, Aileen F. Keating, I. Glenn Sipes, Patricia B. Hoyer
Anti-Müllerian hormone (AMH) is produced by granulosa cells in primary to small antral follicles of the adult ovary and helps maintain primordial follicles in a dormant state. The industrial chemical, 4-vinylcyclohexene diepoxide (VCD) causes specific ovotoxicity in primordial and small primary follicles of mice and rats. Previous studies suggest that this ovotoxicity involves acceleration of primordial to primary follicle recruitment via interactions with the Kit/Kit ligand signaling pathway. Because of its accepted role in inhibiting primordial follicle recruitment, the present study was designed to investigate a possible interaction between AMH and VCD-induced ovotoxicity. Protein distribution of AMH was compared ...
Dual Protective Role For Glutathione S-Transferase Class Pi Against Vcd-Induced Ovotoxicity In The Rat Ovary, 2019 Iowa State University
Dual Protective Role For Glutathione S-Transferase Class Pi Against Vcd-Induced Ovotoxicity In The Rat Ovary, Aileen F. Keating, Nivedita Sen, I. Glenn Sipes, Patricia B. Hoyer
The occupational chemical 4-vinylcyclohexene diepoxide (VCD) selectively destroys ovarian small pre-antral follicles in rats and mice via apoptosis. Detoxification of VCD can occur through glutathione conjugation, catalyzed by glutathione S-transferase (GST) enzymes. Further, GST class pi (GSTp) can negatively regulate JNK activity through protein:protein interactions in extraovarian tissues. Dissociation of this protein complex in the face of chemical exposure releases the inhibition of pro-apoptotic JNK. Increased JNK activity during VCD-induced ovotoxicity has been shown in isolated ovarian small pre-antral follicles following in vivo dosing of rats (80mg/ Kg/d; 15d, i.p). The present study investigated the pattern of ...
Inhibition Of Pik3 Signaling Pathway Members By The Ovotoxicant 4-Vinylcyclohexene Diepoxide In Rats, 2019 Iowa State University
Inhibition Of Pik3 Signaling Pathway Members By The Ovotoxicant 4-Vinylcyclohexene Diepoxide In Rats, Aileen F. Keating, Shannon M. Fernandez, Connie J. Mark-Kappeler, Nivedita Sen, I. Glenn Sipes, Patricia B. Hoyer
4-Vinylcyclohexene diepoxide (VCD), an occupational chemical that specifically destroys primordial and small primary follicles in the ovaries of rats and mice, is thought to target an oocyte-expressed tyrosine kinase receptor, Kit. This study compared the temporal effect of VCD on protein distribution of KIT and its downstream PIK3-activated proteins, AKT and FOXO3. Postnatal Day 4 Fischer 344 rat ovaries were cultured in control media ± VCD (30 μM) for 2–8 days (d2–d8). KIT, AKT, phosphorylated AKT, FOXO3, and pFOXO3 protein levels were assessed by Western blotting and/or immunofluorescence staining with confocal microscopy. Phosphorylated AKT was decreased (P < 0.05) in oocyte nuclei in primordial (39% decrease) and small primary (37% decrease) follicles within 2 days of VCD exposure. After d4, VCD reduced (P ...
Impact Of Obesity On 7,12-Dimethylbenz[A]Anthracene-Induced Altered Ovarian Connexin Gap Junction Proteins In Female Mice, Shanthi Ganesan, Jackson Nteeba, Aileen F. Keating
The ovarian gap junction proteins alpha 4 (GJA4 or connexin 37; CX37), alpha 1 (GJA1 or connexin 43; CX43) and gamma 1 (GJC1 or connexin 45; CX45) are involved in cell communication and folliculogenesis. 7,12-dimethylbenz[a]anthracene (DMBA) alters Cx37 and Cx43 expression in cultured neonatal rat ovaries. Additionally, obesity has an additive effect on DMBA-induced ovarian cell death and follicle depletion, thus, we investigated in vivo impacts of obesity and DMBA on CX protein levels. Ovaries were collected from lean and obese mice aged 6, 12, 18, or 24 wks. A subset of 18 wk old mice (lean ...
High Fat Diet Induced Obesity Alters Ovarian Phosphatidylinositol-3 Kinase Signaling Gene Expression, 2019 Iowa State University
High Fat Diet Induced Obesity Alters Ovarian Phosphatidylinositol-3 Kinase Signaling Gene Expression, J. Nteeba, J. W. Ross, J. W. Perfield Ii, A. F. Keating
Insulin regulates ovarian phosphatidylinositol-3-kinase (PI3K) signaling, important for primordial follicle viability and growth activation. This study investigated diet-induced obesity impacts on: 1) insulin receptor (Insr) and insulin receptor substrate 1 (Irs1); 2) PI3K components (Kit ligand (Kitlg), kit (c-Kit), protein kinase B alpha (Akt1) and forkhead transcription factor subfamily 3 (Foxo3a)); 3) xenobiotic biotransformation (microsomal epoxide hydrolase (Ephx1), Cytochrome P450 isoform 2E1 (Cyp2e1), Glutathione S-transferase (Gst) isoforms mu (Gstm) and pi (Gstp)) and 4) microRNA’s 184, 205, 103 and 21 gene expression. INSR, GSTM and GSTP protein levels were also measured. Obese mouse ovaries had decreased Irs1, Foxo3a, Cyp2e1 ...
Heat Stress Alters Ovarian Insulin-Mediated Phosphatidylinositol-3 Kinase And Steroidogenic Signaling In Gilt Ovaries, Jackson Nteeba, M. Victoria Sanz-Fernandez, Robert P. Rhoads, Lance H. Baumgard, Jason W. Ross, Aileen F. Keating
Heat Stress (HS) compromises a variety of reproductive functions in several mammalian species. Inexplicably, HS animals are frequently hyperinsulinemic despite marked hyperthermia-induced hypophagia. Our objectives were to determine the effects of HS on insulin signaling and components essential to steroid biosynthesis in the pig ovary. Female pigs (35±4 kg) were exposed to constant thermal neutral (TN; 20°C; 35-50% humidity; n = 6) or HS conditions (35°C; 20-35% humidity; n = 6) for either 7 (n = 10) or 35 d (n = 12). After 7d, HS increased (P < 0.05) ovarian mRNA abundance of the insulin receptor (INSR), insulin receptor substrate 1 (IRS1), protein kinase B subunit 1 (AKT1), low density lipoprotein receptor (LDLR), luteinizing hormone receptor (LHCGR), and aromatase (CYP19a). After 35d, HS increased INSR, IRS1, AKT1, LDLR, LHCGR, CYP19a, and steroidogenic acute regulatory protein (STAR) ovarian mRNA abundance. In addition, after 35d, HS increased ovarian phosphorylated IRS1 (pIRS1), phosphorylated AKT (pAKT), STAR and CYP19a protein abundance. Immunostaining analysis revealed similar localization of INSR and pAKT1 in the cytoplasmic membrane and oocyte cytoplasm, respectively, of all stage follicles, and in theca and granulosa cells. Collectively, these results demonstrate that HS alters ovarian insulin mediated-PI3K signaling pathway members which likely impacts follicle activation and viability. In summary, environmentally-induced HS is an endocrine disrupting exposure that modifies ovarian physiology and potentially compromises production of ovarian hormones essential for fertility and pregnancy maintenance.
A Comparison Of Inflammatory And Oxidative Stress Markers In Adipose Tissue From Weight-Matched Obese Male And Female Mice, Karen J. Nickelson, Kelly L. Stromsdorfer, R. Taylor Pickering, Tzu-Wen Liu, Laura C. Ortinau, Aileen F. Keating, James W. Perfield Ii
Expansion of intra-abdominal adipose tissue and the accompanying inflammatory response has been put forward as a unifying link between obesity and the development of chronic diseases. However, an apparent sexual dimorphism exists between obesity and chronic disease risk due to differences in the distribution and abundance of adipose tissue. A range of experimental protocols have been employed to demonstrate the role of estrogen in regulating health benefits; however, most studies are confounded by significant differences in body weight and adiposity. Therefore, the purpose of this study was to compare weight-matched obese male and female mice to determine if the sex-dependent ...
Impact Of Obesity On Ovotoxicity Induced By 7,12-Dimethylbenz[A]Anthracene In Mice, 2019 Iowa State University
Impact Of Obesity On Ovotoxicity Induced By 7,12-Dimethylbenz[A]Anthracene In Mice, Jackson Nteeba, Shanthi Ganesan, Aileen F. Keating
Insulin, elevated during obesity, regulates xenobiotic biotransformation enzymes, potentially through phosphatidylinositol 3-kinase (PI3K) signaling, in extraovarian tissues. PI3K regulates oocyte viability, follicular activation, and ovarian chemical biotransformation. 7,12-Dimethylbenz[a]anthracene (DMBA), a carcinogen and ovotoxicant, destroys all stages of follicles, leading to premature ovarian failure. Obesity has been reported to promote DMBA-induced tumors, but it remains unknown whether obesity affects ovarian xenobiotic metabolism. Therefore, we investigated ovarian expression of xenobiotic metabolism genes—microsomal epoxide hydrolase (Ephx1), glutathione S-transferase (GST) class Pi (Gstp1) and class mu 1 (Gstm1), and PI3K-signaling members (protein kinase B [AKT] alpha [Akt1], beta [Akt2], and ...
Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, 2019 University of Alberta
Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas
Pharmacy Faculty Articles and Research
Recent evidence supports involvement of amylin and the amylin receptor in the pathogenesis of Alzheimer’s disease (AD). We have previously shown that amylin receptor antagonist, AC253, improves spatial memory in AD mouse models. Herein, we generated and screened a peptide library and identified two short sequence amylin peptides (12–14 aa) that are proteolytically stable, brain penetrant when administered intraperitoneally, neuroprotective against Aβ toxicity and restore diminished levels of hippocampal long term potentiation in AD mice. Systemic administration of the peptides for five weeks in aged 5XFAD mice improved spatial memory, reduced amyloid plaque burden, and neuroinflammation. The common ...
Phosphoramide Mustard Exposure Induces Dna Adduct Formation And The Dna Damage Repair Response In Rat Ovarian Granulosa Cells, Shanthi Ganesan, Aileen F. Keating
Phosphoramide mustard (PM), the ovotoxic metabolite of the anti-cancer agent cyclophosphamide (CPA), destroys rapidly dividing cells by forming NOR-G-OH, NOR-G and G-NOR-G adducts with DNA, potentially leading to DNA damage. A previous study demonstrated that PM induces ovarian DNA damage in rat ovaries. To investigate whether PM induces DNA adduct formation, DNA damage and induction of the DNA repair response, rat spontaneously immortalized granulosa cells (SIGCs) were treated with vehicle control (1% DMSO) or PM (3 or 6 μM) for 24 or 48 h. Cell viability was reduced (P < 0.05) after 48 h of exposure to 3 or 6 μM PM. The NOR-G-OH DNA adduct was detected after 24 h of 6 μM PM exposure, while the more cytotoxic G-NOR-G DNA adduct was formed after 48 h by exposure to both PM concentrations. Phosphorylated H2AX (γH2AX), a marker of DNA double stranded break occurrence, was also increased by PM exposure, coincident with DNA adduct formation. Additionally, induction of genes (Atm, Parp1, Prkdc, Xrcc6, and Brca1) and proteins (ATM, γH2AX, PARP-1, PRKDC, XRCC6, and BRCA1) involved in DNA repair were observed in both a time- and dose-dependent manner. These data support that PM induces DNA adduct formation in ovarian granulosa cells, induces DNA damage and elicits the ovarian DNA repair response.