Developmental and Reproductive Toxicology

Parker, Robert M.; York, Raymond G.

doi:10.1002/9781118517000.ch15

Cited by 3 publications

(3 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…38 Dogs reach sexual maturity at a range of 8 to 12 months of age. [39][40][41] Under our current company practices, dogs for 1month GLP studies are started on study at 9 to 10 months of age and are at least 8 months of age for any toxicology study. Nonetheless, incomplete sexual maturation at microscopic examination of tissue remains an occasional finding that may impact the utility of miRNAs as biomarkers for toxicity.…”

Section: Discussionmentioning

confidence: 99%

Small RNA Sequencing to Discover Circulating MicroRNA Biomarkers of Testicular Toxicity in Dogs

et al. 2020

View full text Add to dashboard Cite

Predictive indicators of testicular toxicity could improve drug development by allowing early in-life screening for this adverse effect before it becomes severe. We hypothesized that circulating microRNAs (miRNAs) could serve as testicular toxicity biomarkers in dogs. Herein, we describe the results of an exploratory study conducted to discover biomarkers of drug-induced testicular injury. Following a dose-selection study using the testicular toxicant ethylene glycol monomethyl ether (EGME), we chose a dose of 50 mg/kg/d EGME to avoid systemic toxicity and treated 2 groups of dogs (castrated, non-castrated) for 14 to 28 days. Castrated animals were used as negative controls to identify biomarkers specific for testicular toxicity because EGME can cause toxicity to organ systems in addition to the testis. Blood was collected daily during the dosing period, followed by recovery for 29 to 43 days with less frequent sampling. Dosing was well tolerated, resulting in mild-to-moderate degeneration in testes and epididymides. Global profiling of serum miRNAs at selected dosing and recovery time points was completed by small RNA sequencing. Bioinformatics data analysis using linear modeling demonstrated several circulating miRNAs that were differentially abundant during the dosing period compared with baseline and/or castrated control samples. Confirmatory reverse transcription quantitative polymerase chain reaction data in these animals was unable to detect sustained alterations of miRNAs in serum, except for 1 potential candidate cfa-miR-146b. Taken together, we report the results of a comprehensive exploratory study and suggest future directions for follow-up research to address the challenge of developing diagnostic biomarkers of testicular toxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Small RNA Sequencing to Discover Circulating MicroRNA Biomarkers of Testicular Toxicity in Dogs

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Multiple references were provided for additional information on comparative organ system development (Beckman and Feuston 2003; Hew and Keller 2003; Holsapple, West, and Landreth 2003; Marty et al 2003; Walthall et al 2005; Watson et al 2006; Wood, Beyer, and Cappon 2003; Zoetis and Hurtt 2003a, 2003b; Zoetis et al 2003), developmental and reproductive toxicology (Bailey et al 2009; Greaves 2012; Haschek, Rousseaux, and Wallig 2013; Hoberman and Lewis 2012; Hood and Parker 2008; Lerman et al 2009; R. M. Parker 2014a, 2012; R. M. Parker and York 2013; Wise et al 2009; York et al 2014), and juvenile toxicology (Bailey and Mariën 2011; Cappon 2011; Cappon et al 2009; Carleer and Karres 2011; Hurtt 2011; Leconte et al 2011; R.…”

Section: Opening Remarks and Clinical Regulatory And Toxicology Permentioning

confidence: 99%

“…;Greaves 2012;Haschek, Rousseaux, and Wallig 2013;Hoberman and Lewis 2012;Hood and Parker 2008;Lerman et al 2009; R. M. Parker 2014a, 2012; R. M Parker and York 2013;Wise et al 2009;York et al 2014),. and juvenile toxicology(Bailey and Mariën 2011;Cappon 2011;Cappon et al 2009;Carleer and Karres 2011;Hurtt 2011;Leconte et al 2011;R.…”

mentioning

confidence: 99%

Juvenile Toxicology

Remick¹,

Catlin

Quist

et al. 2015

Toxicol Pathol

View full text Add to dashboard Cite

The Society of Toxicologic Pathology (STP) Education Committee and the STP Reproductive Special Interest Group held a North Carolina regional meeting entitled, “Juvenile Toxicology: Relevance and Challenges for Toxicologists and Pathologists” on March 13, 2015, at the National Institute of Environmental Health Sciences/National Toxicology Program in Research Triangle Park, North Carolina. The purpose of this regional meeting was to familiarize attendees with the topic of juvenile toxicity testing and discuss its relevance to clinical pediatric medicine, regulatory perspectives, challenges of appropriate study design confronted by toxicologists, and challenges of histopathologic examination and interpretation of juvenile tissues faced by pathologists. The 1-day meeting was a success with over 60 attendees representing industry, government, research organizations, and academia.

show abstract

Points to Consider in Designing and Conducting Juvenile Toxicology Studies

et al. 2017

Self Cite

View full text Add to dashboard Cite

In support of a clinical trial in the pediatric population, available nonclinical and clinical data provide input on the study design and safety monitoring considerations. When the existing data are lacking to support the safety of the planned pediatric clinical trial, a juvenile animal toxicity study is likely required. Usually a single relevant species, preferably a rodent, is chosen as the species of choice, while a nonrodent species can be appropriate when scientifically justified. Juvenile toxicology studies, in general, are complicated both conceptually and logistically. Development in young animals is a continuous process with different organs maturing at different rates and time. Structural and functional maturational differences have been shown to affect drug safety. Key points to consider in conducting a juvenile toxicology study include a comparative development of the organ systems, differences in the pharmacokinetics/absorption, distribution, metabolism, excretion (PK/ADME) profiles of the drug between young animal and child, and logistical requirement in the juvenile study design. The purpose of this publication is to note pertinent points to consider when designing and conducting juvenile toxicology studies and to aid in future modifications and enhancements of these studies to enable a superior predictability of safety of medicines in the pediatric population.

show abstract

Developmental and Reproductive Toxicology

Cited by 3 publications

References 27 publications

Small RNA Sequencing to Discover Circulating MicroRNA Biomarkers of Testicular Toxicity in Dogs

Small RNA Sequencing to Discover Circulating MicroRNA Biomarkers of Testicular Toxicity in Dogs

Juvenile Toxicology

Points to Consider in Designing and Conducting Juvenile Toxicology Studies

Contact Info

Product

Resources

About