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Zebrafish embryo assays are used by pharmaceutical and chemical companies as new approach methodologies (NAMs) in developmental toxicity screening. Despite an overall high concordance of zebrafish embryo assays with in vivo mammalian studies, false negative and false positive results have been reported. False negative results in risk assessment models are of particular concern for human safety, as developmental anomalies may be missed. Interestingly, for several chemicals and drugs that were reported to be false negative in zebrafish, skeletal findings were noted in the in vivo studies. As the number of skeletal endpoints assessed in zebrafish is very limited compared to the in vivo mammalian studies, the aim of this study was to investigate whether the sensitivity could be increased by including a skeletal staining method. Three staining methods were tested on zebrafish embryos that were exposed to four teratogens that caused skeletal anomalies in rats and/or rabbits and were false negative in zebrafish embryo assays. These methods included a fixed alizarin red-alcian blue staining, a calcein staining, and a live alizarin red staining. The results showed a high variability in staining intensity of larvae exposed to mammalian skeletal teratogens, as well as variability between control larvae originating from the same clutch of zebrafish. Hence, biological variability in (onset of) bone development in zebrafish hampers the detection of (subtle) treatment-related bone effects that are not picked-up by gross morphology. In conclusion, the used skeletal staining methods did not increase the sensitivity of zebrafish embryo developmental toxicity assays., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Steven Van Cruchten reports financial support was provided by University of Antwerp. Jonathan Ball reports financial support and equipment, drugs, or supplies were provided by University of Exeter. Steven Van Cruchten is Associate Editor for Reproductive Toxicology and Guest Editor for the Special Issue on NAMs for DART testing If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The human placenta is a critical life-support system that nourishes and protects a rapidly growing fetus; a unique organ, species specific in structure and function. We consider the pressing challenge of providing additional advice on the safety of prescription medicines and environmental exposures in pregnancy and how ex vivo and in vitro human placental models might be advanced to reproducible human placental test systems (HPTSs), refining a weight of evidence to the guidance given around compound risk assessment during pregnancy. The placental pharmacokinetics of xenobiotic transfer, dysregulated placental function in pregnancy-related pathologies and influx/efflux transporter polymorphisms are a few caveats that could be addressed by HPTSs, not the specific focus of current mammalian reproductive toxicology systems. An international consortium, "PlaNet", will bridge academia, industry and regulators to consider screen ability and standardisation issues surrounding these models, with proven reproducibility for introduction into industrial and clinical practice., (Copyright © 2016 Elsevier Inc. All rights reserved.)

There is increasing evidence to indicate that a substantial number of both man-made and naturally occurring chemicals are disruptive to human and wildlife reproductive health. Currently, reproductive toxicology testing is primarily carried out in vivo, however, in the past 50 years, various culture methods have been developed with the aim of growing ovarian follicles in vitro. These culture systems have become a widely used tool in reproductive biology and toxicology. In this review we describe how reproductive toxicology of the ovary is greatly enhanced by in vitro studies. Experiments using in vitro ovarian cultures to understand or detect damage to the ovary itself and to its specialised structures of the follicles and oocytes, allows for faster screening of potential developmental and/or reproductive toxicants., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Currently, in pre and postnatal development studies or in juvenile rat studies, bone growth is assessed "for cause" by simple measurements of long bone length in vivo and at termination. This manuscript compares two radiographic methods for in vivo assessment of long bones in suckling rats; 2D imaging using a Faxitron™ and 3D imaging using μCT. This paper illustrates that it is possible to image the unanaesthetised postnatal day 1 rat by Faxitron™ using a simple Micropore™ tape restraint method. With isoflurane anaesthesia, it was possible to obtain high quality μCT images of pups from day of birth. No pups were rejected by their mothers following either technique. The Faxitron™ was straightforward and fast, however the μCT 3D images were of greater overall utility. Either method could be used for longitudinal investigation of long bone observations made previously in embryofetal development studies, or for other mechanistic work., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The importance of the role of cilia in pre and post natal development has been appreciated since the previous century. However, a better understanding of the physiological and, conversely, dysfunctional role that cilia have in developmental disease is still emerging. Dysfunctioning cilia can lead to diseases with a remarkable spectrum of phenotypes ranging from embryofetal lethality, through "classic" organ malformation to severe loss of function that leads to diseases during infancy or more subtle loss of function that may not become apparent until adulthood. Collectively, these diseased are termed ciliopathies. A shift in the focus of research by using tools and models that highlight the similarity between the genetics of mice, zebrafish and human cells, is starting to form an interesting mechanistic picture of how cilia have a role in the developmental pathologies and human diseases. Some of the underlying cellular principles, implicated genes and, where possible, mechanisms will be briefly described in this manuscript and there are several more detailed reviews available [Quinlan et al, 2008; Veland et al, 2009 and Norris and Grimes, 2013]., (Copyright © 2014. Published by Elsevier Inc.)