Retinoid signaling in skeletal development: Scoping the system for predictive toxicology

Knudsen, Thomas B.; Pierro, Jocylin D.; Baker, Nancy C.

doi:10.1016/j.reprotox.2020.10.014

Cited by 15 publications

(19 citation statements)

References 247 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The discovery of these proteins was due to their ability to induce bone and cartilage formation. BMPs are now thought of as a group of axial morphogenic messengers that harmonize tissue architecture throughout the body (47)(48)(49)(50).…”

Section: Discussionmentioning

confidence: 99%

The effect of cellular and physiological indicators on gender determination

Haje

2021

Cell Mol Biol (Noisy-le-grand)

View full text Add to dashboard Cite

Gender determination, in addition to having special value to parents, has particular importance in sex-linked diseases. This study aimed to investigate the cellular indicators (i.e. BMP-6 protein and PPAR? protein expression levels in granulosa cells) and the physiological indicators on gender determination. For this purpose, on 68 infertile patients referred to the clinic, ovarian stimulation was performed by different protocols and then ruptured by different HCG. Follow-up of patients was performed after they became pregnant after five months. U/S was done for knowing the gender of the baby then after labor rechecked another time. Also, granulosa-luteal cells (GLCs) were isolated from the follicular fluid of 68 women participating in the study. BMP-6 protein and PPAR? protein were measured using Western blotting. Results showed that the total number of delivered babies was 68, 41 males (60.3%) and 27 females (39.7%). About physiological indicators results, there was no significant association between the age of the mother and sex of the baby (P=0.934). No significant association was detected between the month during which the conception occurred and the sex of the baby (P=0.734). The same result was obtained for the follicle side (P=0.236), and follicle size (P=0.659), there was no significant association between the sex of the baby with the following factors: protocol of treatment (P=0.417), IVF after HCG (P=0.237), HCG type (P=0.572), parity (P=0.282), and type of infertility (P=0.376). The cellular indicators results showed that the BMP-6 protein level in granulosa cells of mothers with daughters was almost twice as high as mothers with sons (P=0.043). But there was no significant difference between mothers with daughters and mothers with sons in PPAR? protein level (P=0.12). It can be concluded that except for BMP-6 protein level, none of the cellular and physiological indicators affects gender determination. Therefore, this cell indicator can probably be evaluated as an effective indicator in determining gender.

show abstract

Section: Discussionmentioning

confidence: 99%

The effect of cellular and physiological indicators on gender determination

Haje

2021

Cell Mol Biol (Noisy-le-grand)

View full text Add to dashboard Cite

show abstract

“…A previous study compiled potential AOPs that cause skeletal defects from retinoid pathway disruption during embryonic development (Knudsen et al 2021). We took each of these AOP key events and built PubMed queries designed to retrieve the citations describing that key event's biological activity.…”

Section: Connecting the Chemicals To The Biological Literaturementioning

confidence: 99%

Identifying candidate reference chemicals for in vitro testing of the retinoid pathway for predictive developmental toxicity

Baker

Pierro

Taylor

et al. 2022

ALTEX

View full text Add to dashboard Cite

Evaluating chemicals for potential in vivo toxicity based on their in vitro bioactivity profile is an important step toward animal-free testing. A compendium of reference chemicals and data describing their bioactivity on specific molecular targets, cellular pathways, and biological processes is needed to bolster confidence in the predictive value of in vitro hazard detection. Endogenous signaling by all-trans retinoic acid (ATRA) is an important pathway in developmental processes and toxicities. Employing data extraction methods and advanced literature extraction tools, we assembled a set of candidate reference chemicals with demonstrated activity on ten protein family targets in the retinoid system. The compendium was culled from Protein Data Bank, ChEMBL, ToxCast/Tox21, and the biomedical literature in PubMed. Finally, we performed a case study on one chemical in our collection, citral, an inhibitor of endogenous ATRA production, to determine whether the literature would support an adverse outcome pathway explaining the compound's developmental toxicity initiated by disruption of the retinoid pathway. We also deliver an updated Abstract Sifter tool populated with these reference compounds and complex search terms designed to query the literature for the downstream consequences to support concordance with targeted retinoid pathway disruption.

show abstract

“…A recently published ‘Detailed Review Paper on the Retinoid Signaling Pathway’ (supported by the European Commission and OECD) included an annex focusing on both male and female reproduction ( OECD, 2021 ). But despite these efforts there are still no AOPs for disrupted RA signaling in the AOP-Knowledge Base (AOP-KB) even though several putative AOPs involving retinoid disruption have been suggested ( Draskau et al, 2020 , Johansson et al, 2020 , Knudsen et al, 2021 , Tonk et al, 2015 ). We currently have under development AOP 398 ‘Inhibition of ALDH1A (RALDH) causing reduced all-trans retinoic acid levels leading to impaired fertility’ and here describe a relevant KER that links reduced atRA levels with disrupted meiosis in fetal oocytes.…”

Section: Introductionmentioning

confidence: 99%