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Biology subjects

Badey, N.

Publications and source records attributed to Badey, N..

2 recordsLinked to original sources

Human fallopian tube-on-a-chip for preclinical testing of non-hormonal contraceptives with living human sperm

The fallopian tube serves as a sperm reservoir, and it is the site where the oocytes become fertilized. Here, we describe development of an organ-on-a-chip microfluidic model of the fallopian tube (FT Chip) lined by primary human epithelial cells and stromal fibroblasts derived from the FT ampulla. Abundant tissue folds lined by hormone-responsive, epithelial cells resembling those seen in vivo formed on-chip, but not in epithelial organoids cultured in gel cultures. Comparative time-resolved analysis of human sperm versus oocyte-sized microparticles introduced into the epithelial channel in the presence of estradiol revealed that sperm movement was significantly reduced, while the oocyte-sized particles increased, relative to movements in acellular chips. When the non-hormonal contraceptive TDI-11861 was administered to the chip, dose-dependent inhibition of human sperm motility was detected. Thus, this FT Chip may offer a human preclinical tool to study FT physiology and assess the efficacy and mechanism of action of contraceptives.

cell biology↗

Engineering Asian elephant TP53: TP53 retrogene knockouts activate common and unique cancer-relevant pathways

Proboscideans have developed a suite of genetic changes including those responsible for tumor suppression and environmental adaptation. Here we examine a handful of woolly mammoth-specific deletions, and their potential contributions to arctic adaptation, as well as the expanded TP53 genetic repertoire in elephants. We use CRISPR-Cas9 to introduce mammoth-specific noncoding deletions as well as knockouts of TP53, all 29 TP53 retrogenes, or both in combination in Asian elephant cell lines, and examine the transcriptomic response. We find that many of the mammoth-specific deletions likely contribute to various arctic phenotypes including vascular development, metabolism and thermogenesis, and hair and skin adaptations. We also find that while there is considerable overlap in DNA damage responses of the TP53 and retrogene knockouts, retrogenes knockouts also exhibit strong enrichment of many extracellular pathways suggesting they may play a role in the tumor microenvironment and mitigating metastatic growth.

genetics↗