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Biology subjects

Liew, S.

Publications and source records attributed to Liew, S..

2 recordsLinked to original sources

Moderate episodic prenatal alcohol does not impact female offspring fertility in rats

Prenatal alcohol exposure (PAE) has been associated with reproductive dysfunction in offspring. However, studies in females, particularly examining long-term infertility or impacts on ovarian reserve, are lacking. The current study utilised a moderate, episodic exposure model in rats to mimic special occasion drinking, which is reported to be common during pregnancy. Our objective was to examine the consequences of this prenatal alcohol exposure on reproductive parameters in female offspring. Pregnant Sprague Dawley rats were treated with either an ethanol gavage (1g EtOH/kg body weight), or an equivalent volume of saline, on embryonic days 13.5 and 14.5 of pregnancy, resulting in a peak blood alcohol concentration of [~]0.04%. Neonatal female offspring were examined for molecular markers regulating early follicle numbers in the ovary and unbiased stereology used to quantify primordial and early growing follicle numbers. Puberty onset (age at vaginal opening and first estrous) was measured post-weaning and estrous cycles, reproductive hormones (progesterone and estradiol) and pregnancy success measured in adults (5-6 months of age). We found no evidence that any of these reproductive parameters were significantly altered by PAE in this model. This animal study provides some reassurance for women who may have consumed a small amount of alcohol during their pregnancy. However, previously published effects on offspring metabolism using this model reinforce avoidance of alcohol during pregnancy.

developmental biology↗

Identification and Characterization of the First Fragment Hits for SETDB1 Tudor Domain

SET domain bifurcated protein 1 (SETDB1) is a human histone-lysine methyltransferase, which is amplified in human cancers and was shown to be crucial in the growth of non-small and small cell lung carcinoma. In addition to its catalytic domain, SETDB1 harbors a unique tandem tudor domain which recognizes histone sequences containing both methylated and acetylated lysines, and likely contributes to its localization on chromatin. Using X-ray crystallography and NMR spectroscopy fragment screening approaches, we have identified the first small molecule fragment hits that bind to histone peptide binding groove of the TTD of SETDB1. Herein, we describe the binding modes of these fragments and analogues and the biophysical characterization of key compounds. These confirmed small molecule fragments will inform the development of potent antagonists of SETDB1 interaction with histones.

pharmacology and toxicology↗