Meiotic Cell Cycle Progression in Mouse Oocytes: Role of Cyclins.

All eukaryotic cells, including oocytes, utilize an engine called cyclin-dependent kinase (Cdk) to drive the cell cycle. Cdks are activated by a co-factor called cyclin, which regulates their activity. The key Cdk-cyclin complex that regulates the oocyte cell cycle is known as Cdk1-cyclin B1. Recent studies have elucidated the roles of other cyclins, such as B2, B3, A2, and O, in oocyte cell cycle regulation. This review aims to discuss the recently discovered roles of various cyclins in mouse oocyte cell cycle regulation in accordance with the sequential progression of the cell cycle. In addition, this review addresses the translation and degradation of cyclins to modulate the activity of Cdks. Overall, the literature indicates that each cyclin performs unique and redundant functions at various stages of the cell cycle, while their expression and degradation are tightly regulated. Taken together, this review provides new insights into the regulatory role and function of cyclins in oocyte cell cycle progression.

NCKX3 was compensated by calcium transporting genes and bone resorption in a NCKX3 KO mouse model.

Gene knockout is the most powerful tool for determination of gene function or permanent modification of the phenotypic characteristics of an animal. Existing methods for gene disruption are limited by their efficiency, time required for completion and potential for confounding off-target effects. In this study, a rapid single-step approach to knockout of a targeted gene in mice using zinc-finger nucleases (ZFNs) was demonstrated for generation of mutant (knockout; KO) alleles. Specifically, ZFNs to target the sodium/calcium/potassium exchanger3 (NCKX3) gene in C57bl/6j were designed using the concept of this approach. NCKX3 KO mice were generated and the phenotypic characterization and molecular regulation of active calcium transporting genes was assessed when mice were fed different calcium diets during growth. General phenotypes such as body weight and plasma ion level showed no distinct abnormalities. Thus, the potassium/sodium/calcium exchanger of NCKX3 KO mice proceeded normally in this study. As a result, the compensatory molecular regulation of this mechanism was elucidated. Renal TRPV5 mRNA of NCKX3 KO mice increased in both male and female mice. Expression of TRPV6 mRNA was only down-regulated in the duodenum of male KO mice. Renal- and duodenal expression of PTHR and VDR were not changed; however, GR mRNA expression was increased in the kidney of NCKX3 KO mice. Depletion of the NCKX3 gene in a KO mouse model showed loss of bone mineral contents and increased plasma parathyroid hormone, suggesting that NCKX3 may play a role in regulating calcium homeostasis.

The Regulation of Fatty Acid Oxidation in Human Preeclampsia.

Preeclampsia (PE) is a pregnancy disorder characterized by high blood pressure, placental oxidative stress, and proteinuria. In a GeneFishing experiment using human preeclamptic placenta, expression of acyl-coenzyme A dehydrogenase very long chain (ACADVL), which is involved in fatty acid ß-oxidation (FAO), was detected. To investigate the correlation between PE and FAO, this study subjected in vitro BeWo cells and in vivo pregnant mice to oxidative stress induced by hypoxia. Hypoxic condition, which oxygen supply is insufficient in cells and placenta, created a similar state to placental oxidative stress in PE, as evidenced by increased hypoxic (oxoguanine DNA glycosylase 1, hypoxia inducible factor 1 alpha subunit) and preeclamptic markers (soluble fms-like tyrosine kinase 1) both in vitro and in vivo. Increased expression of FAO-related genes (ACADVL, enoyl-coenzyme A hydratase/3-hydroxyacyl coenzyme A dehydrogenase) was observed in these models as well as in cases of preeclamptic preterm labor. In the in vivo liver model, messenger RNA expression of gluconeogenesis-related genes increased. Consequently, these results suggest that expression of FAO-related genes is regulated by hypoxic conditions and onset time of PE and affects maternal gluconeogenesis during pregnancy in patients with PE.