The possible FAT1‐mediated apoptotic pathways in porcine cumulus cells

Abstract

Porcine cumulus cells are localized around oocytes and act as a specific type of granulosa that plays essential roles in the development and maturation of oocytes, the development and atresia of follicles, and the development of embryos. Studies of FAT1 have demonstrated its functions in cell-cell contact, actin dynamics, and cell growth suppression. To understand whether the FAT1 gene affects the apoptosis of porcine cumulus cells and to elucidate the mechanism of this potential action, FAT1 was knocked down using RNA interference. The lack of FAT1 resulted in stable expression of CTNNB, enhanced expression of cleaved CASP3, but decreased the BCL2/BAX ratios at both the mRNA and protein levels. These results indicated that FAT1 inhibited porcine cumulus cell apoptosis via different pathways. Taken together, these data provide new insights into the mechanisms of the association between FAT1 and porcine cumulus cell apoptosis.

Screening and identification of critical transcription factors involved in the protection of cardiomyocytes against hydrogen peroxide-induced damage by Yixin-shu

“…To further reveal the role of Pbx3, its downstream genes were extensively analysed. The pro-survival genes Bcl9 40 , Fat1 41 and Arhgef12 42 were all significantly decreased, indicating that serious damage was caused by H 2 O 2 . Importantly, an increase in anti-apoptotic genes such as Arhgef12 42 , and Cenpf 43 and a decrease in pro-apoptotic genes such as Pbx1 52 was observed after YXS treatment, suggesting a potential protective role of Pbx3 in H 2 O 2 -induced injury.…”

“…For example, homeobox protein SIX1 (Six1) can inhibit apoptosis by decreasing caspase-3 expression 6 , and Forkhead box protein C1 (Foxc1) enhances apoptosis resistance during oxidative stress by targeting FOXO1 34 . Among identified seven TFs, anti-apoptotic TFs such as Apex1 28 , 35 , Pbx3 36 , 37 , Tfcp2 38 , and Arnt 33 were obviously repressed, and their target anti-apoptotic genes such as Asxl1 39 , Bcl9 40 , Fat1 41 and Arhgef12 42 were also down-regulated, indicating that cell apoptosis occurred at the molecular level after H 2 O 2 treatment. By contrast, YXS activated anti-apoptotic TFs such as Apex1, Pbx3, Tfcp2, and Arnt, and increased anti-apoptosis genes such as Asxl1, Arhgef12 42 and Cenpf 43 , demonstrating a vital protective role in H 2 O 2 -induced injury.…”

Molecular mechanisms of oogenesis

“…Некоторые исследователи отметили увеличение частоты аномального синапсиса у генетически аномальных плодов, как и ожидалось, а также ассоциировали некоторые хромосомные аномалии с увеличением апоптоза. Однако при исследовании отдельных ооцитов мыши в профазе первого деления мейоза обнаружили только незначительную связь между апоптозными молекулярными маркерами и нормальным или аномальным появлением SCF у мышей [7,18,19]. В отличие от относительного отсутствия ассоциации между апоптозными маркерами и мейотическими аномалиями в отдельных ооцитах, отмечали значительные различия в поведении образцов тканей яичников in vitro в соответствии с гестационным возрастом [20].…”

“…(2017) использовали методы культивирования органов, применяемые для взрослых тканей. Они наблюдали выживание и рост фолликулов in vitro из ткани 16-22-й и 22-23-й нед гестации соответственно и подтвердили мейотическую инициацию и прогрессию [19]. Оптимизация культуральных методов для плодных яичников станет ценным инструментом для изучения гормонального и паракринного влияний на ключевые аспекты развития яичников человека.…”

Glucose metabolism during in vitro maturation of mouse oocytes: An study using RNA interference

“…In the In this study, genes of G6PD and GAPDH in cumulus cells and genes of MPC1 and NDUFV1 in oocytes were silenced by RNAi to observe the roles of PPP and glycolysis in cumulus cells, and mitochondrial pyruvate transport and electron transport in oocytes, on in vitro maturation of mouse DOs. Although RNAi has been used to knock down genes in cumulus cells (Wu et al, 2017;Zhai et al, 2013), there is no report on its application to silence genes involved in glucose metabolism in these cells or in oocytes themselves. However, RNAi has been used to knock down glucose metabolism-related genes in other somatic cells.…”