FOXO3a is involved in the apoptosis of naked oocytes and oocytes of primordial follicles from neonatal rat ovaries.
ABSTRACT Inhibition of the forkhead transcription factor, FOXO3a, can promote the transition from primordial to primary follicle and subsequent follicle development in mammalian ovaries. Stem cell factor (SCF) initiates anti-apoptotic signaling from its membrane receptor, c-kit, to Bcl-2 family members through PI3K/AKT in oocytes of primordial follicles. However, whether FOXO3a mediates the apoptosis of naked oocytes and oocytes of primordial follicles remains unknown. In the present study, oocytes from nests and primordial follicles from neonatal rat ovaries were cultured, and oocyte apoptosis was examined using the TUNEL technique. The pro-apoptotic action of FOXO3a and the potential signal transduction pathways were investigated using RT-PCR, Western blot, and immunocytochemistry. Culturing oocytes in the presence of SCF did not affect the level of total FOXO3a protein, but rapidly elevated the level of phosphorylated FOXO3a (indicating functional suppression). As phosphorylated FOXO3a increased, oocyte apoptosis was inhibited. The specific PI3K/Akt inhibitor, LY 294002, abolished the phosphorylation of FOXO3a and the anti-apoptotic action of SCF. SCF down-regulated the expression of p27KIP1 and pro-apoptotic factors such as Bim, Bad, and Bax, and this activity was reversed by LY 294002. SCF up-regulated the expression of MnSOD, which was also inhibited by LY 294002. However, SCF had no effect on Bcl-2 protein. These results suggest that FOXO3a is involved in oocyte apoptosis in the neonatal rat ovary, and the SCF-PI3K/Akt-FOXO3a signaling pathway mediates oocyte apoptosis and primordial follicle formation.
- [Show abstract] [Hide abstract]
ABSTRACT: Objective To examine the effects of high-fat (HF) diet–induced maternal obesity on follicular population and gene expression in adult offspring ovaries. Design Experimental mouse study. Setting Laboratory. Animal(s) Mice on HF diet. Intervention(s) Female C57BL/6J mice were fed an HF or standard chow (C) diet 6 weeks before conception, through pregnancy and lactation. Offspring were fed the C or HF diet from weaning, creating the HF/HF, HF/C, C/HF, C/C offspring groups. Main Outcome Measure(s) Follicular counts and gene expression in adult offspring ovaries. Result(s) Prenatal exposure to maternal HF nutrition resulted in the reduction of primordial, antral, and Graafian follicle numbers in offspring ovaries (both HF/C and HF/HF). Expression levels of genes involved in apoptosis (FoXO3a), follicular growth and development (Gdf9), and circadian rhythms generation (Clock and Bmal1) were elevated in the ovaries of HF/C and HF/HF offspring, while expression of the circadian clock genes Cry1 and Per1 were lower in HF/HF ovaries. Conclusion(s) Maternal obesity during pregnancy has long-term deleterious consequences on follicular growth and development in the adult offspring ovaries, which may impact their reproductive potential.Fertility and Sterility 09/2014; DOI:10.1016/j.fertnstert.2014.06.015 · 4.30 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The complex [bis(8-quinolyloxyethyl)ether-H3+O]3[La(NO3)6] has been prepared and its structure has been determined by single-crystal X-ray diffraction. This compound represents an example of a hydronium ion complex with an acyclic bis(quinolyl)-terminated oligoether, which forms a counter ion for the complex anion [La(NO3)6]3-. The cations are stabilized by three hydrogen bonds. Copyright © 1996 Elsevier Science LtdPolyhedron 01/1996; 15(19):3219-3223. DOI:10.1016/0277-5387(96)00036-8 · 2.05 Impact Factor