Effects of puberty and gonadotropins on the molecular events controlling meiotic resumption of mouse oocytes

Abstract

Although studies suggest that the low competence of oocytes from prepubertal animals is due to their insufficient cytoplasmic maturation and that FSH improves oocyte maturation possibly by retarding meiotic progression and allowing more time for cytoplasmic maturation, the mechanisms by which puberty and gonadotropins regulate meiotic progression require additional detailed studies. For the first time, we observed that while meiotic progression was significantly slower, the maturation-promoting factor (MPF) activity of oocytes was significantly higher in prepubertal than in adult mice. To resolve this contradiction, we specified the molecules regulating the MPF activity and their localization during oocyte maturation in prepubertal and adult mice primed with or without gonadotropins. Our tests using corresponding enzyme regulators suggested that while activities of protein kinase A were unaffected, the activity of adenylate cyclase (ADCY) and phosphodiesterase increased while cell division cycle 2 homolog A (CDC2A) decreased significantly after puberty. While most of the adult oocytes had CDC2A protein concentrated in the germinal vesicle (GV) region, the majority of prepubertal oocytes showed no nuclear concentration of CDC2A. Maximally priming mice with equine chorionic gonadotropin brought the above parameters of prepubertal oocytes close to those in adult oocytes. Together, the results suggest that puberty and gonadotropin control oocyte meiotic progression mainly by regulating the ADCY activity and the concentration of the activated MPF toward the GV region.

Cyclic AMP Affects Oocyte Maturation and Embryo Development in Prepubertal and Adult Cattle

“…The low cAMP levels prior to and after IVM in adult and prepubertal oocytes cultured without cAMP modulators, indicate that cAMP levels drop immediately after follicle aspiration and then remain at low levels through meiosis under in vitro conditions. Our results provide compelling evidence that prepubertal oocytes produce and/or receive cAMP from cumulus cells in response to cAMP modulators similar to adult oocytes, suggesting that this pathway is already functional in prepubertal bovine oocytes, which is in apparent contrast to previous reports in mice and pig prepubertal models [ 3 , 4 ].…”

“…Cyclic AMP controls meiotic progression in fetal ovaries, and is involved in the establishment of the primordial follicle pool [ 2 ]. However, the ability to accumulate cAMP is reduced in oocytes from prepubertal pigs [ 3 ] and mice [ 4 ]. Since the oocyte receives cAMP from the adjacent cumulus cells via gap junctions, the lower cAMP levels associated with lower developmental capacity in prepubertal oocytes have been linked either to decreased LH/FSH ovarian receptor expression [ 5 ], altered adenylate cyclase response [ 4 ], different phosphodiesterase (PDE) activities [ 4 ], and/or defective gap junction communication [ 6 ].…”

Regulation of Asymmetrical Cytokinesis by cAMP during Meiosis I in Mouse Oocytes

“…To rule out the possibility that these cytokinetic disorders were secondary to delayed GVBD, we performed a set of drug treatment experiments on post-GVBD oocytes. To further confirm that the abnormal cytokinetic results were directly caused by cAMP and its downstream factors, we treated post-GVBD oocytes with a adenylate cyclase activator, forskolin [43], [44], [45], and a PKA inhibitor, H-89 [46], [47], to determine their effects on cytokinesis. As shown in Figure 2, all three cAMP-elevating chemicals promoted both the “2-cell” and “1-cell” type division patterns.…”

Brilliant Cresyl Blue stain selects largest oocytes with highest mitochondrial activity, maturation-promoting factor activity and embryo developmental competence in prepubertal sheep

“…It has been shown that incompetent goat oocytes have a limited amount of cyclin B1 (Hue et al 1997) and p34 cdc2 . MPF activity in calf and lamb oocytes were significantly lower than in cow and ewe oocytes (Ledda et al 2001, Salamone et al 2001, whereas (Han et al 2010) showed in mice that the MPF activity of prepubertal oocytes was significantly higher than that of adult oocytes. In prepubertal goats, Anguita et al (2007) showed higher MPF activity and oocyte competence to develop up to the blastocyst stage in oocytes with a diameter larger than 135 mm.…”