Abstract
General senescence of the adult organism is closely connected with reproductive one. Meanwhile, the age-related reduction in the female fertility is primarily associated with a decline in the gamete quality. Molecular and cellular changes in oocytes of old mammalian females are very similar to those occurring during aging of matured ova of their young counterparts, suggesting similarities in underlying mechanisms. The aim of the present work was to study actions of two related pituitary hormones, prolactin (PRL) and growth hormone (GH), on age-associated modifications of metaphase-II (M-II) chromosomes in bovine oocytes using a model of the prolonged culture. We analyzed: (1) effects of PRL and GH on abnormal changes in the chromosome morphology in aging matured oocytes and the role of cumulus cells in these effects and (2) signaling pathways involved in the hormone actions. During the prolonged culture of oocytes, a gradual rise in the frequency of destructive modifications of M-II chromosomes was revealed. In the case of cumulus-enclosed oocytes (CEOs), PRL and GH exerted dose-dependent biphasic effects on the frequency of these modifications. Both PRL (50 ng/ml) and GH (10 ng/ml) decelerated the abnormal chromosome changes in CEOs, but did not affect the chromosome configuration in denuded oocytes. Concurrently, the presence of PRL and GH receptors in cumulus cells surrounding matured oocytes was demonstrated. Attenuating effects of both hormones on the chromosome modifications in aging CEOs were abolished by PP2 (an inhibitor of Src-family tyrosine kinases), triciribine (an inhibitor of Akt kinase), and calphostin C (a protein kinase C inhibitor). Our findings indicate that PRL and GH can exert the similar decelerating action on age-associated alterations in the M-II chromosome morphology in bovine ova, which is mediated by cumulus cells and may be related to activation of Src-family tyrosine kinases as well as Akt- and protein kinase C-dependent signal pathways.
Highlights
General senescence of the adult organism is closely connected with reproductive one
The application of PRL at concentrations of 20−50 ng/mL caused a decline in the frequency of M-II chromosome modifications, with the maximum reducing effect being observed at a concentration of 50 ng/mL (Figure 2A)
The present research has been directed toward elucidating the pattern and mechanisms of action of two closely-related pituitary hormones, PRL and growth hormone (GH), on abnormal modifications of M-II chromosomes in matured bovine oocytes aging in vitro
Summary
General senescence of the adult organism is closely connected with reproductive one. It is well established that the female reproductive performance, primarily the ovarian function, deteriorates with age in many vertebrates including humans, with underlying fundamental mechanisms being conserved among species (Finch and Holmes, 2010; Ottinger, 2010). Postovulatory aging of mature mammalian oocytes is another biological phenomenon leading to an age-related decline in the quality of female gametes This type of senescence occurs quickly (within 1–2 days) in ova arrested at the metaphase-II (M-II) stage in the absence of activation stimuli (Miao et al, 2009). According to the current state of knowledge, molecular transformations occurring in the oocyte cytoplasm underlie the above listed negative functional changes These transformations are primarily related to alterations in the pattern of synthesis and post-translational modifications of effector proteins and to disturbances of the mitochondrial function and calcium homeostasis (EichenlaubRitter et al, 2004; Tatone et al, 2006, 2008; Miao et al, 2009; McReynolds et al, 2012). The prolonged culture of mature mammalian oocytes is a convenient model for the comprehensive study of physiological factors and signal systems involved in regulation of the oocyte senescence
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