Tressed mice as compared to stressed mice (P = 0.015). Compared to control mice, there was still a Microcystin-LR cost significant decrease in the retrieved oocytes number in the BDNF-treated stressed mice (P = 0.033). There are no significant differences in the oocyte maturation and early embryo cleavage between groups 1326631 (P.0.05 for all comparisons).DiscussionThe objective of this study was to evaluate the effects of chronic stress on ovarian BDNF expression and oocytes developmental potential. The major findings were that chronic unpredictable stress decreased the BDNF expression in antral follicles, but didn’t affect the BDNF expression in primary and secondary follicles. Chronic unpredictable stress also decreased the number of retrieved oocytes and subsequent oocytes developmental potential, which was rescued by exogenous BDNF treatment. In the present studies, we induced psychosocial stress in mice using chronic unpredictable mild stress [14]. The initial activity of an animal placed in a novel surrounding (ie open field activity) has long been taken as an indicator of its psychological and emotional state [17]. For example, spending longer time in peripheral squares of the open filed indicates an anxiety-like activity, and reduced locomotion and exploratory activity represent a loss of interest in new stimulating situations, implying a deficit in motivation [17,21]. The open field activity of the mice in our study implicated that the mice were in an anxious emotional and psychological state after chronic unpredictable stress. These data is consistent with our previous study [9,15]. Consistent with the previous report [14], the animal model in our study also showed signs of increased activity in the HPA axis, SPDP including increased CRH neurons in PVN of hypothalamus and corticosterone hypersecretion from adrenal. The behavioral performance in open-field and the HPA axis hyperactivity of the mice in our study implicated that the stress model was established successfully. BDNF, one of the neurotrophins, was originally described in the nervous system but has been shown to be expressed in a variety of nonneuronal tissues including endocrine tissues recently. The4. Chronic Unpredictable Stress Decreased the Oocytes Developmental Potential, while Treatment with BDNF Restored the Oocytes Developmental Potential in Stressed MiceBlastocyst formation rates are associated with oocytes developmental potential. Representative images of blastocyst formations inStress on Ovarian BDNF and Oocytes DevelopmentFigure 5. The effect of chronic stress and BDNF on the oocytes developmental potential. Figure 5 shows the representative oocytes formation in control (A), stressed (B), BDNF-treated (C) and BDNF-treated stressed (D) group. The presented data in figure 5E are average oocytes formation rate (mean 6 SEM) (n = 9). *** P,0.001 vs. control group. doi:10.1371/journal.pone.0052331.gpresence and secretion of BDNF from follicular cells in the human ovary were confirmed for the first time in 2002 [3]. Consistent with the previous report [6], our data showed a regional difference in the BDNF distribution in ovaries. The intensity of BDNF immunoreactivity in granulose cells was stronger in antral follicles 18325633 than that in early follicles. A large number of studies had suggested that BDNF in the nervous system is a stress-responsive intercellular messenger that may be an important component of the stress response [11,22,23]. Furthermore, our data revealed for the first time that BDNF.Tressed mice as compared to stressed mice (P = 0.015). Compared to control mice, there was still a significant decrease in the retrieved oocytes number in the BDNF-treated stressed mice (P = 0.033). There are no significant differences in the oocyte maturation and early embryo cleavage between groups 1326631 (P.0.05 for all comparisons).DiscussionThe objective of this study was to evaluate the effects of chronic stress on ovarian BDNF expression and oocytes developmental potential. The major findings were that chronic unpredictable stress decreased the BDNF expression in antral follicles, but didn’t affect the BDNF expression in primary and secondary follicles. Chronic unpredictable stress also decreased the number of retrieved oocytes and subsequent oocytes developmental potential, which was rescued by exogenous BDNF treatment. In the present studies, we induced psychosocial stress in mice using chronic unpredictable mild stress [14]. The initial activity of an animal placed in a novel surrounding (ie open field activity) has long been taken as an indicator of its psychological and emotional state [17]. For example, spending longer time in peripheral squares of the open filed indicates an anxiety-like activity, and reduced locomotion and exploratory activity represent a loss of interest in new stimulating situations, implying a deficit in motivation [17,21]. The open field activity of the mice in our study implicated that the mice were in an anxious emotional and psychological state after chronic unpredictable stress. These data is consistent with our previous study [9,15]. Consistent with the previous report [14], the animal model in our study also showed signs of increased activity in the HPA axis, including increased CRH neurons in PVN of hypothalamus and corticosterone hypersecretion from adrenal. The behavioral performance in open-field and the HPA axis hyperactivity of the mice in our study implicated that the stress model was established successfully. BDNF, one of the neurotrophins, was originally described in the nervous system but has been shown to be expressed in a variety of nonneuronal tissues including endocrine tissues recently. The4. Chronic Unpredictable Stress Decreased the Oocytes Developmental Potential, while Treatment with BDNF Restored the Oocytes Developmental Potential in Stressed MiceBlastocyst formation rates are associated with oocytes developmental potential. Representative images of blastocyst formations inStress on Ovarian BDNF and Oocytes DevelopmentFigure 5. The effect of chronic stress and BDNF on the oocytes developmental potential. Figure 5 shows the representative oocytes formation in control (A), stressed (B), BDNF-treated (C) and BDNF-treated stressed (D) group. The presented data in figure 5E are average oocytes formation rate (mean 6 SEM) (n = 9). *** P,0.001 vs. control group. doi:10.1371/journal.pone.0052331.gpresence and secretion of BDNF from follicular cells in the human ovary were confirmed for the first time in 2002 [3]. Consistent with the previous report [6], our data showed a regional difference in the BDNF distribution in ovaries. The intensity of BDNF immunoreactivity in granulose cells was stronger in antral follicles 18325633 than that in early follicles. A large number of studies had suggested that BDNF in the nervous system is a stress-responsive intercellular messenger that may be an important component of the stress response [11,22,23]. Furthermore, our data revealed for the first time that BDNF.
