Inhibition of follicular development induced by chronic unpredictable stress is associated with growth and differentiation factor 9 and gonadotropin in mice.
Chronic psychosocial stress negatively affects ovarian function. Ovarian follicular development is regulated by both pituitary-derived gonadotropins and intraovarian regulatory factors. To date, the suppressive effects of chronic stress on the ovary have been observed to be manifested mainly as an inhibition of gonadotropin release. It is not clear whether there are any other intraovarian regulatory mechanisms involved in this process. Growth and differentiation factor 9 (GDF9) is an important, oocyte-specific paracrine regulator required for follicular development. In this study, the chronic unpredictable mild stress model was used to produce psychosocial stress in mice. The number of different developmental stages of follicles was counted on ovarian sections stained with hematoxylin and eosin. Real-time PCR and Western blotting were used to detect the mRNA and protein levels, respectively, of GDF9. The results show that chronic unpredictable stress inhibits follicular development, increases follicular atresia, and suppresses GDF9 expression. Exogenous gonadotropin treatment partly restores the repressed antral follicular development, but has no effect on the repressed secondary follicular development associated with chronic stress. Treatment with recombinant GDF9 restores secondary follicular development. Cotreatments with GDF9 and gonadotropins restore both secondary and antral follicular development in stressed mice. These findings demonstrate that inhibition of follicular development induced by chronic unpredictable stress is associated with GDF9 and gonadotropin.
Center for Reproductive Medicine, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China. wlm@ustc.edu.cn
Li-Min
LM
Wu
Yu-Sheng
YS
Liu
Xian-Hong
XH
Tong
Ni
N
Shen
Ren-Tao
RT
Jin
Hui
H
Han
Mei-Hong
MH
Hu
Wei
W
Wang
Gui-Xiang
GX
Zhou
D000818:Animals; D005260:Female; D005496:Follicular Atresia / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D020869:Gene Expression Profiling; D006062:Gonadotropins / Q000502:physiology*; D055429:Growth Differentiation Factor 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism*
C525898:Gdf9 protein, mouse; D006062:Gonadotropins; D055429:Growth Differentiation Factor 9; D012333:RNA, Messenger