TY - JOUR
T1 - Disruption of Tsc2 in oocytes leads to overactivation of the entire pool of primordial follicles
AU - Adhikari, Deepak
AU - Flohr, Gilian
AU - Gorre, Nagaraju
AU - Shen, Yan
AU - Yang, Hairu
AU - Lundin, Eva
AU - Lan, Zijian
AU - Gambello, Michael J.
AU - Liu, Kui
PY - 2009/10/20
Y1 - 2009/10/20
N2 - To maintain the length of reproductive life in a woman, it is essential that most of her ovarian primordial follicles are maintained in a quiescent state to provide a continuous supply of oocytes. However, our understanding of the molecular mechanisms that control the quiescence and activation of primordial follicles is still in its infancy. In this study, we provide some genetic evidence to show that the tumor suppressor tuberous sclerosis complex 2 (Tsc2), which negatively regulates mammalian target of rapamycin complex 1 (mTORC1), functions in oocytes to maintain the dormancy of primordial follicles. In mutant mice lacking the Tsc2 gene in oocytes, the pool of primordial follicles is activated prematurely due to elevated mTORC1 activity in oocytes. This results in depletion of follicles in early adulthood, causing premature ovarian failure (POF). Our results suggest that the Tsc1-Tsc2 complex mediated suppression of mTORC1 activity is indispensable for maintenance of the dormancy of primordial follicles, thus preserving the follicular pool, and that mTORC1 activity in oocytes promotes follicular activation. Our results also indicate that deregulation of Tsc/mTOR signaling in oocytes may cause pathological conditions of the ovary such as infertility and POF.
AB - To maintain the length of reproductive life in a woman, it is essential that most of her ovarian primordial follicles are maintained in a quiescent state to provide a continuous supply of oocytes. However, our understanding of the molecular mechanisms that control the quiescence and activation of primordial follicles is still in its infancy. In this study, we provide some genetic evidence to show that the tumor suppressor tuberous sclerosis complex 2 (Tsc2), which negatively regulates mammalian target of rapamycin complex 1 (mTORC1), functions in oocytes to maintain the dormancy of primordial follicles. In mutant mice lacking the Tsc2 gene in oocytes, the pool of primordial follicles is activated prematurely due to elevated mTORC1 activity in oocytes. This results in depletion of follicles in early adulthood, causing premature ovarian failure (POF). Our results suggest that the Tsc1-Tsc2 complex mediated suppression of mTORC1 activity is indispensable for maintenance of the dormancy of primordial follicles, thus preserving the follicular pool, and that mTORC1 activity in oocytes promotes follicular activation. Our results also indicate that deregulation of Tsc/mTOR signaling in oocytes may cause pathological conditions of the ovary such as infertility and POF.
KW - Follicular activation
KW - Oocytes
KW - Premature ovarian failure
KW - Tsc/mTOR signaling
UR - http://www.scopus.com/inward/record.url?scp=74049132482&partnerID=8YFLogxK
U2 - 10.1093/molehr/gap092
DO - 10.1093/molehr/gap092
M3 - Article
C2 - 19843635
AN - SCOPUS:74049132482
SN - 1360-9947
VL - 15
SP - 765
EP - 770
JO - Molecular Human Reproduction
JF - Molecular Human Reproduction
IS - 12
ER -