The functional roles of the intra-oocyte phosphatidylinositol 3-kinase (PI3K) signaling in controlling follicular development in mice
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
The key functions of the mammalian ovary are the production of fertilizable oocytes and thesecretion of steroid hormones. At the time of birth the human ovary is composed of basic unitstermed primordial follicles. Primordial follicles are long-lived structures in the ovary and some ofthem last until the woman reaches menopause. However, the intra-oocyte signaling pathways thatactivate primordial follicles and early follicular development are largely unknown.
In this thesis, the functional roles that the phosphatidylinositol 3-kinase (PI3K) signaling pathwayplays in follicular development were investigated. In vivo approaches using genetically modifiedmouse models were used to determine the functions of several members of the PI3K signalingpathway in oocytes and in follicles. The function of Foxo3a, a substrate of Akt, was investigatedby expressing Foxo3a constitutively in oocytes of primary follicles. We found that continuouslyactive Foxo3a in mouse oocytes caused retardation of oocyte growth, resulting in arrest offollicular development. The functions of p27kip1 (p27) were studied using p27-deficient (p27-/-)mice. It was found that p27 suppresses follicle endowment/formation and activation, and that itinduces follicle atresia. The functions of PI3K signaling in oocytes during follicular activationwere also investigated using conditional mutant mice, by disrupting the Pten in oocytes ofprimordial follicles. We found that, all primordial follicles were prematurely activated due toovergrowth of oocytes and these follicles were depleted in young adulthood, causing prematureovarian failure (POF). At the same time, disruption of the Pten from oocytes of primary follicleshad no effect on activation of primordial follicles, and the follicles developed and maturednormally. The results clearly show that the PI3K pathway in the mammalian oocyte plays a keyrole in follicular activation through control of initiation of oocyte growth and folliculardevelopment.
Place, publisher, year, edition, pages
Umeå: Umeå university , 2009. , 51 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1291
oocyte, PI3K signaling, primordial follicle
Obstetrics, Gynecology and Reproductive Medicine
Research subject Developmental Biology
IdentifiersURN: urn:nbn:se:umu:diva-26110ISBN: 978-91-7264-827-2OAI: oai:DiVA.org:umu-26110DiVA: diva2:236712
Distributor:Medicinsk kemi och biofysik, 901 85, Umeå
2009-10-30, KB3A9, KBC building, Umeå, 13:00 (English)
Sahlin, Lena, Dr
Liu, Kui, Dr
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