난포성장에서의 에스트로겐 수용체1의 역할
- Alternative Title
- Role of estrogen receptor alpha(ERa) in the folliculogenesis
- Abstract
- Estrogen receptor alpha (ERα, Esr1) is expressed in hypothalamus, pituitary and ovary. The importance of Esr1 in hypothalamus and pituitary has been well explained in the neuron- and pituitary-specific Esr1 knockout mice. Esr1 is mainly expressed in the theca/interstitial cells and germinal epithelium. Thus it is believed to mediate the E2 action in these cells, but the functional role of Esr1 in the ovary is not well known. Total Esr1KO mice have a limit action to explore the role of Esr1 mediated E2 in the theca/interstitial cells and germinal epithelium. Therefore Cre-LoxP approach was employed to delete the Esr1 gene in the theca cells, and specifically the reproductive consequence of the deletion was analyzed. Adolescent theca-specific Esr1 knockout (thEsr1KO) mice (< 4 months of age) keep fertility and exhibit normal estrous cycle. However, after 4 month they began to display erratic patterns of estrous cycles and became infertile before they reach the age of 6 months. The ovaries of thEsr1KOmice (≥ 4 months) have much less number of corpora lutea compared with the wild type mice. The number of Cyp17 positive cells was largely increased in the interstitium of the thEsr1KO mouse ovary. Interestingly, basal levels of serum testosterone and FSH were mildly elevated, LH level was markedly lower than that of wild type in age-dependent manner. The superovulation induction using exogenous gonadotropins, resulted in the development of multiple hemorrhagic cysts in thEsr1KO mice and significantly decreased the number of ovulated oocytes. Also the litter size decreased. Taken together, these data demonstrate that theca ESr1 plays a critical role in regulating follicle growth and ovulation. In addition, Esr1 and E2 may control the blood supply in the graafian follicle.
- Issued Date
- 2011
- Awarded Date
- 2001-04
- Type
- Dissertation
- Affiliation
- 성신여자대학교
- Department
- 일반대학원 생물학과
- Table Of Contents
- Contents
I. List of Tables …………………………………………………………………… ii
II. List of Figures …………………………………………………………… iii
III. Background ………………………………………………………………………………… 1
IV.CHAPTER I Characterization of Fertility in Theca-
specific Esr1Knockout Mice…………………………… 7
V. CHAPTER II Insulin-like 3 (INSL3) Inhibit Ovulations through
Theca Cell Proliferation……………………………… 44
VI. CHAPTER III Follicle Antral Growth and Regulationby AQP9 … 75
VII.References …………………………………………………………102
IX. Abstract in Korean ……………………………………………………… 120
X. Acknowledgements …………………………………………………………123
I. List of tables
Table 1-1 Effect of theca-specific Esr1 deletion on fertility………… 23
Table 2-1 Primers for realtime-PCR of INSL3 and its receptor……… 52
Table 3-1 Primers for PCR and siRNA information………………………83
Table 3-2 Decrease of the number of ovulated oocyte by AQP9 siRNA
………………………………………………………………………93
II. List of Figures
Chapter I
Figure 1-1 Genetic information of thEsr1KOmice……………………15-16
Figure 1-2 Patterns of estrous cycles and ovarian histology of WT (Esr1
flox/flox), Esr1 and thEsr1KO mice …………………24-25
Figure 1-3 Superovulation induction in thEsr1 KO mice ……………27-28
Figure 1-4 Blood hormone levels and immunohictochemistry localization
of LH in pituitary of thEsr1KO mice……………………… 29-30
Figure 1-5 Expression of steroidogenic enzyme gene mRNAs after super-
ovulation induction in thEsr1KO mice……………………………31
Figure 1-6 Change the levels of testosterone in serum and ovary during
superovulation induction in thEsr1KO mice………………… 32
Figure 1-7 Distribution of CYP17-positive ells in ovary during super-
ovulation induction in thEsr1KO mice ………………………33-34
Chapter II
Figure 2-1 Map and construct of Rxfp2 lentiviral vector ………………56
Figure 2-2 Diagram of transplantation of osmotic pump ………………57
Figure 2-3 Immunohistological analysis of INSL3 and Rxfp2……… 59-60
Figure 2-4 Expression of INSL3 and Rxfp2 during folliculogenesis…… 63
Figure 2-5 Cloning of 2 type of Rxfp2 receptor in mouse ovary ………64
Figure 2-6 Proliferation of theca cell during primary culture ………65-66
Figure 2-7 Decrease of the number of ovulated COC………………… 67
Figure 2-8 INSL3 caused the theca cell proliferation and morphological
change of theca Decrease of the number of ovulated COC…………………………………………………………… 68
Figure 2-9 Increased the thickness of theca layers after INSL3 treatment
during superovulation …………………………………………… 69
Chapter III
Figure 3-1 Schematic diagram of in vitro follicle culture. ……………82
Figure 3-2 Follicle culture and ovulation……………………………… 86-87
Figure 3-3 Toxicity of siRNA of AQP9 ………………………………………90
Figure 3-4 Suppression of AQP9 expression by AQP9 siRNA ………… 91
Figure 3-5 AQP9 siRNA blocked the follicle growth …………………… 92
Figure 3-6 AQP9 siRNA did not change the expression levels of Ptgs2,
lhcgr andTIMP1……………………………………………………94
Figure 3-7 Profile of AQPs mRNA levels during follicle culture………… 95
- Degree
- Doctor
- Publisher
- 성신여자대학교
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