Corpus luteum is a temporary endocrine organ that is formed and regressed during the female reproductive cycle.It is developed from the residual follicular tissue after ovulation,which is associated with the rapid angiogenesis.Vascular endothelial growth factor(VEGF)is the most important stimulatory factor that regulates the luteal angiogenesis and also plays a key role during corpus luteum formation.VEGF is regulated by hypoxia-inducible factor(HIF)-1,which is a heterodimeric transcription factor consistent of HIF-1α and HIF-1β.The local hypoxia of ovary due to the ruptured follicle and the lack of new vascular networks induces HIF-1α expression and participates in the luteal formation through VEGF-dependent angiogenesis.The present article describes the functional and structural changes during the luteal formation from the local and hypoxic conditions immediately before and after ovulation,with an attempt to clarify the roles of hypoxia in luteal formation as well as ovarian physiology.
Corpus Luteum ; Female ; Humans ; Hypoxia ; Neovascularization, Physiologic ; Ovary ; Vascular Endothelial Growth Factor A

The protein expression of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl(-) channel, in ovarian stimulated premature female rat ovary during a cycle of follicle development and corpus luteum formation was investigated. Animals were injected with 10 U pregnant Mare's serum gonadotropin (PMSG) and subsequently 10 U hCG 48 h later. Time-dependent immunohistochemistry and Western blotting experiments were performed before and 24, 48, 72 h after hCG treatment. The immunohistochemistry revealed that administration of PMSG stimulated the CFTR expression in thecal cell layer and granulosa cell layer of mature follicles 48 h post injection, coincident with the PMSG-induced peak in follicular estradiol. However, the expression of CFTR in the granulose lutein cell layer and thecal lutein cell layer was time-dependently reduced following hCG injection, in accordance with the gradually increased progestogen level during luteum corpus formation. Western blotting analysis demonstrated that rat ovarian tissue expressed the special CFTR band at 170 kD. It is concluded that cAMP-dependent Cl(-) channels are involved in regulation of follicle development and luteum formation.
Connective Tissue Growth Factor/genetics ; Connective Tissue Growth Factor/*metabolism ; Connective Tissue Growth Factor/*physiology ; Corpus Luteum/growth & development ; Ovarian Follicle/growth & development ; Ovary/*metabolism ; Rats, Wistar

OBJECTIVE: The ovarian cycle is characterized by repeating patterns of cellular proliferation and differentiation that accompany follicular development and the formation and regression of the corpus luteum (CL). That angiogenesis may play an important role in this process. Angiogenesis is supposed to be regulated by vascular endothelial growth factor (VEGF). The goal of the present investigation, therefore, was to determine whether the expression of VEGF was changed in the normally cycling human ovary. We also investigated VEGF expression in the regressed CL (ie, nonfunctiong CL) of normal term pregnancy to define the association with steroidogenic activity. To our knowledge there is no report available on VEGF expression in the CL of term pregnancy. METHODS: We assessed VEGF expression in ovaries obtained from, 26-42 yr of age, and from patients undergoing hysterectomy and salpingo-oophorectomy for nonendocrinological or nonovarian disorders. Tissue samples from premenopausal women included specimens from follicular (n=4) and luteal (n 4) phases. In addition, we studied ovarian specimens from pregnant women (n=3). Immunohistochemical analysis for VEGF was performed using a rabbit polyclonal antibody directed against human VEGF. RESULTS: These data demonstrate a development-related VEGF expression in the follicle and indirectly show that VEGF expression may be up to the existence of LH-receptor. And also, VEGF was overexpressed in the regressed CL of pregnant women compared with the functioning CL of nonpregnant cycles CONCLUSION: This study suggests that the intensity of VEGF expression is not correlated with steroidogenic activity, although both of them are stimulated by LH.
Cell Proliferation ; Corpus Luteum ; Female ; Humans* ; Hysterectomy ; Menstrual Cycle ; Ovarian Follicle ; Ovary* ; Pregnancy ; Pregnant Women ; Vascular Endothelial Growth Factor A*

AIMThe expression of VEGF in rat ovaries corpus luteum and its expression pattern were observed to investigate the effect of VEGF on luteal formation and regression.

METHODSThe model of immature rat of pseudopregnant was established using pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG), the expression of VEGF in corpus luteum was detected by immunohistochemistry, the levels of VEGF in corpus luteum was measured by ELISA, and the levels of NO in corpus luteum was measured by chemistry assay.

RESULTSVEGF expressed weakly in rat corpus luteum on the day 1, and enhanced gradually from day 3 to day 5, then went up to the peak on the day 7, and maintained to day 9. On the day 11, the expression of VEGF began to decrease. The levels of VEGF were similar to the expression of VEGF. The levels of NO appeared like double wave. The levels increased gradually from day 1 to day 5, and peaked on the day 7, then decreased on the day 9, while lightly increased on the day 11, and showed significant increase and reached the highest on the day 13, then decreased the lowest on the day 15.

CONCLUSIONThere is a intimate temporal relationship between the expression of VEGF and angiogenesis in corpus luteum, VEGF may play a role in luteum formation by improving angiogenesis mediated by NO, NO may play a role in luteum regression as a luteolytic during the late luteal phase.

Animals ; Corpus Luteum ; metabolism ; Female ; Nitric Oxide ; metabolism ; Pseudopregnancy ; metabolism ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVE: We designed this study to understand the physiologic effects and secretory pattern of IGF-I and IGF-II in human serum and changes in expression of IGF-I and IGF-II in human ovarian tissues during menstrual cycle, and to know which one is more important on human ovarian function between IGF-I and IGF-II, related to FSH, LH and estradiol. METHODS: IGF-I, IGF-II, FSH, LH and estradiol levels were measured in 80 serum samples by ELISA from normal reproductive women. We also examined the immunohistochemical staining of the IGF-I and IGF-II in the ovarian tissues of 14 normal reproductive women. The mean age was 35.6+/-9.15 years-old, ranged from 20 to 45. The average menstrual cycle was 27 to 29 days. RESULTS: 1. The average serum concentration of IGF-I was 204.43+/-50.92 ng/mL, and that of IGF-II was 1381.56+/-292.56 ng/mL. 2. The regular pattern or relationship on serum IGF-I and IGF-II concentrations were not observed (P=0.19). 3. To cross-correlation of serum concentrations of FSH, LH, estradiol and IGF-I, IGF-II, IGF-II was thought to effect on human ovarian menstrual cycles, affected by action of FSH (P=0.048). 4. In the normal reproductive ovaries, we observed immunohistochemical staining for IGF-I in primary, secondary, mature follicle, corpus luteum and stroma, but not in corpus albicans. 5. In the normal reproductive ovaries, we observed immunohistochemical staining for IGF-II in primary, secondary, mature follicle, and corpus luteum but not in corpus albicans and stroma. 6. Stronger immunohistochemical staining was observed in ovaries for IGF-II, rather than IGF-I. CONCLUSION: IGF-I and IGF-II were produced by ovarian tissues, and participated in ovarian folliculogenesis according to menstrual cycles by paracrine, autocrine functions. IGF-II, rather than IGF-I, was thought to effect greater on human ovarian menstrual cycles, affected by action of FSH.
Corpus Luteum ; Enzyme-Linked Immunosorbent Assay ; Estradiol ; Female ; Humans ; Immunohistochemistry ; Insulin-Like Growth Factor I* ; Insulin-Like Growth Factor II ; Menstrual Cycle* ; Ovarian Follicle ; Ovary

OBJECTIVE: Several aspects of female reproduction, from folliculogenesis to corpus luteum function, are related to angiogenesis. The purpose of this study is to measure the concentrations of vascular endothelial growth factor (VEGF) in follicular fluid and serum in patients during In Vitro Fertilization-Embryo Transfer (IVF-ET) cycles. METHODS: In our prospective study, twenty-nine patients who underwent in vitro fertilization by GnRH agonist short protocol were assessed at the our infertility clinic from Aug. 2003 to July 2005. Serum VEGF and follicular fluid VEGF levels were measured in all patients at the time of oocytes retrieval. The assay technique used in this study was ELISA for serum and follicular fluid VEGF. RESULTS: Of 29 cycles, 10 cycles were pregnant (34.5%). A positive correlation existed for follicular fluid VEGF and chronologic age (r=0.428, p-value=0.021). Follicular fluid VEGF concentration showed an inverse relationship with the total number of oocytes retrieved and follicles (r=-0.493, p-value=0.007; r=-0.474, p-value=0.009). But there was no statistically significant relationship between follicular fluid VEGF concentration and serum VEGF concentration (rho=0.347). Follicular fluid VEGF concentration was significantly higher in the non-pregnant group (1468.38+/-727.33 pg/mL) compared to the pregnant group (676.48+/-542.07 pg/mL) (p-value=0.003). CONCLUSION: Our data provide some of the evidences that elevated VEGF concentrations in the follicular fluid are associated with poor conception rates in the IVF-ET cycles.
Corpus Luteum ; Enzyme-Linked Immunosorbent Assay ; Female ; Fertilization ; Fertilization in Vitro ; Follicular Fluid* ; Gonadotropin-Releasing Hormone ; Humans ; Infertility ; Oocytes ; Prospective Studies ; Reproduction ; Vascular Endothelial Growth Factor A*

Ovary is one of the organs in which angiogenesis occurs during ovarian cycle. Angiogenesis is associated with angiogenic factor like acidic fibroblast growth factor, basic fibroblast growth factor and transformation growth factor. Therefore, we performed this study to identify the distribution and mRNA expression of angiogenin, new potential angiogenic factor, in ovary of Korean native cattle by immunohistochemistry and in situ hybridization. Angiogenin immunoreactivity and mRNA expression were observed in endothelial cells, fibroblast and vascular smooth muscle cells. However, we could not observed angiogenin immunoreactivity and mRNA expression in primordial ovarian follicle. In follicular epithelial cells of primary ovarian follicle, weak angiogenin immunoreactivity and mRNA expression were observed. Follicular epithelial cells, theca interna and externa in secondary ovarian follicles, showed angiogenin immunoreactivity, while follicular epithelial cells did the weak mRNA expression. Angiogenin immunoreactivity and mRNA expression were observed in follicular epithlial cells, theca interna and oocyte in tertiary ovarian follicle. The corpus luteum showed strong immunoreactivity and mRNA expression but atretic follicle weak. However, these angiogenin immunoreactivity and mRNA expression became to be weaker during regression. These results suggest that angiogenin may play a role as not only an angiogenic factor but a growth factor in ovary.
Angiogenesis Inducing Agents ; Animals ; Cattle ; Corpus Luteum ; Endothelial Cells ; Epithelial Cells ; Female ; Fibroblast Growth Factor 1 ; Fibroblast Growth Factor 2 ; Fibroblasts ; Immunohistochemistry ; In Situ Hybridization ; Menstrual Cycle ; Muscle, Smooth, Vascular ; Oocytes ; Ovarian Follicle ; Ovary* ; RNA, Messenger* ; Theca Cells

The present study aimed to investigate the role of platelet-activating factor (PAF) in progesterone synthesis and vascular endothelial growth factor (VEGF) expression in rat luteal cells. Immature (25-28 days old) female Sprague-Dawley rats were injected subcutaneously with 50 IU pregnant mare serum gonadotrophin (PMSG), and 25 IU human chorionic gonadotrophin (hCG) 48 h later, to induce follicular development and luteum formation. On day 6 after hCG administration (the day of hCG administration was the first day), the rats were killed by guillotine and the ovarian luteal cells were collected. After incubation for 24 h, luteal cells were incubated without or with different doses (0.1 μg/mL, 1 μg/mL, 10 μg/mL) of PAF at 37 °C (5% CO(2)) for 24 h, and then progesterone concentration was evaluated by radioimmunoassay (RIA); apoptotic rate and VEGF mRNA expression in luteal cells were assessed by flow cytometry and RT-PCR, respectively. The results showed that PAF promoted progesterone production, with a maximal effect at 1 μg/mL (P<0.05); PAF increased apoptotic rate but not in a dose-dependent manner, and 10 μg/mL PAF enhanced apoptotic rate significantly (P<0.05); furthermore, PAF stimulated VEGF mRNA expression in luteal cells, especially at 1 μg/mL (P<0.01). It is suggested that PAF regulates progesterone synthesis and VEGF mRNA expression in luteal cells to mediate corpus luteum formation in rat ovary.
Animals ; Chorionic Gonadotropin ; pharmacology ; Corpus Luteum ; drug effects ; Female ; Luteal Cells ; drug effects ; metabolism ; Platelet Activating Factor ; pharmacology ; Pregnancy ; Progesterone ; biosynthesis ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; metabolism