• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2002.11a
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• pp.113-113
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• 2002

The stimulatory effect of EGF and FSH on oocyte maturation have been reported in various mammalian species. And some reports presented FSH enhanced the effect of EGF on oocyte maturation. But, the interaction between EGF and FSH on nuclear maturation of mammalian oocytes is not fully understood. We observed the effect of EGF and FSH on nuclear maturation during in vitro maturation of mouse oocytes. Also, we examined the interaction between EGF and FSH on nuclear maturation of mouse oocytes using the EGFR inhibitor or FSH inhibitor. Germinal vesicle (GV) stage oocytes were obtained from 3-4weeks PMSG primed BCFI hybrid mice and cultured in TCM-199 medium with 0.4%PVP supplemented with/without EGF (1ng/ml), FSH (1ug/ml), EGFR specific tyrosine kinase inhibitors: Tyrphostin AG 1478 (500nM), MAP kinase kinase inhibitor : U0126 (20uM) or PD 98059 (100uM) for 14-l5hr. Rapid staining method were used for the assessment of nuclear maturation. Nuclear maturation rates of EGF indjor FSH-treated group were significantly higher than those of control group. Treatment of EGFR inhibitor significantly block the nuclear maturation of GV oocyte in EGF-treated group, but it did not block those of GV oocyte in FSH-treated or FSH and EGF-treated group. Treatment of FSH inhibitor(U0126, PD98059) significantly block the nuclear maturation of EGF-treated group, FSH-treated and FSH and EGF-treated group. These results show that EGF has a stimulatory effect as well as different action pathway with FSH on in-vitro maturation of mouse oocyte in vitro. Therefore, further studies will be needed to find the signaling pathway of EGF associated with nuclear maturation.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.2
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• pp.186-189
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• 2010

Purpose: As many patients often showed the value of menopause although they were women of childbearing age, this study looked into their previous history. According to the findings, they were patients with a mastectomy due to breast cancer and were taking breast cancer treatment Tamoxifen (the women hormone inhibitor) after chemotherapy. This study is conducted to examine changes in FSH and E2 concentration of patients breast cancer patients of childbearing age according to Tamoxifen used to prevent recurrence of breast cancer and proliferation of mammary parenchyma. Materials and Methods: This study aims to investigate similarity in patients treated with surgery who were in their childbearing age and in values of FSH and E2 by dividing test results of FSH and E2 requested at the department of nuclear medicine among patients who visited this hospital from Jan. 2009 to Mar. 2010 into women of childbearing age (n=50), menopausal women (n=50), and patients with breast cancer surgery who take Tamoxifen (n=50) and then comparing the test results. Results: The FSH and E2 test results of 50 patients were compared and analyzed as average${\pm}$standard deviation, and the results showed that the figure of women of childbearingage (n=50) was FSH : $7.14{\pm}6.19$, E2 : $138.76{\pm}85.40$, that of menopausal women (n=50) was FSH : $52.12{\pm}24.43$, E2 : $15.06{\pm}4.43$, and that of patients with breast cancer surgery who were in their childbearing age (n=50) was FSH : $44.21{\pm}21.07$, E2 : $13.53{\pm}4.26$. When these different results of FSH and E2 were compared, the value of patients with breast cancer surgery who were in their childbearing age with Tamoxifen was somewhat similar to that of menopausal women. Conclusion: The test results of FSH and E2 have reportedly found the test values of patients with breast cancer surgery could be similar to that of menopausal women eventhough they were in their childbearing age due to the women hormone inhibitor Tamoxifen. Therefore, if a tester conducts this experiment after understanding the clinical meaning, the reliability of the tester reporting test results would be increased.

• Animal cells and systems
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• v.16 no.2
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• pp.127-134
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• 2012

We investigated the effects of fadrozol, an aromatase inhibitor (AI), and $17{\alpha}$-methyltestosterone (MT) on the induction of sex change in juvenile longtooth grouper $Epinephelus$ $bruneus$, via histological observation of gonads. Changes in the mRNA expression of GtH subunits (FSH-${\beta}$ and LH-${\beta}$) in the pituitary, and estradiol-$17{\beta}$ (E2) and 11-ketotestosterone (11-KT) levels in the blood were also surveyed after AI and MT treatment. Juvenile longtooth groupers ($113{\pm}17g\;body\;weight$; $16.2{\pm}1.2cm\;body\;length$) received intramuscular injections of AI at 3 (3-AI) and 5 (5-AI) mg/kg BWdoses and MT at a 5 mg/kg BW (5-MT) dose. At week 7 post-injection, 3-AI and 5-MT oocytes were degenerated, and gonads of the 5-AI group initiated spermatogenesis. At week 21 post-injection, 3-AI- and 5-MT-treated gonads contained spermatogonia and spermatocytes, while 5-AI treatment induced advanced stages of spermatogenesis. The serum E2 level showed no significant differences throughout the experimental period, whereas that of 11-KT was significantly elevated in the 5-AI group at weeks 7 and 21 post-injection. A significant increase in the expression of FSH-${\beta}$ mRNA was evident in the 5-AI group at week 21 post-injection. In contrast, LH-${\beta}$ mRNA expression did not significantly differ among groups during the experimental period. These results imply that sex change has two stages in the longtooth grouper. In the first stage, oocytes are degenerated by the stimulation by 11-KT, and in the second stage spermatogenesis occurs, owing to the co-effects of 11-KT and FSH-${\beta}$.

• Korean Journal of Animal Reproduction
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• v.17 no.2
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• pp.165-171
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• 1993

While ornithine decarboxylase (ODC) is considered a key enzyme in the biosynthesis of polyamines, difluoromethylornithine(DFMO) acts as an inhibitor of polyamine synthesis. Cycling crossbred gilts were randomly assigned to one of two (treatment and control) groups (6/group). An indwelling silicone catheter was surgically implanted in the jugular vein of each animal. DFMO was dissolved in saline(200 mg/ml) and adminstered by i. m. injection at a dose of 80 mg/kg/day. The control group received an equivalent volume saline injection. DFMO was injected 3 times daily(08:00. 16:00. 24:00h) from day 16 of estrous cycle to 21 or until estrus. Once daily blood samples (10ml) were taken from day 14 until two days after the last DFMO treatment. Window blood samples were collected every 15 min for 8 h (from 08:00 to 16:00h) starting on day 16 and continuing until day 21 from one gilt per day. Serum progesterone (P$_4$), estradiol (E$_2$), LH and FSH were measured. Typical concentration profiles for P$_4$ and E$_2$ were seen during the follicular phase regardless of DFMO treatment. Injection of DFMO suppressed the preovulatory LH concentration in the serum(p<0.01) while having no effect on FSH profile. The present results indicate that DFMO had an inhibitory effect on LH secretion in the pig, but did not affect PI, E2 or FSH release.

• The Korean Journal of Zoology
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• v.30 no.2
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• pp.117-139
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• 1987

The present experiments were carried out to investigate the mode of cAMP regulation of cumulus expansion in pig. Intracellular level of cAMP in the cumulus cells was modulated by culturing porcine cumulus oocyte complexes (COC's) with forskolin, an adenylate cyclase stimulator and 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor. The role of calcium in the hormone induced cumulus expansion process was also studied. Forskolin in the medium stimulated cumulus expansion from the concentration of 0.01 $\mu$M and induced full expansion at l-10 $\mu$M In contrast, IBMX in the medium (20-180 $\mu$M) failed to induce the expansion. Verapamil, a calcium ion transport blocker, suppressed follicle stimulating hormone(FSH)-induced cumulus expansion in a dose dependent fashion (0.002-0. 2 mM) when the COC's were exposed to the drugs during culture period (32 hr). But verapamil did not interfere with the triggering action of FSH during early four hours of culture period. The data presented here showed that adenylate cyclase in the porcine cumulus cells may play a key role in the regulation of the intracellular cAMP level and calcium ion may be involved in the later period of cumulus expansion process.

• Clinical and Experimental Reproductive Medicine
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• v.35 no.2
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• pp.143-153
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• 2008

Objective: To investigate the effects of aromatase inhibitor on reproductive hormone profiles and evaluate it's ovulation inducing capability in anovulatory infertile women. Methods: We quantified the blood levels of reproductive hormones from 30 healthy normal cycling women in natural cycle (control) and letrozole medicated cycle (study). LH, FSH, estradiol, testosterone, DHEA-S were quantified on third, 11th, 21th day in both cycles, and on 21th day, progesterone was added. Sixth anovulatory infertile women received either letrozole or clomiphene citrate for ovulation induction (n=30 in each groups). We compared the clinical parameters such as ovulation rate, pregnancy rate, the day of LH surge, number of follicles and endometrial thickness, cervical mucus amount, spinnbarkeit, mean diameter of follicles on the day of LH surge. Results: Letrozole had no effect on the LH, FSH, estradiol, DHEA-S secretion but there were significant increase in testosterone level on day 11 and progesterone level on day 21 in letrozole medicated cycle compared than control cycle ($0.40{\pm}0.16$ vs $0.28{\pm}0.11\;ng/ml$, p=0.002, $18.18{\pm}13.07$ vs $8.38{\pm}7.64\;ng/ml$, p=0.001, respectively). In comparison between letrozole and clomiphene groups, there were no significant difference in ovulation rate, pregnancy rate, number of mature follicle, mean diameter of follicles, but showed earlier LH surge, thicker endometrium, more cervical mucus, and higher spinnbarkeit in letrozole group ($12.12{\pm}2.46$ vs $14.52{\pm}3.18$ days, p=0.006, $10.48{\pm}1.23$ vs $8.52{\pm}0.93\;mm$, p=0.000, $2.04{\pm}0.61$ vs $1.57{\pm}0.59$, p=0.012, $6.00{\pm}1.12$ vs $4.95{\pm}1.61\;cm$, p=0.003, respectively). Conclusion: Letrozole may augment folliculogenesis and improve the endometrial condition for implantation in normal cycling women. Ovulation efficacy of letrozole in anovulatory women was comparable to clomiphene citrate and letrozole may be more physiological in ovulation induction.

• The Korean Journal of Zoology
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• v.30 no.1
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• pp.1-9
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• 1987

Cyclic AMP (cAMP) was known to play a key role in the regulation of cumulus expansion and oocyte maturation of mammalian cumulus-oocyte complexes (COC's) in vivo and in vitro. The present experiments were conducted to know how intracellular level of cAMP in these cells is controlled. Intracellular cAMP level was modulated by culturing mouse CGC's with an adenylate cyclase stimulator, forskolin, a phosphodiesterase inhibitor, 3-isobutyl-1-methyixanthine (IBMX), human chorionic gonadotrophin (HCG), or follicle stimulating hormone (FSH). The rate of cumulus expansion and germinal vesicle break-down (GVBD) was checked after culture and used as a biological end point. Forskolin in the medium began to stimulate the expansion of the complexes at 1 nM and induced maximum expansion (80~90%) at 0 1~10 $\mu$M. The expansion rate was reduced to 60% when forskolin concentration was increased to 100 $\mu$M. Oocyte GVBD occurred normally (75~82%) in the presence of 10 $\mu$M of forskolin, but partial suppression was appeared at 100 pM of the drug (40%). IBMX also stimulated the expansion from the concentration of 0.01 pM and induced full expansion (81~89%) between the concentration of 1-1000 $\mu$M. Meiotic resumption was occurred normally under 10 $\mu$M of IBMX, but suppressed drastically from the concentration of 100 $\mu$M. The minimum exposing time to hormone or drugs required to trigger cumulus expansion was two minutes with HCG, 15~30 minutes with FSH and fors kolin, and two hours with IBMX. The data presented here seemed to imply that intracellular cAMP level in cumulus cells is regulated by both adenylate cyclase and phosphodiesterase and cumulus expansion is induced by a peak of cAMP while meiotic arrest is maintained by continuous presence of cAMP.

• Clinical and Experimental Reproductive Medicine
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• v.32 no.1
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• pp.27-32
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• 2005

Objective: To evaluate the effectiveness of aromatase inhibitor (AI) for ovulation induction in polycystic ovary syndrome (PCOS) patients with thin endometrium, hyper-responsiveness after clomiphene citrate (CC) treatment. Material and Methods: A prospective study was performed in 43 PCOS patients (50 cycles) with ovulatory dysfunction between March 2004 and September 2004. AI group (total 36 cycles) included the patients 1) with thin endometrium below 6 mm on hCG day after CC (n=17), 2) with more than 5 ovulatory follicles after 50mg of CC (n=4), 3) who do not want multiple pregnancy (n=14). Patients were treated with Letrozole 2.5mg for days 3 to 7 of the menstrual cycle. CC group (total 14 cycles) were treated with CC 50~100 mg. Results: In PCOS patients, ovulation was occurred 97.2% after AI use. Between AI group and CC group, there was no significant difference in the mean age, duration of infertility, interval of menstruation, basal FSH, prior treatment cycles, and the day of hCG administration. But, the number of mature follicles (${\geq}15mm$) was lower in the AI group ($1.08{\pm}0.45$ vs. $1.64{\pm}0.75$) (p=0.018), and the thickness of endometrium (mm) was significantly thicker in the AI group ($10.35{\pm}1.74$ vs. $9.23{\pm}1.61$) (p=0.044), and E2 (pg/ml) concentration on hCG day was lower in the AI group ($116.9{\pm}75.8$ vs. $479.5{\pm}300.8$) (p=0.001). Among the AI group, patients with prior thin endometrium (below 6 mm) during CC treatment showed $10.6{\pm}1.6mm$ in the endometrial thickness and $106.6{\pm}66.8pg/ml$ in $E_2$ concentration. Patients with more than 5 ovulatory follicles after CC showed decreased follicle number ($1.25{\pm}0.5$) compared to prior CC cycle. Conclusions: In PCOS patients, AI group showed significantly thicker endometrium, lesser number of mature follicles, and lower E2 concentration on hCG day than CC group. AI might be useful alternative treatment for ovulation induction in PCOS patients with thin endometrium and hyper-responsiveness after CC treatment.

• Clinical and Experimental Reproductive Medicine
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• v.36 no.2
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• pp.111-119
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• 2009

Objective: The aim of this study was to compare the clinical efficacy of clomiphene citrate (CC) and letrozole combined with gonadotropins for controlled ovarian stimulation (COS) in patients with CC-induced thin endometrium Methods: Fifty-one intrauterine insemination cycles performed in patients who previously had a thin endometrium (<8 mm) to ovulation induction using CC were included in this study. A CC 100 mg/day (CC+gonadotropin group, n=26) or letrozole 2.5 or 5 mg/day (letrozole+gonadotropin group, n=25) was administered on day 3~7 of the menstrual cycle, combined with gonadotropins at dose 75~150 IU every other day starting on day 5~7. We compared total dose of gonadotropin used, endometrial thickness, endometrial pattern, number of follicles ${\geq}14\;mm$ on hCG day, pregnancy rate and multiple pregnancy rate between the two groups, which were statistically analyzed using Mann-Whitney U test or Fisher's exact test, where appropriate. Results: There were no significant differences in clinical characteristics such as age, duration of infertility, number of previous IUI cycles, basal serum hormone levels and cause of infertility between the two groups. In both groups, the endometrium was significantly thicker than that of previous ovulation induction cycles using CC. No significant differences were found in the total dose of gonadotropin used, day of hCG administration, the rate of triple endometrium and pregnancy rate. The number of follicles ${\geq}14\;mm$ was significantly lower ($3.7{\pm}1.7$ vs. $2.8{\pm}1.7$, p=0.03) and the endometrium on hCG day was significantly thicker ($7.7{\pm}1.5$ vs. $9.1{\pm}1.7$, p=0.001) in letrozole+gonadotropin group compared to CC+gonadotropin group. Conclusion: The clomiphene citrate and letrozole combined with gonadotropins appear to avoid the undesirable effects on the endometrium frequently seen with CC for ovulation induction. However, in terms of adequate endometrial development or optimal follicular growth, letrozole may be more beneficial than CC for gonadotropin-combined COS in patients with CC-induced thin endometrium. Further prospective randomized controlled studies in a larger scale will be necessary to confirm our findings.