Establishment of Effective Mouse Model of Premature Ovarian Failure Considering Treatment Duration of Anticancer Drugs and Natural Recovery Time

OBJECTIVES: This study was aimed to establish the most effective premature ovarian failure (POF) mouse model using Cyclophosphamide (CTX), busulfan (Bu), and cisplatin considering treatment duration of anticancer drugs and natural recovery time. METHODS: POF was induced by intraperitoneally injecting CTX (120 mg/kg)/Bu (12 mg/kg) for 1 to 4 weeks or cisplatin (2 mg/kg) for 3 to 14 days to C57BL/6 female mice aged 6 to 8 weeks. Controls were injected with equal volume of saline for the same periods. Body weight was measured every week, and ovarian and uterine weights were measured after the last injection of anticancer drug. To assess ovarian function, POF-induced mice were superovulated with pregnant mare serum gonadotropin and human chorionic gonadotropin, and then mated with male. After 18 hours, zygotes were retrieved and cultured for 4 days. Finally, the mice were left untreated for a period of times after the final injection of anticancer drug, and the time for natural recovery of ovarian function was evaluated. RESULTS: After 2 weeks of CTX/Bu injection, ovarian and uterine weights, and ovarian function were decreased sharply. Cisplatin treatment for 10 days resulted in a significant decrease in ovarian and uterine weight, and ovarian function. When POF was induced for at least 2 weeks for CTX/Bu and for at least 10 days for cisplatin, ovarian function did not recover naturally for 2 weeks and 1 week, respectively. CONCLUSIONS: These results suggest that CTX/Bu should be treated for at least 2 weeks and cisplatin for at least 10 days to establish the most effective primary ovarian insufficiency mouse model.

Effects of three-area laser-assisted zona thinning in 8-cell human embryos on pregnancy outcomes in vitro fertilization / 대한생식의학회지

OBJECTIVE: This study conducted a preliminary examination of the effects of three-area laser-assisted zona thinning (LAZT) during the cleavage stage of embryo development on the hatching process in human in vitro fertilization-embryo transfer (IVF-ET) with subjects of advanced female age or frozen-thawed (FT) embryos. METHODS: Eight-cell stage embryos were treated with LAZT in three areas of the zona pellucida at 120° intervals. The control group was embryos without LAZT. Of the 72 consecutive fresh cycles and the 28 FT embryo transfer cycles, the patients in 55 fresh cycles and 17 FT cycles declined LAZT, and those cycles were defined as the control group. RESULTS: In the fresh cycles, the pregnancy rates were similar in the LAZT and control groups. However, in the FT cycles, the pregnancy rate was significantly higher in the LAZT group than in the control group (45.5% in the LAZT group vs. 23.5% in the control group, p < 0.05). CONCLUSION: These results show that multi-area LAZT resulted in significantly improved pregnancy outcomes in human 8-cell embryos compared to controls.

A Rare Case of an Autoamputated Ovary with Mature Cystic Teratoma

Autoamputated ovary with mature cystic teratoma (MCT) is a rarely reported gynecologic entity with an unknown prevalence. A 34-year-old woman referred to our clinic for presumed left ovarian tumor. Pelvic examination, ultrasonography and computed tomography scan revealed a 5-cm, cystic ovarian mass with calcification and fat component, and tumor markers were as follows, cancer antigen (CA) 125; 10.4 U/mL, CA19-9; 2 U/mL. Laparoscopy was performed. The mass was identified in the left adnexal region without any ligamentous or direct connection with the pelvic organs. The right ovary was normal. However, the left ovary and the tube could not be identified in its proper anatomical location. The mass was successfully removed with sharp and blunt dissection. A review of histopathologic study revealed a MCT. The patient became pregnant within seven months and gave birth to a healthy baby by cesarean section. We present a rare case of an autoamputated ovary with MCT.

Lymphoepithelioma-like carcinoma of the uterine cervix

Lymphoepithelioma-like carcinoma (LELC) of the uterine cervix is exceedingly uncommon. We herein report a rare case of cervical LELC. A 45-year-old woman was admitted to gynecology department with vaginal bleeding for one month. Liquid-based cytology revealed atypical endometrial cells, not otherwise specified on her cervix. On a hysteroscopy, an endocervical mass was identified and the pathologic result was consistent with poorly differentiated squamous cell carcinoma. Magnetic resonance imaging and positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography revealed a 3.1-cm endocervical mass without distant metastasis or enlarged lymph nodes. The International Federation of Gynecology and Obstetrics stage was IB1. A radical hysterectomy and bilateral pelvic lymph node dissection were performed. The pathologic diagnosis was a poorly differentiated carcinoma, showing features of LELC. She has been followed for 8 months without adjuvant treatment since the surgery, during which time there has been no evidence of tumor recurrence or metastasis.

Non-puerperal Uterine Inversion Presented with Hypovolemic Shock

We report a non-puerperal uterine inversion with nulliparous women caused by huge pedunculated submucosal fibroid. Massive bleeding from protruding mass through vagina brought the heart to stop in 42-year-old nulliparous woman. She became cardiopulmonary resuscitation survivor in emergency room and then underwent laparotomy which ended in successful myomectomy rather than hysterectomy considering her demand for future fertility. Meticulous and adequate fluid therapy and transfusion was also administered to recover from hypovolemic status. Pathologic report confirmed benign submucosal fibroid with degeneration, necrosis and abscess formation. Thus, clinician should be aware of uterine inversion when encountered with huge protruding vaginal mass and consider uterus-preserving management as surgical option when the future fertility is concerned.

Mitochondrial Channel Opener Diazoxide Attenuates Hypoxia-Induced sFlt-1 Release in Human Choriocarcinoma Cells

OBJECTIVES: To examine the effect of diazoxide on hypoxia-induced soluble fms-like tyrosin kinase-1 (sFlt-1) release in JEG-3 choriocarcinoma cells. METHODS: Cells were cultured under normoxia (20% O2) or hypoxia (1% O2), and expression of sFlt-1 mRNA and protein release was determined by quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) assays and enzyme-linked immunosorbent assay (ELISA). RESULTS: Tumor necrosis factor-alpha (TNF-alpha) as well as hypoxia stimulated sFlt-1 release and diazoxide inhibited both of them. The selective inhibitor of mitochondrial adenosine triphosphat (ATP)-sensitive K+ channel opener (K(ATP)) 5-hydroxydecanoate (5-HD) completely reversed the diazoxide-induced inhibition of hypoxia-stimulated sFlt-1 release. qRT-PCR and Western blot analyses showed that diazoxide up-regulated the heme oxygenase-1 (HO-1) expression. In addition, the HO-1 inducer cobalt protoporphyrin (CoPP) and the metabolic product of HO-1 bilirubin mimicked diazoxide to inhibit sFlt-1 release and reactive oxygen species (ROS) production under hypoxia, whereas the HO-1 inhibitor zinc protoporphyrin IX (ZnPP IX) antagonized the effect of diazoxide. In cells transfected with the HO-1 siRNA, diazoxide did not exert any effect on sFlt-1 release and ROS production under hypoxia. CONCLUSION: These results, taken together, strongly suggest that up-regulation of the HO-1 expression is the crucial mechanism responsible for the diazoxide-induced inhibition of the sFlt-1 release and ROS production under hypoxia.

Sildenafil Inhibits Advanced Glycation End Products-induced sFlt-1 Release Through Upregulation of Heme Oxygenase-1

OBJECTIVES: We examined the effect of sildenafil citrate on advanced glycation end products (AGEs)-induced soluble fms-like tyrosine kinase 1 (sFlt-1) release in JEG-3 choriocarcinoma cells. METHODS: Cells were incubated with control bovine serum albumin (BSA) or AGEs-BSA, and expression of sFlt-1 mRNA and protein release was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. AGEs-BSA increased sFlt-1 mRNA expression and protein release in a dose-dependent manner. RESULTS: Sildenafil citrate suppressed sFlt-1 mRNA expression and protein release in cells treated with AGEs-BSA in a dose-dependent manner. Likewise, it inhibited the increase of reactive oxygen species (ROS) production and NF-kappaB activity in these cells. Cobalt protoporphyrin (CoPP) and bilirubin also inhibited sFlt-1 release and ROS production in cells treated with AGEs-BSA, whereas zinc protoporphyrin IX (ZnPP IX) antagonized the effect of sildenafil citrate. In cells transfected with the heme oxygenase-1 (HO-1) siRNA, sildenafil citrate failed to inhibit the sFlt-1 release and ROS production. CONCLUSION: These results strongly suggest that sildenafil citrate inhibits sFlt-1 release and ROS production in cells treated with AGEs-BSA through upregulation of the HO-1 expression in JEG-3 cells.

A Case of Vaginal Cancer with Uterine Prolapse

Primary vaginal cancer combined with uterine prolapse is very rare. We present a case of 80-year-old postmenopausal women complaints of something coming out per vagina for the past 20 years, along with blood stained discharge, foul odor leukorrhea, and severe pelvic pain for the last 3 months. A 4 x 5 cm ulcer was present on middle third of vaginal wall with marked edema and ulceration of surrounding tissue. The prolapse was reduced under intravenous sedation in operating room. On gynecologic examination, uterus was normal in size, no adnexal mass was examined, and both parametrium were thickened. Papanicolaou smear was normal. Biopsy of the ulcer at vaginal wall revealed invasive squamous cell carcinoma of vagina. Magnetic Resonance Imaging of abdomen and pelvis showed left hydronephrosis and liver metastasis. Positron emission tomography (PET)/computed tomography (CT) revealed metastasis to lung, liver and iliac bone. She died from progression of disease one month after diagnosis.

A Case of Torsion of a Subserosal Leiomyoma

Uterine leiomyoma is one of the most common gynecological tumor, whereas acute torsion of the uterine leiomyoma is very rare. We report a case of subserosal leiomyoma that was first detected by ultrasonography, and further confirmed as torsion of subserosal leiomyoma by laparoscopic surgery.

A Case of Adenoid Basal Carcinoma of the Uterine Cervix

Adenoid basal carcinoma of the uterine cervix is uncommon neoplasia mostly occurring in postmenopausal women. It has excellent prognosis and a favorable clinical course. In addition, adenoid basal carcinoma is differentiated from adenoid cystic carcinoma by histologic and cellular morphologies, and immunohistochemistry. In this paper, we present the case of a 22 year old Korean female. She initially had a high-grade squamous intraepithelial lesion (HSIL) on Pap smear and a subsequent cervical loop electrosurgical excision procedure (LEEP) specimen revealing adenoid basal carcinoma. The lesion showed the histologic characteristics of adenoid basal carcinoma. Because of the lesion's low potential for recurrence and metastasis, the young primipara had a conization procedure performed and has been under close observation.

The Clinical Experience of an Ultrasound-guided Vacuum-assisted Resection (Mammotome) for Benign Breast Lesions through a Core Needle Biopsy / 대한폐경학회지

OBJECTIVES: This study was performed to consider the clinical experience of an ultrasound-guided vacuum-assisted resection (Mammotome) for benign breast lesions through a core needle biopsy. METHODS: The authors carried out a core needle biopsy and Mammotome for 347 patients and investigated the pathologic results. RESULTS: The significant difference of core needle biopsy and Mammotome results was demonstrated, Spearman correlation coefficient is 0.413 in a correlation analysis. CONCLUSION: This experience suggest Mammotome is a useful procedure for providing more correct pathologic findings through complete resection of benign breast lesions.

Effects of simvastatin on the proliferation and apoptosis of human endometrial stromal cells from women with endometriosis / 대한산부인과학회지

OBJECTIVE: To evaluate the effects of simvastatin on the proliferation and apoptosis of human endometrial cells from women with endometriosis. METHODS: Endometrial tissues were obtained from four women with endometriosis. The endometrial stromal cells isolated from tissue were cultured with 0, 2 and 10 micrometer simvastatin treatments for 48 hours. The proliferation of endometrial stromal cells was inhibited with 2 and 10 micrometer simvastatin treatments compared to control. The effect of simvastatin on the sub-G1 phase of cell cycle was determined by flow cytometry. The expression of apoptosis related molecule (Bcl-2, Bax and caspase-3) was examined in control and simvastatin treatments using western blot. RESULTS: The sub-G1 phase was higher in 10 micrometer simvastatin than in control and 2 micrometer simvastatin (P<0.05). This result showed that simvastatin could induce apoptosis of stromal cells. The expression of Bcl-2 was increased in simvastatin treatments slightly (P<0.05) and the expression of Bax was not different between control and experimental groups. The activation of caspase-3 was significantly higher in 10 micrometer simvastatin treated group than control and 2 micrometer simvastatin treated groups (P<0.05). CONCLUSION: Simvastatin induces apoptosis of endometrial stromal cells and inhibits their proliferation. It was considered that simvastatin could potentially be a therapeutic agent for the treatment of endometriosis.

The effects of leptin on in vitro development of mouse embryos / 대한산부인과학회지

OBJECTIVE: To investigate the effects of leptin on in vitro development of mouse embryos. METHODS: Female C57BL mice, aged 8 to 15 weeks, were superovulated with IP injection of 5 IU of PMSG followed by 5 IU hCG at 48 hours later. And then the mice were mated with male mice. The next morning, one-cell embryos were collected and cultured in media added with various concentrations (0, 5, 50, 500 ng/mL) of leptin for 4 days. In addition, to determine whether the sensitivity to leptin varied at different stages of development, embryos at 2- or 4-cell stage were treated with the same concentrations of leptin and cultured up to blastocyst stage. The total cell number of blastocyst was assessed and the expression of leptin receptor was examined in all stages of development by immnuofluorescence. RESULTS: The rate of blastocyst formation from one-cell embryos significantly increased at culture media that leptin was added at 50 ng/mL concentration, whereas decreased at 500 ng/mL concentration compared to the control (P<0.05). The development rate of embryos, from 2-cell stage, was similar to the rate from 1-cell stage. However, the addition of leptin to culture media in 4-cell embryos had no significant effects on embryo development compared to the control. In addition, the dose-dependent stimulatory or inhibitory effect of leptin on embryo development was weakened at 2-cell and 4-cell embryo stages compared one-cell embryo stage. The total cell number of blastocyst also significantly increased at 50 ng/mL of leptin, but decreased at 500 ng/mL. Leptin receptor was expressed in all stages from one-cell embryos to blastocyst. The intensity of Ob-Rb immnuostaining was mainly stronger in one- or two-cell embryos, decreased with advancing development stages, and increased again in blastocyst. CONCLUSION: This study shows that addition of leptin to embryo culture media affects embryo development in a dose-dependent and developmental stage-dependent manner. The effects of leptin seems to be associated with the expression pattern of leptin receptor at different stages of development.

Localization of aquaporin-3 in mouse placenta and its role / 대한산부인과학회지

OBJECTIVE: Aquaporin (AQP) 3 is a small integral membrane protein that functions as a facilitated transporter of water and glycerol. To elucidate a role of AQP3 in placenta, changes in amniotic fluid composition and fetal growth were investigated using AQP3 null mice. METHODS: Embryonic day 14,5 gestational sacs of wild-type and AQP3 kncok-out pregnant mice, thirty each, were used for this study. AQP3 localization and expression were assessed by immunohistochemistry and western blot. RESULTS: AQP3 was highly expressed in basolateral membrane of visceral yolk sac cells of fetal membrane and syncytiotrophoblast cells of labyrinthine placenta. In contrast, AQP1 was expressed in apical membrane of visceral yolk sac cells and endothelial cells lining vasculature. There was no significant difference in normal placentation and differentiation from trophoblast stem cells between wild type and AQP3 null mice. However, AQP3 null mice had increased amount of amniotic fluid per gram of body weight and decreased osmorality of amniotic fluid with low concentrations of ions and solutes in amniotic fluid. In addition, AQP3 null mice pups were smaller than CD1 wild type mice. CONCLUSION: AQP3 plays an important role in amniotic water balance and nutrient supply to developing fetus by facilitating transplacental transport of water and glycerol.

Aggressive angiomyxoma of the vulva in an adolescent girl / 대한산부인과학회지

Aggressive angiomyxomas (AAMs) are rare, benign, but locally aggressive, hypocellular soft tissue neoplasms found in the vulvovaginal region. AAMs are most commonly found in women in their reproductive years. Only about 150 cases of this rare, soft tissue tumor have been reported thus far, most of which are reported from the gynecologic, obstetric, urologic, and pathologic fields. AAMs are considered to be a slow-growing mesenchymal tumor with a locally infiltrative growth pattern. There are only two reports of metastasic disease. We have managed a case of AAM which occurred during adolescence and was pathologically-confirmed.

Aggressive angiomyxoma of the vulva in an adolescent girl / 대한산부인과학회지

Aggressive angiomyxomas (AAMs) are rare, benign, but locally aggressive, hypocellular soft tissue neoplasms found in the vulvovaginal region. AAMs are most commonly found in women in their reproductive years. Only about 150 cases of this rare, soft tissue tumor have been reported thus far, most of which are reported from the gynecologic, obstetric, urologic, and pathologic fields. AAMs are considered to be a slow-growing mesenchymal tumor with a locally infiltrative growth pattern. There are only two reports of metastasic disease. We have managed a case of AAM which occurred during adolescence and was pathologically-confirmed.

A case of inguinal endometriosis in the absence of previous gynecologic surgery / 대한산부인과학회지

Endometriosis is a common gynecologic disease, it occur not only pelvic organ but also anywhere in human body. However inguinal endometriosis is a very rare condition, its incidence is 0.4% of entire endometriosis. Most of inguinal endometriosis are found as inguinal masses in women in 30s and 40s who have history of gynecologic surgery. Majority of the cases are accompanied with pelvic endometriosis. Authors report a case of inguinal endometriosis in patients who has no history of gynecological surgery.

A case of pure uterine lipoma / 대한산부인과학회지

Lipomatous tumors are the most common mesenchymal tumor. But, pure lipoma of the uterus is very rare and only few cases are reported in international literatures. These tumors usually develop in postmenopausal women and symptoms are similar to leiomyoma. We report a case of a pure uterine lipoma in 64-years-old woman presenting with palpable pelvic mass and voiding difficulty in which a preoperative diagnosis was made by magnetic resonance imaging (MRI), then pathologically confirmed after the operation.

Cord blood-derived CD34(+) cells promotes functional recovery in transient middle cerebral artery occlusion model of rat / 대한산부인과학회지

OBJECTIVE: This study was designated to determine the effect of cord blood cell transplantation in ischemic injury model. METHODS: In this study, we administered human umbilical cord blood (hUCB)-derived CD34(+) cells into the lateral ventricle or directly into the striatum and assessed cell migration in mice with cryoinjury and behavioral recovery in rats with transient middle cerebral artery occlusion (MCAo). CD34(+) cells were isolated by magnetic cell sorting using CD34-microbeads and labeled with CM-Dil. RESULTS: When CD34(+) cells were injected into mice brain with cryoinjury, cells were migrated into a injury site after one week of injection. Similarly, injected CD34(+) cells were migrated into the periphery of infarcted area in rats with transient MCAo. When spontaneous activity was measured using a modified neurological severity score (mNSS), it was found that functional recovery was significantly higher when CD34(+) human umbilical cord blood cell (hUCBC) was transplanted 24 hours after stroke compared with phosphate buffered saline (PBS)-injected or CD34(-) transplanted, stroked animals (P<0.05). Although only small portion of transplanted cells were differentiated into neural lineages, CD34(+) hUCBC transplantation increased Brdu incorporation and recruitment of doublecortin (DCX) (+) cells in ischemic boundary zone. CONCLUSION: These results suggest that hUCBC transplantation may be an effective treatment for brain injuries, such as stroke, or neurodegenerative disorders by promoting endogenous repair process of the brain.

A Case of Cushing's Syndrome in Pregnancy Secondary to an Adrenal Cortical Adenoma

Cushing's syndrome in pregnant women is rare and difficult to be diagnosed because of the syndrome's association with oligomenorrhea or amenorrhea and the changes in cortisol metabolism during normal pregnancy. Cushing syndrome in pregnancy is usually confused with complicated pregnancy, such as preeclampsia or gestational diabetes, and its rarity leads to a low degree of clinical suspicion, often delaying diagnosis. We experienced a case of Cushing's syndrome in pregnancy, which had been considered as the severe preeclampsia and gestational diabetes due to uncontrolled hypertension and hyperglycemia. The pregnancy was terminated with an emergency cesarean operation at 30 weeks of gestation because of severe preeclampsia. In consequence of the evaluation about the Cushing's syndrome after delivery, the adrenal cortical adenoma of right adrenal gland was diagnosed and laparoscopic adrenalectomy was performed.