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PURPOSE : This study aimed to investigate the effect of intraperitoneal administration of activin on the occurrence of endometriosis using a mouse model of endometriosis. METHODS : A mouse model of endometriosis was prepared by intraperitoneally administering endometrial tissue and blood collected from donor mice to C57BL/6J 7-8- week-old recipient mice. A total of 400 μg of activin A was intraperitoneally administered to model mice in the activin group for 5 days. Intraperitoneal endometriotic lesions were confirmed macroscopically and IL-6 and TNF-α levels in washed ascites were measured by ELISA. RESULTS : Endometriotic lesions were observed in all mice. In the activin group, the maximum diameter of endometriotic lesions was significantly larger than that in control group (4.7±1.3 vs 2.9±0.9 mm, p

Objective : We aimed to demonstrate the effect of prolonged hospitalization on fetal growth in cases of threatened preterm labor (TPL). Methods : In this retrospective cohort study, we included women who received prenatal care for TPL but delivered their child after 36 weeks of gestation. These were compared with a control group of healthy pregnant women and fetuses delivered at term. Fetal growth was compared using biparietal diameter, abdominal circumference (AC), femur length, and estimated fetal weight (EFW) assessed using ultrasonography at 18, 26, 30, and 36 weeks of gestation. Neonatal parameters at birth were also compared. Results : In total, we enrolled 228 control women and 114 women with TPL who were treated with hospitalization, including bed rest. The AC at 30 and 36 weeks of gestation and EFW at 36 weeks of gestation were smaller in women treated with bed rest than for normal pregnant women. The mean duration of pregnancy was shorter in the hospitalization group than in the control group. Neonatal weight, length, head circumference, and chest circumference at birth were smaller after prolonged hospitalization for TPL than after normal pregnancy. Conclusion : Prolonged hospitalization for threatened preterm labor is associated with impaired fetal growth, particularly AC.

As the follicular environment transits from being activin dominant to inhibin dominant during folliculogenesis, it is assumed that activin plays an important role in the early stage of follicular growth. We examined the effects of activin on morphological, biochemical and molecular changes in isolated preantral follicles. Preantral follicles were mechanically isolated from 14-day old female C57BL/6 mice. Each follicle was cultured and observed for 14 days using an in vitro follicle culture system containing FSH, FSH + activin A and FSH + inhibin in the culture medium. We subsequently examined FSH receptor (FSH-R) mRNA expression in isolated follicle cultures with or without activin on days 0 and 2. Activin was observed to significantly stimulate follicle enlargement on days 2, 4, 6 and 8, accelerate morphological changes and increase estradiollevels in culture medium on days 4, 12 and 14. In contrast, inhibin did not alter follicular growth. Additionally, activin stimulated the expression of FSH-R mRNA in isolated granulosa cells. It was demonstrated that activin stimulated the growth of preantral follicles, mainly during the early stage of folliculogenesis, by inducing FSH-R expression, in an isolated follicle culture system.

Purpose : The aims of this study were to clarify the effects of lipopolysaccharide (LPS) on the early development of endometriosis and on the production of cytokines and chemokines in the murine peritoneal cavity. Methods : Endometriotic lesions were induced in C57BL/6J adult female mice by intraperitoneal injection of endometrial fragments plus blood or endometrial fragments plus blood with LPS. On day 7, endometriotic lesions were assessed by gross and microscopic evaluations. Time-dependent changes in the secretion of TNF-α, IL-6, and CXCL2/MIP-2 in peritoneal lavage fluid after the intraperitoneal injection of LPS (50 µg/body) were measured by their respective enzyme-linked immunosorbent assays. Results : The areas of endometriotic lesions in the LPS group (10.8±8.6 mm2) were significantly larger than those in the control group (3.1±3.7 mm2). The levels of TNF-α and IL-6 peaked within 2 hours and the level of MIP-2 reached a maximum on day 1 after the injection of LPS. Conclusions : LPS promotes development of the early stages of murine endometriotic lesions.

Few reports have focused on hemodynamics around delivery in pregnant women because of the difficulty of continuous and noninvasive measurement. Electrical cardiometry allows noninvasive continuous monitoring of hemodynamics and has recently been used in non-pregnant subjects. We compared the use of electrical cardiometry versus transthoracic echocardiography in healthy pregnant women and evaluated hemodynamics immediately after vaginal delivery. In Study 1, electrical cardiometry and transthoracic echocardiography were used to measure cardiac output in 20 pregnant women with threatened premature delivery. A significant correlation was found between the two methods, with electrical cardiometry showing the higher cardiac output. In Study 2, heart rate, stroke volume, and cardiac output were continuously measured in 15 women during vaginal delivery up to 2 h postpartum. Cardiac output increased markedly because of an increased heart rate and stroke volume at the time of newborn delivery. The heart rate then immediately returned to baseline, while cardiac output remained elevated for at least 2 h after delivery because of a sustained high stroke volume. Electrical cardiometry was as readily available as transthoracic echocardiography for evaluating hemodynamics and allowed for continuous measurement during labor. High intrapartum cardiac output was sustained for at least 2 h after vaginal delivery.

We aimed to demonstrate that the serum 25-hydroxyvitamin D (25(OH)D) level in maternal and umbilical cord blood has a seasonal variation in Japanese women. The study cohort comprised 256 healthy Japanese women with a singleton pregnancy who delivered after 36 gestational weeks between 2012 and 2015. The season at delivery was categorized for 3 months and recorded as “spring”, “summer”, “autumn” and “winter”. Subjects were divided into four groups according to season. A sample of peripheral venous blood at 35-36 gestational weeks and blood from the umbilical vein at delivery were taken. The mean serum 25(OH)D concentration (ng/mL) in maternal blood for each season (spring, summer, autumn and winter) was 18.0 (±6.7), 17.1 (±5.1), 21.6 (±8.0) and 16.0 (±5.1), whereas that for umbilical cord blood was 8.8 (±3.6), 8.6 (±2.6), 10.7 (±3.5) and 8.6 (±2.1), respectively. The mean serum 25(OH)D concentration of maternal and umbilical cord blood in autumn was higher than that for the other three seasons. In pregnant Japanese women, the mean serum 25(OH)D concentration in maternal and umbilical cord blood was affected by the season of delivery, with both being highest in autumn. Regardless of the season, the maternal serum concentration of 25(OH)D was low in Japan.

Resveratrol, a natural product and peroxisome proliferator-activated receptor (PPAR) agonist, has been reported to exert anti-cancer effects in several tumor models. A previous study by our group reported that prostaglandin J2, a PPARγ ligand, inhibited cell proliferation in a uterine sarcoma cell line. The aim of the present study was to investigate the role of the Wnt signaling pathway in resveratrol-induced apoptosis and inhibition of cell proliferation in the MES-SA human uterine sarcoma cell line. A WST-1 assay demonstrated that resveratrol inhibited cell proliferation in the MES-SA cell line, and flow cytometry revealed that the number of apoptotic cells increased in a resveratrol dose-dependent manner. The mechanisms underlying these effects of resveratrol were speculated to involve the expression of β-catenin and its target gene, c-myc, which were examined using western blot analysis. The results revealed a dose-dependent downregulation of this β-catenin and c-myc. This effect was blunted by a pharmacological inhibitor of glycogen synthase kinase 3β. Therefore, it is likely that resveratrol inhibited the cell proliferation and increased the number of apoptotic cells, at least partially, via the Wnt signaling pathway. The present results suggest that resveratrol is a potential candidate for the treatment of uterine sarcoma.

Purpose: A retrospective, cohort study was conducted between 2009 and 2017 in a private infertility center to determine the predictive value of endogenous estrogen (E2) and progesterone (P4) levels in hormone‐replacement frozen embryo replacement (FER) treatment cycles. Methods: A total of 120 consecutive, infertile patients who became pregnant after FER cycles were analyzed (age: 37.4 ± 4.4 years). Electively vitrified blastocysts were created during natural cycle IVF or mild ovarian stimulation treatments and subsequently transferred through delayed vitrified‐thawed blastocyst transfer cycles supplemented with estrogens and a combination of synthetic progestogens. Serum E2 and progesterone P4 levels were intensively monitored every five days (from the day after embryo transfer until 9w1d of pregnancy) and compared among patients with a subsequent live birth (n = 76) or first‐trimester pregnancy loss (n = 44). Results: Endogenous placental activity started as early as 5‐6th pregnancy week differing significantly according to pregnancy outcome. For P4, the exponential rise from 6w2d onwards allowed distinguishing between failing and successful conceptions. For P4, lower quartiles of the live birth group did not intersect with upper quartiles of the miscarriage group. Conclusions: Innovative FER protocols incorporating synthetic progestogens allow the correct measurement of endogenous placental activity and could help to monitor early first‐trimester ART pregnancies.

Purpose The purpose of this study was to investigate the differences in plasma concentrations of adipokines in pregnant women with varying body mass indices (BMIs) with every trimester. Materials and Method In this study, 89 pregnant women were recruited. These women were divided into lean, normal, and overweight/obese groups. Serum levels of adiponectin, resistin, leptin, and visfatin were measured in the first, second, and third trimesters. Results In the overweight/obese group, adiponectin, resistin, and visfatin concentrations were not significantly affected by advanced gestational age. Leptin concentrations in the third trimester were significantly higher than those in the first and second trimesters. Adiponectin concentrations in the overweight/obese group were significantly lower than those in the lean group in the first and second trimesters. Visfatin concentrations in the overweight/obese group were significantly lower than those in the normal group in the first trimester. Leptin concentrations in the overweight/obese group were significantly higher than those in the lean and normal groups in all trimesters. Conclusion In the first trimester, the largest differences were observed between the overweight/obese group compared to the lean and normal group. The changes in adipokines in overweight/obese groups is different from those in lean and normal groups.

Purpose: To assess the kisspeptin concentrations in follicular fluid and their relationship with clinical outcomes during assisted reproductive technology. Methods: Thirty-nine patients who were aged 24-40 years and underwent oocyte retrieval for in vitro fertilization/intracytoplasmic sperm injection participated in this study. In 65 follicular fluid samples that had been obtained from 30 patients and their blood samples, the kisspeptin levels were measured in order to investigate the correlations with their gonadal hormone levels. Venous blood samples were collected from 14 patients to investigate their plasma kisspeptin levels across different phases of assisted reproductive technology. Results: The follicular fluid kisspeptin level was significantly higher than that of the plasma level and was positively associated with the follicular fluid estradiol concentration and with the serum estradiol and number of mature oocytes. In the plasma, the maximum concentration of kisspeptin was observed on the day of ovum pick-up and on the day of embryo transfer during ovarian stimulation for assisted reproductive technology. Conclusion: Kisspeptin was present in the follicular fluid and the plasma kisspeptin concentration was affected by ovarian stimulation. Kisspeptin appears to affect oocyte maturation and ovulation.

Purpose: It is known that various types of stress in early life increase the incidence of diabetes, myocardial infarctions, and psychiatric disorders in adulthood. We examined the mechanism by which neonatal immune stress reduces sexual behavior in adult male rats. Methods: Male rats were randomly divided into 3 groups: the control (n=17), postnatal day 10 lipopolysaccharide (PND10LPS) (n=31), and PND25LPS (n=16) groups, which received intraperitoneal injections of LPS (100 μg/kg) or saline (injection volume: ≤0.1 ml/g) on postnatal days 10 and 25. In experiment 1, male rats (age: 11 to 12 weeks) were put together with female rats in a one-to-one setting for mating, and sexual behavior (mounting, intromission, and ejaculation) was monitored for 30 minutes. The serum levels of luteinizing hormone (LH) and testosterone (T) and the hypothalamic mRNA expression levels of factors related to sexual behavior were examined. After experiment 1 finished, the remaining 37 male rats were used for experiment 2: the control group (n=8), PND10 LPS group (n=21) and PND25LPS group (n=8) these rats had been given an i.p. injection of the saline during the expriment1. All of the rats were orchidectomized at 14 weeks of age. After a 3 week recovery period, a silastic tube containing crystalline T was subcutaneously implanted into the back of each rat. The rats’ sexual behavior, serum hormone concentrations, and hypothalamic mRNA expression levels were assessed. Results: In experiment 1, preputial separation occurred significantly later in the PND10LPS group than in the control group. The frequency of sexual behavior was significantly lower in the PND10LPS group than in the control group. The serum T concentrations of the PND10LPS and PND25LPS groups were significantly lower than that of the control group, but the serum LH concentrations of the 3 groups did not differ significantly. The hypothalamic mRNA expression levels of progesterone receptor B (PRB) and gonadotropin-releasing hormone (GnRH) were significantly lower in the PND10LPS and PND25LPS groups than in the control group, whereas the hypothalamic PRA+B mRNA expression levels of the 3 groups did not differ significantly. In experiment 2, after T supplementation the frequency of sexual behavior was significantly lower in the PND10LPS and PND25LPS groups than in the control group, although there were no significant differences in the serum T or LH concentrations or the hypothalamic PRB, PRA+B, or GnRH mRNA expression levels of the 3 groups. Conclusion: In male rats, immune stress in the early neonatal period delayed sexual maturation, reduced sexual behavior, suppressed the serum T concentration, and downregulated the hypothalamic mRNA expression levels of GnRH and the PR in adulthood. The delayed sexual maturation was presumed to have been caused by the reduction in the serum T concentration. However, the rats that experienced neonatal stress exhibited reduced sexual behavior irrespective of their serum T concentrations.

Aim: We aimed to evaluate the effect of prolonged hospitalization for threatened preterm labor on maternal and fetal vitamin D status. Methods: This was a retrospective cohort study, spanning 4 years, including 18 women with threatened preterm labor and 36 women with normal pregnancy, who received prenatal care for a singleton pregnancy at our center. Threatened preterm labor cases were women who were admitted to our hospital after the second trimester test, for at least 28 days, during which, the third trimester test was also performed. Controls were randomly sampled from women matched for age as well as the season during which the third trimester test was performed. Serum 25-hydroxyvitamin D concentration in maternal blood was compared between the two groups at second trimester, third trimester and in the umbilical cord blood at delivery. Results: The mean±SD of maternal serum 25-hydroxyvitamin D concentration in the threatened preterm labor group (14.0±3.0 ng/mL) was significantly lower than that in the control group (17.8±5.9 ng/mL) (p

Purpose of investigation: To evaluate the safety and efficacy of loop electrosurgical excision procedure (LEEP) biopsy using a "see-and-treat" strategy, and compare outcomes after "LEEP biopsy, inpatient LEEP and ablation, and inpatient conization with cervical intraepithelial neoplasia (CIN) grade 2/3. Materials and Methods: The authors performed a retrospective study including 300 women with CIN2/3 who were followed up ≥ 6 months following outpatient LEEP/inpatient LEEP and ablation/inpatient conization. Recurrence, additional treatment for recurrence, pregnancy, and term delivery following treatment were evaluated. Results: During the median follow-up duration of 22 months, recurrences were significantly more common following LEEP biopsy (39%) compared to LEEP and ablation (13%) and conization (16%) and were managed by repeat LEEP. Pregnancy and full-term delivery rates following LEEP biopsy were significantly higher. Conclusion: "See-and-treat" LEEP biopsy was safely performed in the outpatient department. Pregnancy rates and full-term deliveries following LEEP biopsy appear favorable.

The effects of androgens on gonadotropin-releasing hormone (GnRH) secretion in females have not been fully established. To clarify the direct effects of androgens on hypothalamic reproductive factors, we evaluated the effects of chronic testosterone administration on hypothalamic GnRH regulatory factors in ovariectomized (OVX) female rats. Both testosterone and estradiol reduced the serum luteinizing hormone levels of OVX female rats, indicating that, as has been found for estrogen, testosterone suppresses GnRH secretion via negative feedback. Similarly, the administration of testosterone or estradiol suppressed the hypothalamic mRNA levels of kisspeptin and neurokinin B, both of which are positive regulators of GnRH, whereas it did not affect the hypothalamic mRNA levels of the kisspeptin receptor or neurokinin 3 receptor. On the contrary, the administration of testosterone, but not estradiol, suppressed the hypothalamic mRNA expression of prodynorphin, which is a negative regulator of GnRH. The administration of testosterone did not alter the rats’ serum estradiol levels, indicating that testosterone’s effects on hypothalamic factors might be induced by its androgenic activity. These findings suggest that as well as estrogen, androgens have negative feedback effects on GnRH in females and that the underlying mechanisms responsible for these effects are similar, but do not completely correspond, to the mechanisms underlying the effects of estrogen on GnRH.