Sonographic confirmation of placental detachment during placental delivery for uterine inversion prevention.

AIM: To evaluate the usefulness of transabdominal sonographic confirmation of placental detachment in preventing uterine inversion. METHODS: This was 14-year retrospective cohort study that included women who had transvaginal deliveries in our hospital. We introduced routine transabdominal ultrasonography during placental delivery to prevent uterine inversion. Followed by the confirmation of placental detachment by ultrasonography, we started placental delivery procedure. The frequency of uterine inversion during placental delivery was compared before and after the ultrasonography was introduced. Moreover, the duration of the third stage of labor and bleeding volume during labor were compared between the ultrasonography performing group (USG group) and the non-performing group (non-USG groups). RESULTS: Five thousand and eighty-one women, including 1724 and 3357 women who delivered before and after the ultrasonography was introduced, respectively. The frequency of uterine inversion after the introduction of the ultrasonography system was significantly reduced compared to that before the introduction (0.03% vs. 0.23%, p = 0.03). Even after the introduction of ultrasonography, the actual rate of performing ultrasonography remained 54.1% due to various restrictions. The mean duration of the third stage of labor in the USG group was slightly longer than that in the non-USG group (8.4 ± 5.0 vs. 6.8 ± 3.6, p < 0.01). The mean bleeding volume during labor in the USG group was higher compared with the non-USG group (457 ± 329 vs. 418 ± 285, p < 0.01). CONCLUSIONS: Transabdominal sonographic confirmation of placental detachment may be useful in preventing uterine inversion.

Age-Dependent Changes in the Effects of Androgens on Female Metabolic and Body Weight Regulation Systems in Humans and Laboratory Animals.

In recent years, the effects of androgens on metabolic and body weight regulation systems and their underlying mechanisms have been gradually revealed in females. In women and experimental animals of reproductive age, androgen excess can adversely affect metabolic functioning, appetite, and body weight regulation. In addition, excess androgens can increase the risk of metabolic disorders, such as obesity, insulin resistance, and diabetes. These unfavorable effects of androgens are induced by alterations in the actions of hypothalamic appetite-regulatory factors, reductions in energy expenditure, insulin resistance in skeletal muscle, and ß-cell dysfunction. Interestingly, these unfavorable effects of androgens on metabolic and body-weight regulation systems are neither observed nor evident in ovariectomized animals and post-menopausal women, indicating that the adverse effects of androgens might be dependent on the estrogen milieu. Recent findings may provide novel sex- and age-specific strategies for treating metabolic diseases.

Effects of undernutrition and low energy availability on reproductive functions and their underlying neuroendocrine mechanisms.

It has been well established that undernutrition and low energy availability disturb female reproductive functions in humans and many animal species. These reproductive dysfunctions are mainly caused by alterations of some hypothalamic factors, and consequent reduction of gonadotrophin-releasing hormone (GnRH) secretion. Evidence from literature suggests that increased activity of orexigenic factors and decreased activity of anorexigenic/satiety-related factors in undernourished conditions attenuate GnRH secretion in an integrated manner. Likewise, the activity of kisspeptin neurons, which is a potent stimulator of GnRH, is also reduced in undernourished conditions. In addition, it has been suggested that gonadotrophin-inhibitory hormone, which has anti-GnRH and gonadotrophic effects, may be involved in reproductive dysfunctions under several kinds of stress conditions. It should be remembered that these alterations, i.e., promotion of feeding behavior and temporary suppression of reproductive functions, are induced to prioritize the survival of individual over that of species, and that improvements in metabolic and nutritional conditions should be considered with the highest priority.

Transgender man receiving testosterone treatment became pregnant and delivered a girl: A case report.

Many transgender men receive testosterone therapy to achieve virilization. The therapy is often mistaken for having a contraceptive effect because it causes amenorrhea. However, some treated patients become pregnant, which is not well known. A 25-year-old transgender man who had received testosterone for 3 years had an unplanned pregnancy during discontinuation of treatment. He was unaware of his pregnancy, resumed testosterone, and continued treatment until pregnancy was confirmed. His female child was exposed to androgens during the fetal period; thus, careful, long-term observation was required. He developed insomnia and depression during the postpartum, and giving birth made it difficult for him to change his family register to male. Transgender men can become pregnant through sexual intercourse with biological men, even during hormone replacement therapy, so correct contraception is necessary to avoid unwanted pregnancies. Transgender sex education is important to increase awareness of this issue among individuals and medical professionals.

Neuroendocrine mechanisms of reproductive dysfunctions in undernourished condition.

It is well known that undernourished conditions disturb female reproductive functions in many species, including humans. These alterations are mainly caused by a reduction in gonadotrophin-releasing hormone (GnRH) secretion from the hypothalamus. Evidence from the literature suggests that some hypothalamic factors play pivotal roles in the coordination of reproductive functions and energy homeostasis in response to environmental cues and internal nutritional status. Generally, anorexigenic/satiety-related factors, such as leptin, alpha-melanocyte-stimulating hormone, and proopiomelanocortin, promote GnRH secretion, whereas orexigenic factors, such as neuropeptide Y, agouti-related protein, orexin, and ghrelin, attenuate GnRH secretion. Conversely, gonadotrophin-inhibitory hormone, which exerts anti-GnRH and gonadotrophic effects, promotes feeding behavior in many species. In addition, the activity of kisspeptin, which is a potent stimulator of GnRH, is reduced by undernourished conditions. Under normal nutritional conditions, these factors are coordinated to maintain both feeding behavior and reproductive functions. However, in undernourished conditions their activity levels are markedly altered to promote feeding behavior and temporarily suppress reproductive functions, in order to prioritize the survival of the individual over that of the species.

Changes in Endogenous Oxytocin Levels and the Effects of Exogenous Oxytocin Administration on Body Weight Changes and Food Intake in Polycystic Ovary Syndrome Model Rats.

Polycystic ovary syndrome (PCOS) is frequently seen in females of reproductive age and is associated with metabolic disorders that are exacerbated by obesity. Although body weight reduction programs via diet and lifestyle changes are recommended for modifying reproductive and metabolic phenotypes, the drop-out rate is high. Thus, an efficacious, safe, and continuable treatment method is needed. Recent studies have shown that oxytocin (OT) reduces body weight gain and food intake, and promotes lipolysis in some mammals, including humans (especially obese individuals), without any adverse effects. In the present study, we evaluated the changes in endogenous OT levels, and the effects of acute and chronic OT administration on body weight changes, food intake, and fat mass using novel dihydrotestosterone-induced PCOS model rats. We found that the serum OT level was lower in PCOS model rats than in control rats, whereas the hypothalamic OT mRNA expression level did not differ between them. Acute intraperitoneal administration of OT during the dark phase reduced the body weight gain and food intake in PCOS model rats, but these effects were not observed in control rats. In contrast, chronic administration of OT decreased the food intake in both the PCOS model rats and control rats. These findings indicate that OT may be a candidate medicine that is efficacious, safe, and continuable for treating obese PCOS patients.

Effect of intraperitoneal docetaxel on ovarian function in mice.

Taxanes are important chemotherapeutic agents used to manage breast cancer and gynaecological malignancies. However, ovarian toxicity induced by the taxane docetaxel (DOC) is of great concern. We investigated DOC-induced toxicity in the ovaries of female CD1 strain mice. The mice were divided into control (saline), DOC-5 (5 mg/kg DOC), and DOC-10 (10 mg/kg DOC) groups and administered saline or DOC on the first day of the study and two weeks later. Two weeks after the second dose, the ovaries were removed for analysis after inducing superovulation. Ovary weight, the number of secondary follicles, and the total number of follicles were reduced after DOC administration. Additionally, the expression levels of caspase-3 and the pro-apoptotic protein Bcl-2 interacting mediator of cell death (BIM) increased. Our findings suggest that high-dose DOC induces damage to growing follicles; however, it may not affect primordial follicles.Impact statementWhat is already known on this subject? Docetaxel (DOC) is one of the most effective chemotherapeutic agents used to manage various cancers. Some in-vitro studies have examined paclitaxel-induced ovarian toxicity; however, limited research on DOC is available.What do the results of this study add? We investigated DOC-induced ovarian toxicity in female CD1 strain mice at 5 mg/kg and 10 mg/kg. We found that DOC reduced ovary weight, the number of secondary follicles, and the total number of follicles, with the higher dose having a higher effect.What are the implications of these findings for clinical practice and/or further research? We believe that our study makes a significant contribution to the knowledge about the effect of DOC on ovarian function.

Effects of low energy availability on female reproductive function.

BACKGROUND: It is known that metabolic and nutritional disturbances induce reproductive dysfunction in females. The main cause of these alterations is reduced gonadotrophin-releasing hormone (GnRH) secretion from the hypothalamus, and the underlying mechanisms have gradually been elucidated. METHODS: The present review summarizes current knowledge about the effects of nutrition/metabolism on reproductive functions, especially focusing on the GnRH regulation system. MAIN FINDINGS: Various central and peripheral factors are involved in the regulation of GnRH secretion, and alterations in their activity combine to affect GnRH neurons. Satiety-related factors, i.e., leptin, insulin, and alpha-melanocyte-stimulating hormone, directly and indirectly stimulate GnRH secretion, whereas orexigenic factors, i.e., neuropeptide Y, Agouti-related protein, orexin, and ghrelin, attenuate GnRH secretion. In addition, kisspeptin, which is a potent positive regulator of GnRH, expression is reduced by metabolic and nutritional disturbances. CONCLUSION: These neuroendocrine systems may be defensive mechanisms, which help organisms to survive adverse conditions by temporarily suppressing reproduction.

A novel PCOS rat model and an evaluation of its reproductive, metabolic, and behavioral phenotypes.

BACKGROUND: Although animal models of PCOS have been used in many studies, none of them can reproduce both the reproductive and metabolic phenotypes of PCOS. In addition, behavioral parameters have not been evaluated in PCOS animal models. PURPOSE: We tried to produce an improved rat model of PCOS, and the reproductive, metabolic, and behavioral phenotypes of the model rats were evaluated. METHODS: Female rats were implanted with silicon tubes containing oil-dissolved dihydrotestosterone (Oil-DHT) as a new PCOS model. Their phenotypes were compared with those of conventional PCOS model rats (DHT), into which tubes containing crystalline DHT were implanted, and non-DHT-treated rats (control). RESULTS: Both the Oil-DHT and DHT rats showed greater body weight gain, food intake, and fat depot weight than the control rats. Furthermore, these groups showed fewer estrous stages and increased numbers of cystic follicles. The DHT rats exhibited lower ovarian and uterine weights than the control rats, whereas no such changes were observed in the Oil-DHT rats. The Oil-DHT and DHT rats showed less locomotor activity in the light phase than the control rats. CONCLUSIONS: Our proposed PCOS model reproduced both the reproductive and metabolic phenotypes of PCOS and may have potential for PCOS research.

Monochorionic Dizygotic Twins Conceived Spontaneously Showed Chimerism in Karyotype and Blood Group Type.

We report a very rare case of monochorionic dizygotic twins conceived spontaneously. The fetuses were sex-discordant in ultrasonography despite being monochorionic twins. After birth, the girl and boy showed normal phenotypes but they showed blood chimerism in karyotype and blood group type.

Sonographic detection and localization of fistulas in fetuses with imperforate anus: Case reports.

Imperforate anus (IA) requires urgent treatment after birth, which is dependent on the type of IA, and is also frequently associated with other congenital abnormalities. Most patients with IA have an accompanying fistula, whose location is strongly associated with the type of IA. The fistula location can be a key factor in defining appropriate treatment, especially in neonates presenting with severe associated abnormalities. Herein, we report three cases of IA in which fistulas were detected and localized prenatally. Examination of the fetal pelvis through the sagittal or coronal view, using high-frequency transducers, revealed the location of the fistulas. In particular, the sagittal view obtained using the fetal infracoccygeal or perineal approach allowed us to determine the precise anatomy of the fistulas. Neonatal assessment confirmed the fistula locations. We recommend using the sagittal view obtained using the fetal infracoccygeal or perineal approach with high-frequency transducers to assess fistulas in fetuses with IA.

Usefulness of measurement of proximal phalanx length by using ultrasonography in newborn infants.

The purpose of this study was to compare digit lengths and proximal phalanx lengths in newborn infants by using ultrasonography (USG) and to examine sex differences between the ratio of the second digit (2D) and fourth digit (4D) of digit length and that of proximal phalanx length and the associations of digit length and proximal phalanx length with birth weight and birth height. Sixty newborn infants (28 males and 32 females) were recruited. Digit lengths were measured by using a transparent ruler and proximal phalanx lengths were measured by using USG. There were significant correlations between digit length and proximal phalanx length in the left and right hands. There was no significant correlation between 2D:4D ratios of digit lengths and 2D:4D ratios of proximal phalanx lengths measured by using USG. In males, birth height was significantly associated with right fourth proximal phalanx length and with left second and fourth proximal phalanx lengths. Birth weight was significantly associated with proximal phalanx length in males. Proximal phalanx length measured by using USG was significantly associated with digit length in newborn infants. Hormonal exposure before birth may be involved in the associations of proximal phalanx length with birth weight and height in males.Impact statementWhat is already known on this subject? The ratio of the second digit (2D) and fourth digit (4D) has been used postnatally to provide a retrospective indication of the foetal hormonal environment. Digit lengths have been measured by using a direct method, photocopies, digital scans and radiographs, but the results of a study on measurement of digit lengths by using ultrasonography (USG) have not been reported.What do the results of this study add? Proximal phalanx length measured by using USG was significantly associated with digit length in newborn infants. In males, birth height was significantly associated with right fourth proximal phalanx length and with left second and fourth proximal phalanx lengths. Birth weight was significantly associated with proximal phalanx length in males.What are the implications of these findings for clinical practice and/or further research? Measurement of proximal phalanx length by using USG may be useful for a study on gender differences in foetal development and the foetal hormonal environment. Hormonal exposure before birth may be involved in the associations of proximal phalanx length with birth weight and height in males.

New treatment strategies for uterine sarcoma using secreted frizzled­related proteins.

Secreted frizzled-related proteins (SFRPs) are involved in the development of various types of cancer and function by suppressing the Wnt signaling pathway. To elucidate the clinical implications of SFRPs in uterine sarcoma, SFRP expression levels and their effects on uterine leiomyosarcoma cells were examined. Immunostaining for SFRP4 was performed on uterine smooth muscle, uterine fibroid and uterine leiomyosarcoma tissues. Additionally, the effects of SFRP4 administration on cell viability, migration and adhesion were evaluated in uterine leiomyosarcoma SKN cells using the WST-1 assay (Roche Diagnostics) and the CytoSelect™ 24-well Cell Migration Assay Kit and the CytoSelect™ 48-well Cell Adhesion Assay Kit. The expression levels of SFRP4 in uterine leiomyosarcoma tissues were lower than those in normal smooth muscle and uterine fibroid tissues. In addition, SFRP4 suppressed the viability and migration, and increased the adhesion ability of uterine leiomyosarcoma cells compared with in the control group. In conclusion, SFRP4 may suppress the viability and migration, and enhance the adhesion of sarcoma cells. These results suggested that SFRP4 could be considered as a novel therapeutic target for uterine sarcoma.

Stress responses to bacterial and viral mimetics in polycystic ovary syndrome model rats.

Polycystic ovary syndrome (PCOS) is associated with an increased risk of psychological distress as well as enhanced responses to psychosocial stress. Recently, it was hypothesized that PCOS patients may be at high risk of novel COVID-19 infections and worse clinical presentations during such infections. Here, we evaluated the effects of PCOS on stress responses to bacterial and viral mimetics using dihydrotestosterone-induced PCOS model rats. Lipopolysaccharide (LPS; a bacterial mimetic) or polyinosinic-polycytidylic acid (Poly-IC; a viral mimetic) was injected into PCOS model rats (PCOS) and non-PCOS rats (control), and the rats' stress responses were evaluated. In the PCOS group, the rats' anorectic and febrile responses to LPS injection were enhanced, whereas their anorectic and febrile responses to Poly-IC injection were unaltered. The PCOS group also exhibited greater changes in peripheral cytokine levels in response to LPS, but not Poly-IC. On the contrary, after the injection of Poly-IC depressed locomotor activity was more evident in the PCOS group, whereas no such changes were observed after LPS injection. These findings indicate that although the stress responses of PCOS model rats to infection may be enhanced, the patterns of change in stress responses and their underlying mechanisms may differ between bacterial and viral infections.

Developmental Changes in Hypothalamic and Serum Oxytocin Levels in Prenatally Normally Nourished and Undernourished Rats.

Changes in the activities of some metabolic factors have been suggested to increase the risk of conditions associated with the Developmental Origins of Health and Disease (DOHaD). We examined changes in oxytocin (OT), a metabolic factor, and OT receptor (OTR) mRNA levels throughout the developmental period in rats of intrauterine undernutrition. Pregnant rats were divided into two groups: a maternal normal nutrition (mNN) and maternal undernutrition (mUN) group. Serum OT concentrations and hypothalamic mRNA levels of OT and OTR were measured in both offspring at various postnatal stages. Both offspring showed significant increases in serum OT concentrations during the neonatal period, significant reductions around the pubertal period, and significant increases in adulthood. Hypothalamic OT mRNA expression levels gradually increased from the neonatal to pubertal period and decreased in adulthood in both offspring. In the pre-weaning period, hypothalamic OT mRNA expression levels were significantly lower in the mUN offspring than in the mNN offspring. In the mUN offspring, hypothalamic OTR mRNA expression levels transiently increased during the neonatal period, decreased around the pubertal period, and increased again in adulthood, whereas transient changes were not detected in mNN offspring. These changes could affect nutritional and metabolic regulation systems in later life and play a role in the mechanisms underlying DOHaD.

Ultrasonographic assessment of testicular volume in Japanese newborn infants.

Purpose : It is essential to determine normative data of testicular size and penile length in newborn infants in order to assess the development during the fetal period. In this study, we evaluated testicular volumes using ultrasonography and also measured penile lengths in Japanese newborn infants. We also examined the associations of the development of these organs with factors including placental weight and anthropometric data. Methods : One hundred and fifteen full-term male newborn infants were recruited for this study. Testicular size was measured by ultrasonography. Results : Mean testicular volumes were 187.4 mm3 in the right testis and 185.4 mm3 in the left testis, and there was no significant difference between the right and left testicular volumes. Right and left testicular volumes showed positive and significant correlations with body lengths and weights. Testicular volumes in the right and left sides were not significantly associated with penile lengths. In 4 groups according to gestational weeks, testicular volume increased significantly with advance of gestational weeks in the left testis. Conclusion : We determined testicular volumes using ultrasonography in Japanese newborn infants. We believe that the results for newborn infants provide important information for assessment of the development of fetal testicular volume. J. Med. Invest. 69 : 256-260, August, 2022.

Ultrasonographic changes in quadriceps femoris thickness in women with normal pregnancy and women on bed rest for threatened preterm labor.

This study aimed to evaluate the changes in quadriceps femoris muscle thickness during the pregnancy and postpartum periods and to elucidate the effect of bed rest for threatened preterm labor on muscle thickness. In 26 women with normal pregnancy, quadriceps femoris thickness was measured at 11-13, 26, 30, and 35 weeks' gestation, and at 3-5 days and 1 month postpartum using ultrasonography. In 15 pregnant women treated with bed rest for threatened premature labor, quadriceps femoris thickness was measured at 30 and 35 weeks' gestation and postpartum. In women with normal pregnancy, quadriceps femoris thickness increased, peaking at 35 weeks' gestation, followed by a postpartum decrease. In women on bed rest, quadriceps femoris thickness showed no significant change during the pregnancy and postpartum periods, and the muscle was significantly thinner at 35 weeks' gestation than that in women with normal pregnancy. In conclusion, a significant increase in quadriceps femoris muscle thickness during normal pregnancy was found using ultrasonography. Meanwhile, in pregnant women on bed rest treatment, the quadriceps femoris was significantly thinner in the late third trimester than that in normal pregnant women. Prolonged bed rest can affect normal changes in the quadriceps femoris muscle thickness during the pregnancy and postpartum periods.

Changes in Serum Oxytocin Levels under Physiological and Supraphysiological Gonadal Steroid Hormone Conditions in Women of Reproductive Age: A Preliminary Study.

Oxytocin (OT) affects many behavioral, psychological, and physiological functions, including appetite and body weight regulation. Central and peripheral OT levels are markedly affected by gonadal steroids, especially estrogen, and the anorectic effects of estrogen are partially mediated by OT in rodents. In this study, the relationship between the estrogen milieu and serum OT levels was evaluated in women of reproductive age under physiological (n = 9) and supraphysiological estrogenic conditions (n = 7). Consequently, it was found that serum OT levels were increased in physiological (the ovulatory phase) and supraphysiological (on the day of the human chorionic gonadotropin trigger in an ovarian stimulation cycle) estrogenic conditions, and that serum OT levels were positively correlated with serum estradiol levels. On the other hand, serum OT levels were negatively correlated with serum progesterone levels, and there was no correlation between serum and follicular OT levels. These results suggest that OT levels may be positively and negatively regulated by estrogen and progesterone, respectively, in humans. However, the physiological roles of these actions of gonadal steroids on OT remain unclear.

Pilot study of a combination of S-1 and paclitaxel for patients with peritoneal metastasis from gastric cancer.

BACKGROUND: This pilot study was carried out to evaluate the efficacy of chemotherapy for patients with peritoneal dissemination from gastric cancer or positive lavage cytology diagnosed by staging laparoscopy. METHODS: Sixteen patients were enrolled. Paclitaxel was administered at 120 mg/m(2) on day 1 and S-1 was administered orally at 80 mg/m(2) for 14 consecutive days, followed by a 1-week rest, as one course. After five courses of this therapy, the primary gastric tumors were evaluated and second-look laparoscopy was performed for patients showing partial response or stable disease with clinical benefit. RESULTS: Partial response or stable disease with clinical benefit was confirmed in seven and five patients, respectively, and these patients underwent second-look laparoscopy. No viable cancer cells were detected on cytopathological investigation during second-look laparoscopy in 9 patients who underwent surgical treatment. The intent-to-treat response rate for gastric tumor was 44% and the rate of disappearance of peritoneal metastasis was 38% (6 cases) at surgery. The median survival time was 555 days. Leucopenia of grade 3 and neutropenia of grade 3 were recognized in two and three patients, respectively. CONCLUSION: This chemotherapy regimen may be an acceptable option for patients with peritoneal dissemination. We plan to study this regimen further in gastric cancer patients with peritoneal dissemination.

[Case report--a long-term surviving patient who received lymph node dissection of skip metastasis from rectosigmoid cancer to bilateral lateral lymph nodes].

Skip metastasis in colorectal cancer consists of about 10% of lymph node metastases. We report a rare long-term surviving patient of skip metastasis to lateral nodes after lymph node dissection. A forty-two years old female received anterior resection for advanced rectosigmoid cancer. Because pathological stage of the patient was stage IIIa (T3N1M0), standard adjuvant chemotherapy was provided. Serum CEA increased just two years after the first operation. PET scan showed abnormal FDG uptake in lymph nodes along the aorta. Lymph nodes along the inferior mesenteric artery (IMA), bilateral common iliac artery and aorta were dissected. There were metastases to nodes along the common iliac artery but no metastasis along the IMA was observed. So we diagnosed it as skip metastasis. The patient is still alive without any metastasis after 6 years from the second operation.