Pleomorphic Rhabdomyosarcoma of the Uterine Corpus in an Adult Who Underwent Multi-gene Panel Testing.

Background/Aim: Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children. Adult primary RMS of gynecological origin is a rare condition and uterine RMS is an aggressive malignancy with a poor prognosis. The genetic variants associated with uterine RMS in adults have yet to be fully elucidated, and there is no established therapeutic strategy for rare tumors. Case Report: A 69-year-old Japanese woman was referred to our hospital with abdominal bloating. Imaging examination revealed a tumor with diameter of 85 mm located in the uterus and multiple regional lymph node metastases. Biopsy of the uterine corpus indicated possible uterine carcinosarcoma or RMS. Following debulking surgery, the patient was diagnosed with stage IVB pleomorphic RMS. The patient was treated with two courses of doxorubicin every three weeks and one course of combination chemotherapy with vincristine, actinomycin, and cyclophosphamide. Because of rapid progression of the disease, we decided to perform multi-gene panel testing to determine the most effective therapeutic strategy. However, no therapeutic plan based on genetic information was identified. The patient with chemotherapy-refractory RMS died 11 weeks after surgery. Conclusion: Our patient had advanced uterine RMS with an unresectable tumor that was resistant to chemotherapy, resulting in poor outcomes. Despite conducting multi-gene panel testing, no tailored therapeutic approach based on genetic information was found. This case highlights the challenges in managing uterine RMS in adults and underscores the urgent need for further research to identify effective treatment modalities.

Reinfusion of peritoneal fluid elevates the level of plasma D-dimer in patients with early-onset ovarian hyperstimulation syndrome.

Purpose: This study aimed to elucidate the factors that affect the dynamics of blood D-dimer in ovarian hyperstimulation syndrome (OHSS). Methods: We retrospectively reviewed medical records from two hospitals and extracted data obtained during assisted reproductive technology and OHSS treatment. Blood D-dimer levels during hospitalization were plotted against body weight. Other factors possibly related to blood D-dimer levels were also analyzed. Results: The analysis included 10 patients with OHSS admitted between January 2013 and June 2023. In all patients, blood D-dimer levels increased significantly when they convalesced from OHSS and lost weight. None of the patients showed clinical signs of thrombosis, which was confirmed using imaging tests in 8 of 10 patients. Two patients underwent cell-free and concentrated ascites reinfusion therapy (CART), and their blood D-dimer levels increased dramatically after the procedure. Conclusion: Weight change and CART are associated with blood D-dimer dynamics in OHSS. Our results show that elevated blood D-dimer levels in patients with OHSS do not always represent the presence of thrombosis. Reinfusion of pooled D-dimer in ascites may explain the D-dimer surge during the recovery phase or after CART in these patients. Our study provides new perspectives on the clinical implications of D-dimer during OHSS.

Lipid droplets synthesized during luteinization are degraded after pregnancy.

After pregnancy, the corpus luteum (CL) functions as a transient endocrine gland that produces progesterone, which is necessary to maintain pregnancy. To maintain constant progesterone production, CLs are enriched in lipids as its precursors. Lipid droplets (LDs) are organelles that originate from the endoplasmic reticulum and store neutral lipids such as triacylglycerols and cholesteryl esters. The size and number of LDs in a cell are regulated by LD-associated proteins that coat their surface. LD degradation is regulated by either neutral lipid hydrolases (lipolysis), selective autophagic mechanism (lipophagy), or both. Mammalian CLs are long known to be enriched in LDs, but LDs are rapidly depleted after pregnancy and reappear near the time of delivery. In this present study, we hypothesized that LDs synthesized by luteinization are massively degraded after pregnancy. Using mCherry-HPos mice, in which LD synthesis can be visualized in vivo, we found that LD synthesis, which was activated during luteal development, was suppressed after implantation. In CLs, LD synthesis remained low during pregnancy, but was reactivated before and after delivery. These changes in LDs were confirmed using electron microscopy and immunostaining. Furthermore, LD degradation was mediated by lipolysis rather than lipophagy. In summary, our findings indicate that luteinization-induced LD synthesis is suppressed after pregnancy onset and that CLs are lipid-poor during pregnancy because LDs stored during luteal development are extensively degraded by lipolysis.

Physicians' Perspective Toward Hypertensive Disorders of Pregnancy and Future Cardiovascular Diseases in Japan.

AIM: Hypertensive disorders of pregnancy (HDP) are among the obstetric complications reportedly associated with later-life cardiovascular disease (CVD). This study examined physicians' recognition of reproductive history by elucidating their attitude and knowledge. METHODS: This study included council members of the Japan Atherosclerosis Society. An Internet-based survey was conducted between August 9 and September 9, 2022. RESULTS: A total of 137 council members completed the questionnaire (response rate: 36%). In terms of the internal medicine subspeciality of the participants, endocrinology was the most common (46%), followed by cardiology (38%). About 70% of the participants considered reproductive history to be important and obtained more information than those who considered it otherwise. In the questionnaire for knowledge about HDP and future diseases, physicians correctly answered 6.8 of 9 questions. Endocrinologists were more likely to ask regarding reproductive history at the initial visit than cardiologists (82.5% vs. 61.5%; p=0.012) and obtained more information from women below 50 years old. Contrarily, cardiologists obtained information on reproductive history from older women (those approaching menopause and those in their 60s and 70s). CONCLUSION: We found that physicians had a high level of knowledge about HDP and the importance of reproductive information. However, the manner of obtaining information, including the target population, differed depending on the subspeciality. In the future, effective interventions for women with a history of HDP need to be developed in order to encourage physicians to obtain reproductive information to prevent CVD.

PCSK9 inhibitor use during pregnancy in a case of familial hypercholesterolemia complicated with coronary artery disease.

Limited data have been reported on the use of proprotein convertase subtilisin/kexin type 9 (PCSK 9) inhibitors during pregnancy in women with familial hypercholesterolemia (FH). Here, we present the first case of initiating evolocumab (PCSK9 inhibitor) in a compound heterozygous FH mother. The patient was a 34-year-old primipara with severe dyslipidemia and a history of coronary artery bypass surgery. An elevated low-density lipoprotein cholesterol (LDL-C) level of 420 mg/dL was detected in the first trimester and persistently increased throughout pregnancy. Evolocumab was administered at 31 and 35 weeks of gestation, showing a positive effect on stabilizing LDL-C levels. Planned delivery with labor analgesia was performed at 38 + 4 weeks. Both the mother and infant were discharged without any notable complications. Hence, evolocumab, an IgG2 monochromatic antibody with little placental permeability, may be an alternative medication with limited influence on infants. Further studies are needed to assess the safety of evolocumab administration during pregnancy.

Ambient temperature and preterm birth: A case-crossover study.

OBJECTIVE: To investigate the association between ambient temperature and preterm birth (PTB) and to estimate the population attributable fraction (PAF) of PTBs due to low and high temperatures. DESIGN: Time-stratified case-crossover design. SETTING: Japan (46 prefectures, excluding Okinawa), 2011-2020. SAMPLE: 214 050 PTBs registered in the Japan Perinatal Registry Network database among 1 908 168 singleton live births. METHODS: A quasi-Poisson regression model with a distributed lag nonlinear model was employed to assess the associations between daily mean temperature and PTBs for a lag of 0-27 days in each prefecture. A random effects meta-analysis was conducted by combining effect estimates from the 46 prefectures to estimate pooled relative risks (RRs). The PAFs of the PTBs due to below or above the mean of the 46 median temperatures (16.0°C) were calculated. MAIN OUTCOME MEASURES: Preterm singleton live births. RESULTS: The association between daily mean temperature and PTB risk exhibited a U-shaped curve. The adjusted RRs were 1.15 (95% confidence interval [CI] 1.05-1.25) at the mean of the 1st percentiles (0.8°C) and 1.08 (95% CI 1.00-1.17) at the mean of the 99th percentiles (30.2°C) of 46 prefectures, with 16.0°C as the reference temperature. Approximately 2.3% (95% CI 0.6-4.0) of PTBs were attributable to low temperatures. CONCLUSIONS: Both low and possibly high temperatures were associated with an increased risk of PTBs. These findings may help to inform preventive measures for pregnant women.

Effective gestational weight gain advice to optimize infant birth weight in Japan based on quantile regression analysis.

The optimal range of gestational weight gain (GWG) was recently raised in Japan. This may help reduce small-for-gestational-age (SGA) infants, but may also increase large-for-gestational-age (LGA) infants. This study performed hypothetical experiments to determine effective GWG advice based on quantile regression analysis. In a total of 354,401 singleton pregnancies registered in the perinatal database of the Japan Society of Obstetrics and Gynecology (2013-2017), the proportions of SGA and LGA were 9.33% and 11.13%, respectively. Using regression coefficients of GWG across the birth weight-for-gestational-age quantile distribution, we analyzed changes in their proportions by simulating a uniform 3-kg extra increase in GWG or an increase or decrease based on GWG adequacy. A hypothetical experiment of a uniform increase in GWG resulted in SGA and LGA proportions of 7.26% (95% confidence interval 7.15-7.36) and 14.51% (14.37-14.66), respectively. By contrast, assuming a 3-kg increase in women with inadequate GWG and a 3-kg decrease in women with excessive GWG resulted in SGA and LGA proportions of 8.42% (8.31-8.54) and 11.50% (11.37-11.62), respectively. Our real-world data analysis suggests that careful adjustment of GWG based on GWG adequacy will be effective in optimizing infant birth weight in Japan.

Maternal body mass index is not associated with assisted reproductive technology outcomes.

The effects of body mass index (BMI) on assisted reproductive technology (ART) outcomes such as ovarian dysfunction, poor ovum quality, and endometrial dysfunction have been studied; however, many aspects remain controversial. Therefore, we retrospectively investigated the relationship between BMI and ART outcomes. For 14,605 oocyte retrieval cycles at our hospital between January 2016 and December 2020, BMI was divided into five groups (< 18.5, 18.5-20.0, 20.0-22.5, 22.5-25.0, ≥ 25 kg/m2) and measured before oocyte retrieval. The normal fertilization and high-grade blastocyst rates were compared. In addition, in the 7,122 frozen-thawed embryo transfers (FET) with highest-grade embryos, the clinical pregnancy, miscarriage, and live birth rates were investigated in the five BMI groups. Multiple regression analysis on normal fertilization and high-grade blastocyst rates revealed no statistically significant differences. Furthermore, after propensity score matching on FET, there was no significant difference in clinical pregnancy, miscarriage, and live birth rates in the BMI groups. BMI is a risk factor for complications during pregnancy; however, it does not affect ART outcomes. Therefore, we believe weight guidance should be provided to women with obesity at the start of infertility treatment, but treatment should not be delayed.

Prenatal vitamin D deficiency alters immune cell proportions of young adult offspring through alteration of long-term stem cell fates.

Vitamin D deficiency is a common deficiency worldwide, particularly among women of reproductive age. During pregnancy, it increases the risk of immune-related diseases in offspring later in life. However, exactly how the body remembers exposure to an adverse environment during development is poorly understood. Herein, we explore the effects of prenatal vitamin D deficiency on immune cell proportions in offspring using vitamin D deficient mice established by dietary manipulation. We show that prenatal vitamin D deficiency alters immune cell proportions in offspring by changing the transcriptional properties of genes downstream of vitamin D receptor signaling in hematopoietic stem and progenitor cells of both the fetus and adults. Further investigations of the associations between maternal vitamin D levels and cord blood immune cell profiles from 75 healthy pregnant women and their term babies also confirm that maternal vitamin D levels significantly affect immune cell proportions in the babies. Thus, lack of prenatal vitamin D, particularly at the time of hematopoietic stem cell migration from the liver to the bone marrow, has long-lasting effects on immune cell proportions. This highlights the importance of providing vitamin D supplementation at specific stages of pregnancy.

Step-by-step instructions for detecting whirlpool sign in adnexal torsion.

Objective: Adnexal torsion is a common gynecological emergency whose prompt diagnosis is essential because a delay may lead to ovarian dysfunction. Although the whirlpool sign is reliable for diagnosing ovarian cyst torsion, technical difficulties hinder its use by sonographers. Here we developed a systematic approach to visualizing this sign by focusing on the fact that torsion arises from the space between the uterus and the pelvic wall. One must determine the origin of the torsion via transverse imaging of the uterus and follow the twisted ligaments to the ovarian cyst. Patients and Methods: Two women aged 56 (Case 1) and 28 years (Case 2) visited our hospital with lower abdominal pain. Transvaginal ultrasonography showed a 7-cm right ovarian cyst in Case 1 and a 5-cm cyst in the Douglas pouch in Case 2; normal bilateral ovaries and the whirlpool sign were detected in both cases. Under laparoscopic guidance in Cases 1 and 2, an ovarian cyst and a paraovarian cyst were confirmed and removed. Results: Our step-by-step method allowed us to identify the whirlpool sign and confirm adnexal torsion, leading to prompt surgery in both cases. Conclusion: Using a systematic procedure helps less experienced practitioners detect the whirlpool sign.

COVID-19 mRNA vaccination status and concerns among pregnant women in Japan: a multicenter questionnaire survey.

BACKGROUND: mRNA vaccination is an effective, safe, and widespread strategy for protecting pregnant women against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, information on factors such as perinatal outcomes, safety, and coverage of mRNA vaccinations among pregnant women is limited in Japan. Therefore, this study aimed to investigate the perinatal outcomes, coverage, adverse effects, and short-term safety of mRNA vaccination as well as vaccine hesitancy among pregnant women. METHODS: We conducted a multicenter online survey of postpartum women who delivered their offspring at 15 institutions around Tokyo from October 2021 to March 2022. Postpartum women were divided into vaccinated and unvaccinated groups. Perinatal outcomes, COVID-19 prevalence, and disease severity were compared between the two groups. Adverse reactions in the vaccinated group and the reasons for being unvaccinated were also investigated retrospectively. RESULTS: A total of 1,051 eligible postpartum women were included. Of these, 834 (79.4%) had received an mRNA vaccine, while 217 (20.6%) had not, mainly due to concerns about the effect of vaccination on the fetus. Vaccination did not increase the incidence of adverse perinatal outcomes, including fetal morphological abnormalities. The vaccinated group demonstrated low COVID-19 morbidity and severity. In the vaccinated group, the preterm birth rate, cesarean section rate, and COVID-19 incidence were 7.2%, 33.2%, and 3.3%, respectively, compared with the 13.7%, 42.2%, and 7.8% in the unvaccinated group, respectively. Almost no serious adverse reactions were associated with vaccination. CONCLUSIONS: mRNA vaccines did not demonstrate any adverse effects pertaining to short-term perinatal outcomes and might have prevented SARS-CoV-2 infection or reduced COVID-19 severity. Concerns regarding the safety of the vaccine in relation to the fetus and the mother were the main reasons that prevented pregnant women from being vaccinated. To resolve concerns, it is necessary to conduct further research to confirm not only the short-term safety but also the long-term safety of mRNA vaccines.

Diet Quality and Its Relationship with Weight Characteristics in Pregnant Japanese Women: A Single-Center Birth Cohort Study.

Maternal underweight and inadequate gestational weight gain (GWG) are problems in Japan. However, increases in food intake aimed at weight gain alone are not sufficient for mother-child health. This study assessed diet quality based on the 3-day dietary records of pregnant women in an urban area of Japan in order to show the importance of evaluating diet quality, using the Nutrient-Rich Food Index 9.3 (NRF9.3), which is one metric based on nutrition profiling, and the Japanese Food Guide Spinning Top (JFGST). After excluding misreporters of energy intake, we stratified women (n = 91) by pre-pregnancy body mass index (BMI) and determined energy intake, diet quality status, and their relationship with GWG. Intakes of carbohydrate-containing staple foods, vegetable dishes, and fruit were insufficient regardless of BMI. Most of the underweight women with inadequate GWG had insufficient energy intake but high diet quality, as assessed by NRF9.3. In contrast, most women who consumed energy within the recommended range had low diet quality and gained weight at inappropriate levels. These results highlight the importance for pregnant Japanese women to maintain diet quality through a nutrient-dense diet, while simultaneously increasing energy intake after evaluation of their individual diet quality.

17α-ethinylestradiol modulates endothelial function in ovariectomized rat carotid arteries.

17α-ethinylestradiol (EE2), a derivative of 17ß-estradiol (E2), is a potent estrogenic substance that is used as the estrogenic component of oral contraceptives (OCPs). However, women who take OCPs have an increased risk of cardiovascular events. Since few studies have examined EE2 endothelial effects, we explored the effects of EE2 on endothelial function in ovariectomized and isoflavone-free rats. After ovariectomy, 12-week-old female Sprague-Dawley rats were assigned to EE2, E2 or control groups. After 16 weeks, the EE2 and E2 groups were orally administered EE2 (8.3 µg/day) and E2 (12.6 µg/day) for 4 weeks, respectively. At 18 weeks, endothelial denudation of the left common carotid arteries was performed, and they were harvested at 20 weeks. The rats in the EE2 and E2 groups exhibited significantly decreased body weights and significantly increased uterine weights, respectively, but no differences were observed between the EE2 and E2 groups. The EE2 and E2 groups showed significantly enhanced acetylcholine-induced endothelium-dependent relaxation, with apamin plus charybdotoxin inhibiting only the EE2 group. Endothelial nitric oxide (NO) synthase expression was significantly higher in the EE2 group than in the control, but lower than in the E2 group. The intima-to-media ratio of denuded arteries was significantly lower in the E2 group than in the other groups, suggesting that NO decreased in the EE2 group compared to the E2 group. We conclude that EE2 has a weaker ability than E2 to produce NO and, for the first time, we demonstrate the ability of EE2 to enhance the activity of endothelial-derived hyperpolarizing factor.

A possible function of Nik-related kinase in the labyrinth layer of delayed delivery mouse placentas.

In mice and humans, Nik-related protein kinase (Nrk) is an X-linked gene that encodes a serine/threonine kinase belonging to GCK group 4. Nrk knockout (Nrk KO) mice exhibit delayed delivery, possibly due to defective communication between the Nrk KO conceptus and its mother. However, the mechanism of delayed labor remains largely unknown. Here, we found that in pregnant mothers with the Nrk KO conceptus, the serum progesterone (P4) and placental lactogen (PL-2) concentrations in late pregnancy were higher than those in the wild type. Moreover, we demonstrated that Nrk is expressed in trophoblast giant cells (TGCs) and syncytiotrophoblast-2 (SynT-2) in the labyrinth layer of the mouse placenta. In the human placenta, NRK is also expressed in Syn-T in villi. Both human Syn-T and mouse TGCs of the labyrinth layer are present within fetal tissues that are in direct contact with the maternal blood. The labyrinth layer of the Nrk KO conceptus was gigantic, with enlarged cytoplasm and Golgi bodies in the TGCs. To investigate the function of Nrk in the labyrinth layer, a differentially expressed gene (DEG) analysis was performed. The DEG analysis revealed that labor-promoting factors, such as prostaglandins, were decreased, and pregnancy-maintaining factors, such as the prolactin family and P4 receptor, were increased. These findings suggest that the Nrk KO mice exhibit delayed delivery owing to high P4 concentrations caused by the hypersecretion of pregnancy-maintaining factors, such as PL-2, from the placenta.

Investigation of exacerbating factors for postpartum hair loss: a questionnaire-based cross-sectional study.

Background: Although postpartum hair loss is believed to be common, there is little reliable information. Objective: We sought to examine the factors that were associated with postpartum hair loss and to elucidate factors correlated with its pathogenesis. Methods: We carried out a questionnaire-based cross-sectional study. The study participants were women who delivered at 2 facilities and filled the questionnaire 10-18 months after delivery. The survey questionnaire included baseline characteristics, pregnancy details, delivery, childcare, and extent of postpartum hair loss. We divided participants into 2 groups according to the absence or presence of postpartum hair loss and performed logistic regression analyses. Results: A total of 331 (21.0%) responses were analyzed; among these 304 (91.8%) women had postpartum hair loss. The average time for the start, peak, and end of hair loss was 2.9, 5.1, and 8.1 months, respectively. Women with hair loss had an earlier time of delivery, a lower birth weight, a higher preterm labor rate, and longer-term breastfeeding. Logistical regression analyses revealed that longer-term breastfeeding and preterm labor were independent predictors of postpartum hair loss. The adjusted odds ratio for postpartum hair loss in women who ended breastfeeding 6-12 months postpartum versus those who ended it after 12 months or more was 5.96 (95% confidence interval [CI] [1.68, 21.09]) and 6.37 (95% CI [1.95, 20.76]) compared with those who stopped breastfeeding within 6 months postpartum. Limitations: Finer details such as pregnancy complications and delivery information may not be accurate since all results are based on questionnaire responses. There may be a sampling bias because women who suffer from postpartum hair loss may tend to participate more frequently. Conclusion: Over 90% of women experienced postpartum hair loss. Our data show that long-term breastfeeding and preterm labor correlate with postpartum hair loss.

Impact of paternal age on IVF and pregnancy outcomes with only normal sperm parameters.

OBJECTIVE: Previous reports on advanced paternal age effects on assisted reproductive technology (ART) vary considerably and those on frozen-thawed embryo transfer (FET) are rare. We investigated whether paternal age affects in vitro fertilisation (IVF) and FET pregnancy outcomes. MATERIALS AND METHODS: 1657 IVF cycles performed from January 2014 to May 2018 were retrospectively investigated excluding cases of poor semen parameters. Paternal and maternal ages were categorised into groups, namely, <35, 35-39 and ≥ 40 years, to compare normal fertilisation (2 PN (pronuclei)) and high-quality blastocyst rates. Furthermore, 741 FET cycles were investigated and pregnancy, live birth and miscarriage rates were compared. RESULTS: For the maternal age group (35-39), the 2 PN rate was significantly higher with paternal age group of <35 than groups of 35-39 and ≥ 40 (median%, <35 vs. 35-39 vs. ≥40 = 100.0 vs. 71.4 vs. 77.7; P = 0.005). The miscarriage rate was significantly higher with paternal age group of ≥40 than that of <35 and 35-39 when maternal age was <35 (median %, <35 vs. 35-39 vs. ≥40 = 13.1 vs. 7.8 vs. 33.3; P = 0.038). CONCLUSION: Our findings show that when maternal age was <35, advanced paternal age reduces the normal fertilisation rate and increases the FET miscarriage rate when maternal age was 35-39.

Pertussis, diphtheria, and tetanus antibodies seroprevalence in pregnant women and neonates, as a preliminary data for introduction of preconception or prenatal DTaP vaccination among Japanese society.

An increasing number of countries have been introducing acellular pertussis vaccination during pregnancy for the prevention of neonatal pertussis. In response to the fact that infantile pertussis cases of 0-5 months age groups remained unchanged despite the universal vaccination program, prenatal pertussis vaccination has been a rising issue in Japan. Hence, we investigated the seroprevalence of pertussis, diphtheria, and tetanus antibodies in Japanese pregnant women and neonates, and evaluated the necessity of diphtheria-tetanus-acellular pertussis (DTaP) vaccination during the preconception or prenatal period. Maternal PT-IgG (EIA) and FHA-IgG (EIA) for the first trimester, within 1 week after delivery, and cord blood were collected, along with colostrum pertussis-IgA (ELISA), diphtheria-IgG (EIA), tetanus-IgG (EIA), and blood samples from the first trimester. The maternal seroprevalence of PT-IgG and FHA-IgG was 69 % and 75 %, respectively. All tested participants were positive for diphtheria-IgG and tetanus-IgG (100 %). First trimester PT-IgG/FHA-IgG antibody titers were significantly associated with cord blood PT-IgG/FHA-IgG titers (P < 0.001). We found that pertussis seroprevalence among pregnant Japanese women was approximately 70 %. The antibody seropositivity rate of pertussis was lower than that of diphtheria and tetanus. Fetal acquired passive immunity against pertussis is higher when the level of maternal antibody in the first trimester is sufficient. At least 30 % of study population did not reach to the threshold value to provide sufficient pertussis immunity for the neonates and themselves. The acellular pertussis vaccine (DTaP) approved in Japan lacks safety information for pregnancy, hence, a solution for prompt administration of prenatal acellular pertussis vaccination might be introducing DTaP in the preconception period.

Body weight and body fat are negatively associated with severe dyspareunia in postmenopausal women.

AIM: This cross-sectional study aimed to investigate the factors associated with dyspareunia in pre-, peri-, and postmenopausal Japanese women participating in the health and nutrition education program at a menopause clinic. METHODS: First-visit records of 1702 pre-, peri-, and postmenopausal Japanese women (aged 40-79 years) were analyzed. The relationship between severe dyspareunia and background characteristics was examined by multivariate logistic regression analysis. RESULTS: The average age of the participants was 53.0 ± 6.3 years. The percentage of women who suffered from severe dyspareunia in the pre-, peri-, postmenopausal, and the hormone therapy receiving groups were 7.1%, 10.5%, 14.6%, and 7.8%, respectively. In the postmenopausal group, the percentage of women affected by severe dyspareunia was the highest between 2 and 5 years after menopause (18.8%), presumably owing to the gradual postmenopausal decline in the number of sexually active women. In sexually active postmenopausal women, body weight, body mass index (BMI), and body fat percentage (BF%) differed significantly among those who had severe dyspareunia (N = 119) and those who did not (N = 334). BMI and BF% were negatively associated with severe dyspareunia, even after adjustment for age and years since menopause (adjusted odds ratio [95% confidence interval]: BMI, 0.894 [0.825-0.964], p = 0.003; BF%, 0.947 [0.909-0.985], p = 0.006). CONCLUSIONS: BMI and BF% were negatively associated with dyspareunia in sexually active postmenopausal women. In addition to aging, the loss of body weight and fat could negatively impact intercourse in sexually active postmenopausal women.

A Review of Delayed Delivery Models and the Analysis Method in Mice.

In humans, the incidence of post-term delivery is 1-10%. Post-term delivery significantly increases the risk of cesarean section or neonatal intensive care unit (NICU) admission. Despite these serious challenges, the cause of prolonged delivery remains unclear. Several common factors of delayed parturition between mice and humans will help elucidate the mechanisms of pregnancy and labor. At present, gene modification techniques are rapidly developing; however, there are limited reviews available describing the mouse phenotype analysis as a human model for post-term delivery. We classified the delayed-labor mice into nine types according to their causes. In mice, progesterone (P4) maintains pregnancy, and the most common cause of delayed labor is luteolysis failure. Other contributing factors include humoral molecules in the fetus/placenta, uterine contractile dysfunction, poor cervical ripening, and delayed implantation. The etiology of delayed parturition is overexpression of the pregnancy maintenance mechanism or suppression of the labor induction mechanism. Here, we describe how to investigated their causes using mouse genetic analysis. In addition, we generated a list to identify the causes. Our review will help understand the findings obtained using the mouse model, providing a foundation for conducting more systematic research on delayed delivery.

GPR110, a receptor for synaptamide, expressed in osteoclasts negatively regulates osteoclastogenesis.

Bone remodeling is precisely regulated mainly by osteoblasts and osteoclasts. Although some G-protein coupled receptors (GPCRs) were reported to play roles in osteoblast function, little is known about the roles in osteoclasts. In this study, we found, for the first time, that the expression of GPR110 increased during osteoclastogenesis. GPR110 belongs to adhesion GPCR and was the functional receptor of N-docosahexaenoyl ethanolamine (also called synaptamide). Synaptamide suppressed osteoclastogenesis induced by receptor activator of nuclear factor-kappa B ligand. Considering that synaptamide is the endogenous metabolite of DHA, we hypothesized that DHA may inhibit osteoclastogenesis by affecting synaptamide/GPR110 signaling. But GPR110 knockout and subsequent rescue experiments revealed a pivotal role of GPR110 in the attenuation of osteoclastogenesis by synaptamide but not by DHA. These results suggest that synaptamide/GPR110 signaling negatively regulates osteoclastogenesis. Our study suggested that ligands of GPR110, such as synaptamide, might be a useful drug for osteoporotic patients.