Smooth muscle electromyography for detecting major alterations in the estrus cycle in rats.

Determining the female animal cycle is crucial in preclinical studies and animal husbandry. Changes in hormone levels during the cycle affect physiological responses, including altered contractility of the visceral smooth muscle. The study aimed to identify estrus and anestrus using smooth muscle electromyographic (SMEMG) measurements, in vivo fluorescent imaging (IVIS) and in vitro organ contractility of the uterus and cecum. The study involved sexually mature female Sprague-Dawley rats, aged 10-12 weeks. The rats received a daily injection of cetrorelix acetate solution for 7 days, while another group served as the control. The animals were subjected to gastrointestinal and myometrial SMEMG. The change in αvß3 integrin activity was measured with IVIS in the abdominal cavity. Contractility studies were performed in isolated organ baths using dissected uterus and cecum samples. Plasma samples were collected for hormone level measurements. A 3-fold increase in spontaneous contraction activity was detected in SMEMG measurements, while a significant decrease in αvß3 integrin was measured in the IVIS imaging procedure. Cetrorelix reduced the level of LH and the progesterone / estradiol ratio, increased the spontaneous activity of the cecum rings, and enhanced KCl-evoked contractions in the uterus. We found a significant change in the rate of SMEMG signals, indicating simultaneous increases in the contraction of the cecum and the non-pregnant uterus, as evidenced by isolated organ bath results. Fluorescence imaging showed high levels of uterine αvß3 integrin during the proestrus-estrus phase, but inhibiting the sexual cycle reduced fluorescence activity. Based on the results, the SMEMG and IVIS imaging methods are suitable for detecting estrus phase alterations in rats.

Enhancing uterine receptivity for embryo implantation through controlled collagenase intervention.

Ineffective endometrial matrix remodeling, a key factor in infertility, impedes embryo implantation in the uterine wall. Our study reveals the cellular and molecular impact of human collagenase-1 administration in mouse uteri, demonstrating enhanced embryo implantation rates. Collagenase-1 promotes remodeling of the endometrial ECM, degrading collagen fibers and proteoglycans. This process releases matrix-bound bioactive factors (e.g., VEGF, decorin), facilitating vascular permeability and angiogenesis. Collagenase-1 elevates embryo implantation regulators, including NK cell infiltration and the key cytokine LIF. Remarkably, uterine tissue maintains structural integrity despite reduced endometrial collagen fiber tension. In-utero collagenase-1 application rescues implantation in heat stress and embryo transfer models, known for low implantation rates. Importantly, ex vivo exposure of human uterine tissue to collagenase-1 induces collagen de-tensioning and VEGF release, mirroring remodeling observed in mice. Our research highlights the potential of collagenases to induce and orchestrate cellular and molecular processes enhancing uterine receptivity for effective embryo implantation. This innovative approach underscores ECM remodeling mechanisms critical for embryo implantation.

Patient with Herlyn-Werner-Wunderlich syndrome and endometriosis achieves successful full-term pregnancy (40 weeks and 6 days): a case report.

INTRODUCTION: Herlyn-Werner-Wunderlich syndrome , a rare Müllerian ducts congenital disease, is characterized by a diphtheritic uterus, blind hemivagina, and ipsilateral renal agenesis. Diagnosis is at young age by ultrasound and magnetic resonance imaging, and the prognosis is good. Usually, complications evolve endometriosis and secondary pelvic inflammation. CASE REPORT: A 40-year-old female patient, Brazilian, white, primigravida, diagnosed at 30 years with a didelphic uterus on ultrasound, and 4 years later, with a left ovarian endometrioma, multiple ovarian cysts, and left renal agenesis on magnetic resonance imaging. Subsequently, due to dyspareunia and a feeling of swelling, the patient underwent transvaginal ultrasound with bowel preparation, and a hematocolpos was found and Herlyn-Werner-Wunderlich syndrome was suspected; 10 years after the diagnosis she had a planned pregnancy. She presented frequent contractions following the 15th week of pregnancy and fortunately there were no complications or premature labor. Labor was inducted at 40 weeks and 6 days without progress and a cesarean section was indicated and performed without complications. Herlyn-Werner-Wunderlich syndrome often goes unnoticed, leading to inadequate treatment. Individuals with Herlyn-Werner-Wunderlich syndrome commonly face fertility issues, such as high miscarriage rate (21-33%), and obstetric complications, such as spontaneous abortions (40% risk), intrauterine growth restriction, postpartum hemorrhage, increased fetal mortality, preterm delivery (21-29%), and elevated rates of cesarean sections. In addition, there is higher susceptibility of developing endometriosis, especially with hemivaginal obstruction, and pelvic adhesions. CONCLUSION: Early diagnosis enables timely treatment and, consequently, fewer complications. Still, when these factors are absent, vaginal birth may still be possible. The true prevalence and incidence of complications related to Herlyn-Werner-Wunderlich syndrome are still unknown.

Efficacy and safety of management of placenta accreta spectrum by transverse uterine fundal incision in a single tertiary care centre: A retrospective study.

Background We assessed the efficacy and safety of management of morbidly adherent placenta by the transfundal uterine incision approach. As a secondary outcome measure, we compared ultrasound and magnetic resonance imaging (MRI) for the diagnosis of adherent placenta. Methods We retrospectively analysed the records of 5 years of women with adherent placenta. Twenty-five women with an antenatal diagnosis of placenta increta and percreta operated by transfundal uterine incision were included. Blood loss, transfusion requirements, operative injuries, and maternal and neonatal intensive care unit (ICU) stay were compared among three different types of adherent placenta. Surgical and other outcome measures were also analysed. Results On antenatal screening with ultrasound, an accurate diagnosis could be achieved in all cases of increta and two-thirds of percreta. Antenatal diagnosis by MRI detected 93.3% of increta and all percreta cases. The mean (SD) gestation at delivery was 34 (4.9) weeks in accreta, 34.9 (2.7) weeks in increta and 31 (4.8) weeks in percreta patients. The mean blood loss encountered intraoperatively was 1012.5 (193.1) ml, 1566.67 (566.52) ml and 1591.67 (629.61) ml in accreta, increta and percreta patients, respectively. Inadvertent bladder injury occurred in 3 women who had placenta percreta invading the bladder. There was no long-term morbidity and no mortality. Conclusion Transfundal incision for delivery of baby is associated with the advantage of avoiding the placenta thereby minimizing blood loss.

Association of congenital uterine anomaly with abnormal placental cord insertion and adverse pregnancy complications: a retrospective cohort study.

OBJECTIVE: Congenital uterine anomalies during pregnancy increase the risk of pregnancy complications such as miscarriage, preterm delivery, fetal malpresentation, cesarean delivery, and fetal growth restriction. However, few studies have examined uterine anomalies in relation to perinatal complications other than those mentioned above. We investigated the association between pregnancies complicated by congenital uterine anomalies and various perinatal outcomes at our institution. METHODS: This retrospective cohort study was conducted from January 2009 to May 2021. We included cases of uterine anomalies, such as septate, bicornuate, unicornuate, and didelphic uterus. First, the perinatal complications and neonatal outcomes were compared between pregnancies complicated by uterine anomalies and those with normal uteri. Second, we conducted an analysis based on the type of uterine anomalies classified into two groups: the minor anomaly group consisted of anomalies limited to the uterine cavity, such as the septate uterus, whereas the major anomaly group included anomalies affecting the uterine shape, such as bicornuate, unicornuate, and didelphic uterus. We compared the incidence of perinatal complications among the major anomaly, minor anomaly, and normal uterus groups. RESULTS: During the study period, 45 pregnancies were complicated with uterine anomalies. The minor anomaly group included 11 patients and the major anomaly group included 34 patients. The incidence of fetal malpresentation was significantly higher in the uterine anomaly group than in the normal uterus group (18% vs. 3.7%, p = .04). Furthermore, the frequency of abnormal placental cord insertion was significantly higher in the uterine anomaly group (16% vs. 3.7%, p = .01). Examination based on the type of uterine anomaly revealed significant differences in cervical incompetence, malpresentation, cesarean section, and abnormal placental cord insertion. Cervical incompetence was more likely in patients with minor anomalies. In contrast, fetal malpresentation, cesarean section, and abnormal placental cord insertion were more likely in the major anomaly group. CONCLUSIONS: In addition to the findings reported in previous studies, abnormal placental cord insertion was more frequent in pregnancies complicated by uterine anomalies.

A new treatment for Robert's uterus with adenomyosis: a case report and review of the literature.

PURPOSE: To provide a method for the differential diagnosis of Robert's uterus with adenomyosis, a rare uterine malformation, and determine the best course of treatment. METHODS: A patient who had Robert's uterus with adenomyosis was admitted to our hospital in December 2022. We analyzed and summarized her case . RESULTS: Our patient complained of progressively worsening primary dysmenorrhea over the course of 3 years and lower abdominal pain lasting for 2 days. Her carbohydrate antigen 125 (CA125) level was 372.10 U/mL. Examinations conducted by several hospitals indicated that she had a single-horned uterus and a residual horned uterus, and our hospital's examination identified Robert's uterus. This malformation was corrected by open abdominal surgery. For the procedure, pelvic adhesions were first isolated, after which the closed uterine cavity and adenomyosis were resected. Subsequently, the left ovarian endometriosis cyst was resected and right tubal ligation was performed. After surgery, three injections of gonadotropin-releasing hormone A (GnRH-A) were administered, which lowered the patient's CA125 level to 14 U/mL and normalized her condition. CONCLUSION: We pioneered a new therapeutic approach for the treatment of Robert's uterus with adenomyosis. Some valuable references are provided for clinical practice.

Study on the value of MRI in locating the internal OS of the cervix and influencing factors.

The position of the internal os of the cervix reported in the literature was inconsistent on MRI images. Additionally, the practical impactful data influencing the internal os located by MRI is limited. We aimed to confirm the position of the internal os of the cervix on MRI images, and the influencing factors locating the the internal os by MRI. A single-center retrospective study was conducted. Data from 175 patients who underwent total hysterectomy for stage I endometrial cancer were collected. The internal os of the cervix is positioned as the starting point for measuring the length of the cervix on MRI images. On dynamic contrast-enhanced MRI (DCE-MRI), the section formed by the enhancement difference between the uterus and cervix, and on T2-weighted imaging(T2WI), the section formed by the physiological curvature of the uterus and the low signal intensity of the cervical stroma were used as starting points. The results showed no statistically significant difference compared with the removed uterus specimens (p = 0.208, p = 0.571, p = 0.804). A history of cesarean section(p < 0.001), irregular vaginal bleeding for more than three months(p < 0.001), cervical adenomyosis(p = 0.043), and premenopause(p = 0.001) were not conducive to locating the internal os of the cervix by MRI. Our findings provide valuable information and confirm the position of the internal os of the cervix on MRI images, and the several important infuencing factors. We hope that some patients will benefit from our study.

Interleukin-33 promotes intrauterine adhesion formation in mice through the mitogen-activated protein kinase signaling pathway.

IL-33 belongs to the inflammatory factor family and is closely associated with the inflammatory response. However, its role in the development of intrauterine adhesions (IUAs) remains unclear. In this study, the role of IL-33 in the formation of IUAs after endometrial injury was identified via RNA sequencing after mouse endometrial organoids were transplanted into an IUA mouse model. Major pathological changes in the mouse uterus, consistent with the expression of fibrotic markers, such as TGF-ß, were observed in response to treatment with IL-33. This finding may be attributed to activation of the phosphorylation of downstream MAPK signaling pathway components, which are activated by the release of IL-33 in macrophages. Our study provides a novel mechanism for elucidating IUA formation, suggesting a new therapeutic strategy for the prevention and clinical treatment of IUAs.

Generation and Characterization of Rat Uterus Organoids from Rat Endometrial Epithelial Stem Cells.

Endometrial organoids offer valuable insights into the development and pathophysiology of endometrial diseases and serve as platforms for drug testing. While human and mouse endometrial organoids have been developed, research on rat endometrial organoids remains limited. Given that rats can better simulate certain endometrial pathologies, such as intrauterine adhesions, this study aimed to establish rat endometrial organoids. We present a detailed protocol for the isolation and culture of rat endometrial epithelial stem cells (reESCs) and the generation of rat endometrial organoids. Using a refined reESCs expansion medium, we successfully isolated and stably expanded reESCs, demonstrating their long-term culture potential. The reESC-generated organoids exhibited typical structural and functional characteristics of the endometrium, including hormone responsiveness. Our results showed that rat endometrial organoids could be cultured over a long term with stable proliferation, maintaining the glandular structure, cell polarity, and functional characteristics of the endometrial epithelium. This novel rat-derived endometrial organoid model provides a valuable platform for studying endometrial diseases and testing therapeutic interventions, with potential applications across various mammalian species.

Analyses of Neurite and Spine Formation by In Utero Electroporation in Mice.

Dendrite morphology and dendritic spines are key features of the neuronal networks in the brain. Abnormalities in these features have been observed in patients with psychiatric disorders and mouse models of these diseases. In utero electroporation is an easy and efficient gene transfer system for developing mouse embryos in the uterus. By combining with the Cre-loxP system, the morphology of individual neurons can be clearly and sparsely visualized. Here, we describe how this labeling system can be applied to visualize and evaluate the dendrites and dendritic spines of cortical neurons.

Síndrome de Herlyn-Werner Wünderlich: reporte de dos casos / Herlyn-Werner-Wünderlich syndrome: Two case report

El síndrome de Herlyn-Werner Wünderlich, también llamado OHVIRA por sus siglas en inglés (obstructed hemivagina and ipsilateral renal anomaly), es una anomalía congénita mülleriana poco frecuente que se caracteriza por la asociación entre útero didelfo, hemivagina obstruida y agenesia renal ipsilateral. La presentación clínica más común es la masa abdominal secundaria a hematocolpos, dolor y dismenorrea. Se asocia a infertilidad, endometriosis, alteraciones menstruales y obstétricas. La ecografía es la técnica de elección para la evaluación inicial, mientras que la resonancia magnética sigue siendo el método más exacto para el diagnóstico. La septotomía vaginal es el tratamiento recomendado. Se describen 2 casos clínicos con el objetivo de destacar la importancia del diagnóstico temprano para evitar las posibles complicaciones futuras.

Herlyn-Werner-Wunderlich syndrome, also known as obstructed hemivagina and ipsilateral renal anomaly (OHVIRA), is a rare, congenital Müllerian duct anomaly characterized by the association of septate uterus, obstructed hemivagina, and ipsilateral renal agenesis. The most common clinical presentation is an abdominal mass secondary to hematocolpos, pain, and dysmenorrhea. It is associated with infertility, endometriosis, and menstrual and obstetric alterations. The ultrasound is the technique of choice for the initial assessment, while the magnetic resonance imaging remains the most accurate method for diagnosis. The resection of the vaginal septum is the recommended treatment. Here we describe 2 clinical cases to highlight the importance of an early diagnosis to prevent potential complications in the future.

A case of Herlyn-Werner-Wunderlich syndrome with exacerbation of hematometra after adnexectomy.

A 27-year-old nulliparous woman presented with a feeling of fullness in the lower abdomen and abdominal pain. A left ovarian tumor, uterus didelphys, left renal agenesis, and left vaginal atresia were observed on imaging. The ovarian tumor was presumed to have caused the abdominal pain, and an abdominal left adnexectomy was performed. After 3 months, she reported severe lower abdominal pain during menstruation. Transvaginal ultrasonography revealed uterine enlargement. After 17 days, the patient presented with abdominal pain and fever. She was diagnosed with peritonitis due to infection and left uterine hematometra. Because she did not improve with antibiotic treatment, left laparoscopic hysterectomy was performed. Subsequently, she did not experience the lower abdominal pain. Appropriate diagnosis and treatment based on the morphology of the reproductive tract and symptoms must be considered in patients with Herlyn-Werner-Wunderlich syndrome. Treatment must permit the outflow of menstrual blood.

Transplantation of human endometrial perivascular stem cells with hydroxy saffron yellow A promotes uterine repair in rats.

BACKGROUND: Intrauterine adhesions (IUAs) jeopardise uterine function in women, which is a great challenge in the clinic. Previous studies have shown that endometrial perivascular cells (En-PSCs) can improve the healing of scarred uteri and that hydroxysafflor yellow A (HSYA) promotes angiogenesis. The purpose of this study was to observe whether the combination of En-PSCs with HSYA could improve the blood supply and fertility in the rat uterus after full-thickness injury. METHODS: En-PSCs were sorted by flow cytometry, and the effect of HSYA on the proliferation and angiogenesis of the En-PSCs was detected using CCK-8 and tube formation assays. Based on a previously reported rat IUA model, the rat uteri were sham-operated, spontaneously regenerated, or treated with collagen-loaded PBS, collagen-loaded HSYA, collagen-loaded En-PSCs, or collagen-loaded En-PSCs with HSYA, and then collected at both 30 and 90 days postsurgery. HE staining and Masson staining were used to evaluate uterine structure and collagen fibre deposition, and immunohistochemical staining for α-SMA and vWF was used to evaluate myometrial regeneration and neovascularization in each group. A fertility assay was performed to detect the recovery of pregnancy function in each group. RNA-seq was performed to determine the potential mechanism underlying En-PSCs/HSYA treatment. Immunofluorescence, tube formation assays, and Western blot were used to validate the molecular mechanism involved. RESULTS: The transplantation of Collagen/En-PSCs/HSYA markedly promoted uterine repair in rats with full-thickness injury by reducing fibrosis, increasing endometrial thickness, regenerating myometrium, promoting angiogenesis, and facilitated live births. RNA sequencing results suggested that En-PSCs/HSYA activated the NRG1/ErbB4 signaling pathway. In vitro tube formation experiments revealed that the addition of an ErbB inhibitor diminished the tube formation ability of cocultured En-PSCs and HUVECs. Western blot results further showed that elevated levels of NRG1 and ErbB4 proteins were detected in the Collagen/En-PSCs/HSYA group compared to the Collagen/En-PSCs group. These collective results suggested that the beneficial effects of the transplantation of Collagen/En-PSCs/HSYA might be attributed to the modulation of the NRG1/ErbB4 signaling pathway. CONCLUSIONS: The combination of En-PSCs/HSYA facilitated morphological and functional repair in rats with full-thickness uterine injury and may promote endometrial angiogenesis by regulating the NRG1/ErbB4 signaling pathway.

The importance of the 'uterine factor' in recurrent pregnancy loss: a retrospective cohort study on women screened through 3D transvaginal ultrasound.

STUDY QUESTION: What is the prevalence of congenital and acquired anomalies of the uterus in women with recurrent pregnancy loss (RPL) of unknown etiology examined using 3D transvaginal ultrasound (US)? SUMMARY ANSWER: Depending on the adopted diagnostic criteria, the prevalence of partial septate uterus varies between 7% and 14% and a T-shaped uterus is 3% or 4%, while adenomyosis is 23%, at least one of type 0, type 1 or type 2 myoma is 4%, and at least one endometrial polyp is 4%. WHAT IS KNOWN ALREADY: ESHRE and the Royal College of Obstetricians and Gynaecologists guidelines on RPL recommend the adoption of the 3D transvaginal US to evaluate the 'uterine factor'. Nevertheless, there are no published studies reporting the prevalence of both congenital and acquired uterine anomalies as assessed by 3D transvaginal US and diagnosed according to the criteria proposed by the most authoritative panels of experts in a cohort of women with RPL. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study including 442 women with at least two previous first-trimester spontaneous pregnancy losses (i.e. non-viable intrauterine pregnancies), who referred to the obstetrics and gynecology unit of two university hospitals between July 2020 and July 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: Records of eligible women were reviewed. Women could be included in the study if: they were between 25 and 42 years old; they had no relevant comorbidities; they were not affected by infertility, and they had never undergone ART; they and their partner tested negative to a comprehensive RPL diagnostic work-up; and they had never undergone metroplasty, myomectomy, minimally invasive treatments for uterine fibroids or adenomyomectomy. Expert sonographers independently re-analyzed the stored 2- and 3D transvaginal US images of all included patients. Congenital uterine anomalies (CUAs) were reported according to the American Society for Reproductive Medicine (ASRM) 2021, the ESHRE/European Society for Gynaecological Endoscopy (ESGE) and the Congenital Uterine Malformation by Experts (CUME) criteria. Acquired uterine anomalies were reported according to the International Federation of Gynecology and Obstetrics (FIGO) and the Morphological Uterus Sonographic Assessment (MUSA) criteria. MAIN RESULTS AND THE ROLE OF CHANCE: The partial septate uterus was diagnosed in 60 (14%; 95% CI: 11-17%), 29 (7%; 95% CI: 5-9%), and 47 (11%; 95% CI: 8-14%) subjects, according to the ESHRE/ESGE, the ASRM 2021, and the CUME criteria, respectively. The T-shaped uterus was diagnosed in 19 women (4%; 95% CI: 3-7%) according to the ESHRE/ESGE criteria and in 13 women (3%; 95% CI: 2-5%) according to the CUME criteria. The borderline T-shaped uterus (diagnosed when two out of three CUME criteria for T-shaped uterus were met) was observed in 16 women (4%; 95% CI: 2-6%). At least one of FIGO type 0, type 1, or type 2 myoma was detected in 4% of included subjects (95% CI: 3-6%). Adenomyosis was detected in 100 women (23%; 95% CI: 19-27%) and was significantly more prevalent in women with primary RPL and in those with three or more pregnancy losses. At least one endometrial polyp was detected in 4% of enrolled women (95% CI: 3-7%). LIMITATIONS, REASONS FOR CAUTION: The absence of a control group prevented us from investigating the presence of an association between both congenital and acquired uterine anomalies and RPL. Second, the presence as well as the absence of both congenital and acquired uterine anomalies detected by 3D US was not confirmed by hysteroscopy. Finally, the results of the present study inevitably suffer from the intrinsic limitations of the adopted classification systems. WIDER IMPLICATIONS OF THE FINDINGS: The prevalence of CUAs in women with RPL varies depending on the classification system used. For reasons of clarity, the US reports should always state the name of the uterine anomaly as well as the adopted classification and diagnostic criteria. Adenomyosis seems to be associated with more severe forms of RPL. The prevalence rates estimated by our study as well as the replicability of the adopted diagnostic criteria provide a basis for the design and sample size calculation of prospective studies. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was used. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Injectable, degradable, and mechanically adaptive hydrogel induced by L-serine and allyl-functionalized chitosan with platelet-rich plasma for treating intrauterine adhesions.

The integration of barrier materials with pharmacological therapy is a promising strategy to treat intrauterine adhesions (IUAs). However, most of these materials are surgically implanted in a fixed shape and incongruence with the natural mechanical properties of the uterus, causing poor adaptability and significant discomfort to the patients. Herein, an injectable, biodegradable, and mechanically adaptive hydrogel loaded with platelet-rich plasma (PRP) is created by L­serine and allyl functionalized chitosan (ACS) to achieve efficient, comfortable, and minimally invasive treatment of IUAs. L­serine induces fast gelation and mechanical reinforcement of the hydrogel, while ACS introduces, imparting a good injectability and complaint yet strong feature to the hydrogel. This design enables the hydrogel to adapt to the complex geometry and match the mechanical properties of the uterine. Moreover, the hydrogel exhibits proper degradability, sustained growth factors (GFs) of PRP release ability, and good biocompatibility. Consequently, the hydrogel shows promising therapeutic efficacy by reducing collagen fiber deposition and facilitating endometrium cell proliferation, thereby restoring the fertility function of the uterus in an IUAs model of rats. Accordingly, the combination of L­serine and ACS-induced hydrogel with such advantages holds great potential for treating IUAs. STATEMENT OF SIGNIFICANCE: This research introduces a breakthrough in the treatment of intrauterine adhesions (IUAs) with an injectable, biodegradable and mechanically adaptive hydrogel using L­serine and allyl functionalized chitosan (ACS). Unlike traditional surgical treatments, this hydrogel uniquely conforms to the uterus's geometry and mechanical properties, offering a minimally invasive, comfortable, and more effective solution. The hydrogel is designed to release growth factors from platelet-rich plasma (PRP) sustainably, promoting tissue regeneration by enhancing collagen fiber deposition and endometrium cell proliferation. Demonstrated efficacy in a rat model of IUAs indicates its great potential to significantly improve fertility restoration treatments. This advancement represents a significant leap in reproductive medicine, promising to transform IUAs treatment with its innovative approach to achieving efficient, comfortable, and minimally invasive therapy.

Transcription Factor 23 is an Essential Determinant of Murine Term Parturition.

Pregnancy involving intricate tissue transformations governed by the progesterone hormone (P4). P4 signaling via P4 receptors (PRs) is vital for endometrial receptivity, decidualization, myometrial quiescence, and labor initiation. This study explored the role of TCF23 as a downstream target of PR during pregnancy. TCF23 was found to be expressed in female reproductive organs, predominantly in uterine stromal and smooth muscle cells. Tcf23 expression was high during midgestation and was specifically regulated by P4, but not estrogen. The Tcf23 knockout (KO) mouse was generated and analyzed. Female KO mice aged 4-6 months exhibited subfertility, reduced litter size, and defective parturition. Uterine histology revealed disrupted myometrial structure, altered collagen organization, and disarrayed smooth muscle sheets at the conceptus sites of KO mice. RNA-Seq analysis of KO myometrium revealed dysregulation of genes associated with cell adhesion and extracellular matrix organization. TCF23 potentially modulates TCF12 activity to mediate cell-cell adhesion and matrix modulation in smooth muscle cells. Overall, TCF23 deficiency leads to impaired myometrial remodeling, causing parturition delay and fetal demise. This study sheds light on the critical role of TCF23 as a dowstream mediator of PR in uterine remodeling, reflecting the importance of cell-cell communication and matrix dynamics in myometrial activation and parturition.

Silkworm (Bombyx mori L.) Has Beneficial Effects on Menopausal Symptoms by Enhancing Estrogen Receptor Signaling in Ovariectomized Mice.

Existing hormone replacement therapy for menopause has drawbacks, necessitating new treatment agents. Silkworms have demonstrated estrogenic properties, offering promising alternatives. We assessed the therapeutic effects of freeze-dried silkworm powder (SWP) on menopausal symptoms using an ovariectomized (OVX) mouse model. The experimental design comprised a sham surgery group (Sham), an OVX control group, a low-dose SWP group post-OVX (80 mg/kg, OVX-SWP-L), a high-dose SWP group post-OVX (160 mg/kg, OVX-SWP-H), and an estradiol treatment group post-OVX (OVX-E2). Treatments were administered orally thrice weekly over eight weeks; body weight was monitored weekly. The SWP-treated groups (SWP-L and SWP-H) exhibited less weight gain and increased uterine thickness than the OVX control. Molecular analyses demonstrated that SWP significantly enhanced the phosphorylation of estrogen receptor alpha (ERα), ERK, and AKT. Furthermore, biochemical assays revealed reduced serum neutral lipids across all SWP treatment groups. Notably, HDL-cholesterol levels were significantly increased in the SWP-L group compared to the OVX group. Serum estradiol concentrations were elevated in all the SWP groups, with significant increases in the high-dose group. These findings indicate that SWP may promote the activation of estrogen receptor signaling and improve symptoms associated with estrogen deficiency during menopause.

Uterine changes in transgender men receiving testosterone therapy.

OBJECTIVES: Despite regular gender-affirming hormone therapy (GAHT), the presence of uterine bleeding can occur occasionally and cause profound discomfort. This study aimed to evaluate the histologic features and immunohistochemical expression of estrogen (ER), progesterone (PR), and androgen receptors (AR) in the endometrium and myometrium of transgender men receiving testosterone therapy and relate them to clinical and hormonal characteristics. DESIGN: Retrospective cross-sectional study. METHODS: Thirty-four transgender men undergoing gender-affirming surgery were included. Clinical, sociodemographic, and laboratory data as well as anatomopathological and immunohistochemical findings were evaluated. RESULTS: The participants' mean age was 42.35 (SD, 10.00) years, and body mass index was 28.16 (SD, 5.52) kg/m2. The mean GAHT duration before surgery was 5.36 (SD, 3.24) years. The mean testosterone levels were 814.98 (SD, 407.13) ng/dL, and estradiol levels were 55.22 (SD, 25.27) pg/mL. The endometrium was atrophic in 61.8%, proliferative in 17.6%, and secretory in 20.6%. Immunohistochemical receptor analysis revealed that endometrial epithelial cells expressed ER (90%) and PR (80%), with a lower expression of AR (30%). In stromal tissue, the median ER, PR, and AR expression was lower than that in the epithelium (60%, 70%, and 25%, respectively). The myometrium showed high expression of PR (90%) and ER (70%), with the highest expression of AR (65%) being localized to this region. CONCLUSIONS: In the present study, GAHT induced an atrophic condition of the endometrium in two-thirds of the transgender men, with a limited AR expression in the endometrial region. The present results suggest that testosterone-based GAHT for a mean of 5 years is safe in transgender men achieving amenorrhea.

Development and validation of a deep learning-based method for automatic measurement of uterus, fibroid, and ablated volume in MRI after MR-HIFU treatment of uterine fibroids.

INTRODUCTION: The non-perfused volume divided by total fibroid load (NPV/TFL) is a predictive outcome parameter for MRI-guided high-intensity focused ultrasound (MR-HIFU) treatments of uterine fibroids, which is related to long-term symptom relief. In current clinical practice, the MR-HIFU outcome parameters are typically determined by visual inspection, so an automated computer-aided method could facilitate objective outcome quantification. The objective of this study was to develop and evaluate a deep learning-based segmentation algorithm for volume measurements of the uterus, uterine fibroids, and NPVs in MRI in order to automatically quantify the NPV/TFL. MATERIALS AND METHODS: A segmentation pipeline was developed and evaluated using expert manual segmentations of MRI scans of 115 uterine fibroid patients, screened for and/or undergoing MR-HIFU treatment. The pipeline contained three separate neural networks, one per target structure. The first step in the pipeline was uterus segmentation from contrast-enhanced (CE)-T1w scans. This segmentation was subsequently used to remove non-uterus background tissue for NPV and fibroid segmentation. In the following step, NPVs were segmented from uterus-only CE-T1w scans. Finally, fibroids were segmented from uterus-only T2w scans. The segmentations were used to calculate the volume for each structure. Reliability and agreement between manual and automatic segmentations, volumes, and NPV/TFLs were assessed. RESULTS: For treatment scans, the Dice similarity coefficients (DSC) between the manually and automatically obtained segmentations were 0.90 (uterus), 0.84 (NPV) and 0.74 (fibroid). Intraclass correlation coefficients (ICC) were 1.00 [0.99, 1.00] (uterus), 0.99 [0.98, 1.00] (NPV) and 0.98 [0.95, 0.99] (fibroid) between manually and automatically derived volumes. For manually and automatically derived NPV/TFLs, the mean difference was 5% [-41%, 51%] (ICC: 0.66 [0.32, 0.85]). CONCLUSION: The algorithm presented in this study automatically calculates uterus volume, fibroid load, and NPVs, which could lead to more objective outcome quantification after MR-HIFU treatments of uterine fibroids in comparison to visual inspection. When robustness has been ascertained in a future study, this tool may eventually be employed in clinical practice to automatically measure the NPV/TFL after MR-HIFU procedures of uterine fibroids.

Determination of the impacts of supplemental dietary curcumin on post-partum uterine involution using pulsed-wave doppler ultrasonography in Zaraibi goat.

This study aimed to evaluate the impacts of supplemental dietary curcumin on post-partum uterine involution using pulsed-wave Doppler ultrasonography in postpartum goats. Ten pluriparous Zaraibi goats were used and divided into two groups. Group 1 (n = 5; control) received only a base diet. Group 2 (n = 5; treated) received a base diet supplemented with curcumin (200 mg/kg diet) daily for 28 days, starting from day 1 postpartum (PP) till day 28 PP. Uterine morphometrical changes (uterine horn diameter; UHD and caruncle diameter; CD), uterine hemodynamics (resistance and pulsatility indices (RI and PI), systolic/ diastolic ratio (S/D), peak systolic velocity (PSV), end-diastolic velocity (EDV), blood flow volume (BFV), and blood flow rate (BFR)), and progesterone level were evaluated. Results revealed that the diameter of the uterine horn decreased rapidly from day 1 to day 10 PP (> 50%) but more steadily from day 14 to day 28 PP in both groups. After day 21 PP, there was nearly no reduction in UHD and CD in both groups. The treated group had lower values of the RI and PI (P < 0.05) than the control group. Regarding the BFR and BFV in the treated group, there was a significant increase (P < 0.05) on day 17 PP, then started to decrease till day 28 PP. While in the control group, there was a significant decrease (P < 0.05) in BFR and BFV from day 1 PP till day 28 PP. In conclusion, the incorporation of curcumin in the diet of PP Zaraibi goats improved reproductive performance via improvements in uterine morphometric changes as well as blood perfusion.