Cyclic ADP-ribose (cADPR) has emerged as a calcium-regulating second messenger in smooth muscle cells. CD38 protein possesses ADP-ribosyl cyclase and cADPR hydrolase activities and mediates cADPR synthesis and degradation. We have previously shown that CD38 expression is regulated by estrogen and progesterone in the myometrium. Considering hormonal regulation in gestation, the objective of the present study was to determine the role of CD38/cADPR signaling in the regulation of intracellular calcium upon contractile agonist stimulation using immortalized pregnant human myometrial (PHM1) cells. Western blot, immunofluorescence, and biochemical studies confirmed CD38 expression and the presence of ADP-ribosyl cyclase (2.6 ± 0.1 pmol/mg) and cADPR hydrolase (26.8 ± 6.8 nmoles/mg/h) activities on the PHM1 cell membrane. Oxytocin, PGF2α, and ET-1 elicited [Ca2+]i responses, and 8-Br-cADPR, a cADPR antagonist significantly attenuated agonist-induced [Ca2+]i responses between 20% and 46% in average. The findings suggest that uterine contractile agonists mediate their effects in part through CD38/cADPR signaling to increase [Ca2+]i and presumably uterine contraction. As studies in humans are limited by the availability of myometrium from healthy donors, PHM1 cells form an in vitro model to study human myometrium.

UNASSIGNED: Focused ultrasound ablation surgery (FUAS) has been widely employed to treat patients with uterine fibroid (UF). This study aimed to estimate myometrial stiffness changes in patients who received FUAS for UFs or myomectomy (ME) and compare the recovery of surrounding myometrium between FUAS and ME groups. Our results may provide more evidence for guiding the proper conception timing in patients with UF.
UNASSIGNED: This study enrolled 173 patients from May 2022 to August 2023. Shear wave elastography (SWE) was used to dynamically monitor myometrial elasticity changes in patients before and after surgery. Moreover, our study monitored and analyzed the stiffness changes in the targeted fibroid after FUAS, as well as in the myometrium around after FUAS or ME.
UNASSIGNED: The stiffness of the myometrium around the resected fibroid was significantly higher than at the preoperative level until 6 months. Conversely, the stiffness of the surrounding myometrium was only temporarily increased 1 day after FUAS. The comparison between FUAS and ME groups regarding the stiffness of the surrounding myometrium showed that nonsignificant differences were detected between the two groups before the treatment. The stiffness of the surrounding myometrium in the ME group was statistically significantly higher than that of the FUAS group 1 day as well as 1, 3, and 6 months after the treatment, respectively.
UNASSIGNED: The FUAS had less impact on the surrounding myometrium than the ME, which may be more conducive to the recovery of myometrial elasticity in patients with UF.

Endometritis and metritis are common reproductive diseases in domestic animals, causing a reduction in reproductive performance and economic losses. A previous study revealed the alterations in the transcriptome of the inflamed porcine endometrium. Data on molecular signatures in the myometrium under inflammatory conditions are limited. The current study analyzed the transcriptomic profile of porcine myometrium after intrauterine Escherichia coli (E.coli) administration. On day 3 of the estrous cycle (Day 0 of the study), 50 ml of either saline (group CON, n = 7) or E. coli suspension (109 colony-forming units/ml, group E. coli, n = 5) were injected into each uterine horn. After eight days, the gilts were euthanized, and the uteri were removed for further analysis. In the myometrium of the CON group versus the E. coli group, microarray analysis revealed 167 differentially expressed genes (DEGs, 78 up- and 89 down-regulated). After intrauterine E. coli administration, among the DEGs of the inflammatory response set, the highest expressed were mRNA for CXCL6, S100A8, S100A12, SLC11A1, S100A9, CCL15, CCR1, CD163, THBS1 and SOCS3, while the most suppressed was mRNA expression for FFAR4, KL, SLC7A2 and MOAB. Furthermore, a comparison of the present results on myometrial transcriptome with the authors\' earlier published data on the endometrial transcriptome shows the partial differences in mRNA expression between both layers after intrauterine E.coli injections. This study, for the first time, presents changes in the transcriptome of porcine myometrium after intrauterine E.coli administration, which may be important for myometrial homeostasis and functions and, as a result, for the uterine inflammation course. Data provide a valuable resource for further studies on genes and pathways regulating uterine inflammation and functions.

Microplastics (MPs) pollution has received widespread attention in recent years as the use of plastics continues to increase. However, currently no studies have reported the finding of MPs in human uterine fibroids (UFs) and myometrium tissues. In this study, UFs tissues (n = 48) and myometrium tissues (n = 40) from 48 patients and myometrium tissues (n = 8) from healthy population were collected. Following digestion of the samples by 10% KOH and 30% H2O2, MPs were analyzed qualitatively and quantitatively using Raman spectroscopy. The 16 UFs and myometrium tissue samples contained an average of 1.5 ± 1.17 MP particles per gram of tissue. Notably, the abundance of MPs in the UFs tissues (2.13 ± 1.17 particles per gram) was higher than in the myometrium tissues (0.88 ± 0.78 particles per gram). In the same cohort of individuals with UFs, the quantities of MPs detected in the affected UFs tissue (2.63 ± 1.77 particles per gram) exceeded those detected in healthy tissue (1.08 ± 0.93 particles per gram), particularly in elderly patients. A correlation was observed between elevated MP levels and frequent consumption of takeout meals and bottled water among patients, indicating that MP ingestion through food sources might have contributed to the increased abundance and variety of MPs within UFs. Furthermore, UFs increased in size with higher concentrations of MPs, which may have been related to elevated levels of MPs-induced hormones. This study provides new insights into the assessment of the relationship between exposure to MPs and human disease risk.

暂无摘要。

Pregnant individuals with obesity (body mass index, BMI ≥ 30 kg/m2) are more likely to experience prolonged labor and have double the risk of cesarean compared with individuals with normal weight (BMI < 25 kg/m2). The aim of this study was to evaluate whether obesity in pregnancy is associated with reduced spontaneous and oxytocin-stimulated myometrial contractile activity using ex vivo preparations. We also assessed the relationship between maternal BMI and the expression of oxytocin (OXTR) and prostaglandin (FP) receptors in the myometrial tissue. We enrolled 73 individuals with a singleton gestation undergoing scheduled cesarean delivery at term in a prospective cohort study. This included 49 individuals with a pre-pregnancy BMI ≥ 30 kg/m2 and 24 with BMI < 25.0 kg/m2. After delivery, a small strip of myometrium was excised from the upper edge of the hysterotomy. Baseline spontaneous and oxytocin stimulated myometrial contractile activity was measured using ex vivo preparations. Additionally, expression of oxytocin and prostaglandin receptors from myometrial samples were compared using qRT-PCR and western blot techniques. Spontaneous and oxytocin-stimulated contraction frequency, duration, and force were not significantly different in myometrial samples from the obese and normal-weight individuals. Myometrial OXTR gene and protein expression was also similar in the two groups. While FP gene expression was lower in the myometrial samples from the obese group, protein expression did not differ. These data help to address an important knowledge gap related to the biological mechanisms underlying the association between maternal obesity and dysfunctional labor.

Angioleiomyoma is an uncommon benign neoplasm of mesenchymal origin that arises from perivascular smooth muscle cells. This soft tissue neoplasm usually occurs in the dermal or subcutaneous tissues of the extremities, head and neck, or trunk with fewer than 40 reported angioleiomyomas arising in the uterine corpus. Herein we report a uterine angioleiomyoma in a 44-year-old G5P4 Hispanic woman with a longstanding history of recurrent abdominal pain, pelvic organ prolapse, abnormal uterine bleeding, anemia, and hypertension. The patient underwent surgical treatment with total laparoscopic hysterectomy with bilateral salpingectomy and a uterosacral ligament suspension. Uterine angioleiomyoma was diagnosed post-operatively based on gross and microscopic features. The location of the uterine angioleiomyoma within the myometrium corresponded with contrast enhancement apparent on preoperative imaging. This and other uterine angioleiomyomas have characteristic imaging, macroscopic, and microscopic features which distinguish it from leiomyoma. Enhancing awareness of this underrecognized entity will facilitate precise diagnosis and thereby enable improved understanding of the clinicopathological characteristics of uterine angioleiomyoma.

OBJECTIVE: 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.
METHODS: 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.

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.

Understanding the molecular factors involved in the development of uterine myomas may result in the use of pharmacological drugs instead of aggressive surgical treatment. ANG1, CaSR, and FAK were examined in myoma and peripheral tissue samples taken from women after myoma surgery and in normal uterine muscle tissue samples taken from the control group. Tests were performed using tissue microarray immunohistochemistry. No statistically significant differences in ANG1 expression between the tissue of the myoma, the periphery, and the normal uterine muscle tissue of the control group were recorded. The CaSR value was reduced in the myoma and peripheral tissue and normal in the group of women without myomas. FAK expression was also lower in the myoma and periphery compared to the healthy uterine myometrium. Calcium supplementation could have an effect on stopping the growth of myomas.