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Biomolecules Apr 2024Hydrogen sulfide (HS), previously regarded as a toxic exhaust and atmospheric pollutant, has emerged as the third gaseous signaling molecule following nitric oxide (NO)... (Review)
Review
Hydrogen sulfide (HS), previously regarded as a toxic exhaust and atmospheric pollutant, has emerged as the third gaseous signaling molecule following nitric oxide (NO) and carbon monoxide (CO). Recent research has revealed significant biological effects of HS in a variety of systems, such as the nervous, cardiovascular, and digestive systems. Additionally, HS has been found to impact reproductive system function and may have therapeutic implications for reproductive disorders. This paper explores the relationship between HS and male reproductive disorders, specifically erectile dysfunction, prostate cancer, male infertility, and testicular damage. Additionally, it examines the impact of HS regulation on the pathophysiology of the female reproductive system, including improvements in preterm birth, endometriosis, pre-eclampsia, fetal growth restriction, unexplained recurrent spontaneous abortion, placental oxidative damage, embryo implantation, recovery of myometrium post-delivery, and ovulation. The study delves into the regulatory functions of HS within the reproductive systems of both genders, including its impact on the NO/cGMP pathway, the activation of K channels, and the relaxation mechanism of the spongy smooth muscle through the ROCK pathway, aiming to broaden the scope of potential therapeutic strategies for treating reproductive system disorders in clinical settings.
Topics: Hydrogen Sulfide; Humans; Female; Male; Pregnancy; Animals; Nitric Oxide; Reproduction
PubMed: 38785947
DOI: 10.3390/biom14050540 -
Journal of Physiological Investigation Mar 2024Uterine adenomyosis is an estrogen-dependent chronic inflammatory condition and may cause painful symptoms, abnormal uterine bleeding, and/or subfertility/infertility.... (Review)
Review
Uterine adenomyosis is an estrogen-dependent chronic inflammatory condition and may cause painful symptoms, abnormal uterine bleeding, and/or subfertility/infertility. It is characterized by the presence of endometrial glands and stroma within the myometrium causing enlargement of the uterus as a result of reactive hyperplastic and/or hypertrophic change of the surrounding myometrium. Similar to endometriosis, adenomyosis has a negative impact on female fertility. Abnormal uterotubal sperm transport, tissue inflammation, and the toxic effect of chemical mediators have been proposed as contributing factors. Inflammation-induced damage of the mucosal cilia in the fallopian tube has been reported. Besides other proposed mechanisms, our most recent study with transmission electron microscopy analysis indicated that microvilli damage and an axonemal alteration in the apical endometria occur in response to endometrial inflammation. This may be involved in the negative fertility outcome in women with adenomyosis. We present a critical analysis of the literature data concerning the mechanistic basis of infertility in women with adenomyosis and its impact on fertility outcome.
Topics: Humans; Female; Adenomyosis; Infertility, Female; Endometrium; Cilia
PubMed: 38780290
DOI: 10.4103/ejpi.EJPI-D-24-00032 -
Cureus Apr 2024Struma ovarii is a monodermal teratoma characterized by the presence of >50% thyroid tissue. It is mostly benign; therefore, preoperative diagnosis is important. It...
Struma ovarii is a monodermal teratoma characterized by the presence of >50% thyroid tissue. It is mostly benign; therefore, preoperative diagnosis is important. It usually manifests as a multilocular cystic mass but rarely as a predominantly solid mass. On magnetic resonance imaging (MRI), solid-appearing struma ovarii showed early signal intensity enhancement on dynamic gadolinium-enhanced T1-weighted images, which histopathologically indicates the presence of thyroid tissue with abundant blood vessels. The Ovarian-Adnexal Reporting and Data System (O-RADS) MRI score is a validated classification worldwide for characterizing adnexal lesions. Based on the morphology, signal intensity, and enhancement of any solid tissue on the MRI, the scoring system can be used to classify adnexal lesions into five categories from score one (no adnexal mass) to score five (high risk of malignancy). An adnexal solid mass with a higher signal intensity than that of the myometrium 30-40 seconds after gadolinium (Gd) injection on non-dynamic contrast-enhanced (non-DCE) MRI was assigned a score of 5 (high risk of malignancy). We present a case of solid-appearing struma ovarii with a higher signal intensity than that of the myometrium 30 seconds after Gd injection on non-DCE MRI, and it was classified as score five preoperatively. Therefore, a total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed despite the presence of a benign ovarian mass. When an adnexal mass with a higher signal intensity than that of the myometrium 30-40 seconds after Gd injection on non-DCE MRI is encountered, struma ovarii should be included in the differential diagnosis, despite the O-RADS MRI score of five and management of the situation should be discussed.
PubMed: 38741801
DOI: 10.7759/cureus.58176 -
Acta Radiologica Open May 2024Uterine cavity pathology may affect the endometrium or myometrium, resulting in distortion of the uterine cavity, and is responsible for 2%-5% of infertility. The...
BACKGROUND
Uterine cavity pathology may affect the endometrium or myometrium, resulting in distortion of the uterine cavity, and is responsible for 2%-5% of infertility. The methods for its assessment usually involve imaging modalities like pelvic ultrasonography, often transvaginal-(TVS), and hysterosalpingography-(HSG), with hysteroscopy-(HSC) as the gold standard. However, HSC is not readily available in resource-poor-settings.
PURPOSE
To determine and compare the diagnostic accuracy of TVS and HSG in detecting uterine cavity pathology using HSC as a gold standard.
MATERIALS AND METHODS
A cross-sectional analytical study of consenting infertile women for evaluation of the uterine cavity using transvaginal-ultrasonography, hysterosalpingogram, and hysteroscopy. The primary-outcome-measures were the sensitivity, specificity, and accuracy of TVS and HSG in detecting uterine cavity abnormalities using HSG as the gold standard.
RESULTS
Eighty-eight participants were analysed for this study. The lesions confirmed on HSC were intrauterine-adhesions (43.1%), endometrial polyps (14.8%), submucous fibroids (18.2%), intrauterine-septum (13.6%), and cavity distortion (14.8%). The overall sensitivity with TVS was 57.7%, with a specificity of 97.6%, a positive-predictive-value (PPV) of 88.2%, and a negative-predictive-value (NPV) of 88.2%, giving a percentage-accuracy of 88.2%. In comparison, HSG had a sensitivity of 72.1%, a specificity of 99.4%, a PPV of 97.4%, and an NPV of 92.0%, giving an overall accuracy of 92.9%. The detection rates of TVS and HSG in this category were: fibroids (97.7% vs 89.8%; = .0004) and adhesions (73.9% vs 87.5%; = .0002), respectively.
CONCLUSION
HSG appears to be the superior modality for detection of obliterative uterine cavity pathologies, while TVS is better suited for myometrium and endometrial lesions.
PubMed: 38737559
DOI: 10.1177/20584601241252335 -
Journal of Multidisciplinary Healthcare 2024The objective of this study was to investigate the risk factors associated with cesarean scar pregnancy (CSP) and to develop a model for predicting intraoperative...
OBJECTIVE
The objective of this study was to investigate the risk factors associated with cesarean scar pregnancy (CSP) and to develop a model for predicting intraoperative bleeding risk.
METHODS
We retrospectively analyzed the clinical data of 208 patients with CSP who were admitted to the People's Hospital of Leshan between January 2018 and December 2022. Based on whether intraoperative bleeding was ≥ 200 mL, we categorized them into two groups for comparative analysis: the excessive bleeding group (n = 27) and the control group (n = 181). Identifying relevant factors, we constructed a prediction model and created a nomogram.
RESULTS
We observed that there were significant differences between the two groups in several parameters. These included the time of menstrual cessation ( = 0.002), maximum diameter of the gestational sac ( < 0.001), thickness of the myometrium at the uterine scar ( = 0.001), pre-treatment blood HCG levels ( = 0.016), and the grade of blood flow signals ( < 0.001). We consolidated the above data and constructed a clinical prediction model. The model exhibited favorable results in terms of predictive efficacy, discriminative ability (C-index = 0.894, specificity = 0.834, sensitivity = 0.852), calibration precision (mean absolute error = 0.018), and clinical decision-making utility, indicating its effectiveness.
CONCLUSION
The clinical prediction model related to the risk of hemorrhage that we developed in this experiment can assist in the development of appropriate interventions and effectively improve patient prognosis.
PubMed: 38716371
DOI: 10.2147/JMDH.S458968 -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... Apr 2024To explore the pathogenic roles of miR-21, estrogen (E2), and estrogen receptor (ER) in adenomyosis.
OBJECTIVE
To explore the pathogenic roles of miR-21, estrogen (E2), and estrogen receptor (ER) in adenomyosis.
METHODS
We examined the expression levels of miR-21 in specimens of adenomyotic tissue and benign cervical lesions using qRT-PCR. In primary cultures of cells isolated from the adenomyosis lesions, the effect of ICI82780 (an ER inhibitor) on miR-21 expression levels prior to E2 activation or after E2 deprivation were examined with qRT-PCR. We further assessed the effects of a miR-21 mimic or an inhibitor on proliferation, apoptosis, migration and autophagy of the cells.
RESULTS
The expression level of miR-21 was significantly higher in adenomyosis tissues than in normal myometrium ( < 0.05). In the cells isolated from adenomyosis lesions, miR-21 expression level was significantly higher in E2 activation group than in ER inhibition + E2 activation group and the control group ( < 0.05); miR-21 expression level was significantly lower in cells in E2 deprivation+ER inhibition group than in E2 deprivation group and the control group ( < 0.05). The adenomyosis cells transfected with miR-21 inhibitor showed inhibited proliferation and migration, expansion of mitochondrial endoplasmic reticulum, increased lysosomes, presence of autophagosomes, and increased cell apoptosis, while transfection of the cells with the miR-21 mimic produced the opposite effects.
CONCLUSION
MiR-21 plays an important role in promoting proliferation, migration, and antiapoptosis in adenomyosis cells by altering the cell ultrastructure, which may contribute to early pathogenesis of the disease. In addition to binding with E2, ER can also regulate miR-21 through other pathways to participate in the pathogenesis of adenomyosis, thus having a stronger regulatory effect on miR-21 than E2.
Topics: Humans; MicroRNAs; Female; Adenomyosis; Cell Proliferation; Apoptosis; Estrogens; Autophagy; Cell Movement; Receptors, Estrogen; Myometrium
PubMed: 38708494
DOI: 10.12122/j.issn.1673-4254.2024.04.02 -
Medicina (Kaunas, Lithuania) Apr 2024: Wound healing encompasses a multitude of factors and entails the establishment of interactions among components of the basement membrane. The quantification of...
: Wound healing encompasses a multitude of factors and entails the establishment of interactions among components of the basement membrane. The quantification of particle concentrations can serve as valuable biomarkers for assessing biomechanical muscle properties. The objective of this study was to examine the immunoexpression and immunoconcentration of myometrial collagen type VI, elastin, alpha-smooth muscle actin, and smooth muscle myosin heavy chain, as well as the expression of platelets and clusters of differentiation 31 in the uterine scar following a cesarean section (CS). : A total of 177 biopsies were procured from a cohort of pregnant women who were healthy, specifically during the surgical procedure of CS. The participants were categorized into seven distinct groups. Group 1 consisted of primiparas, with a total of 52 individuals. The subsequent groups were organized based on the duration of time that had elapsed since their previous CS. The analysis focused on the immunoexpression and immunoconcentration of the particles listed. : No significant variations were observed in the myometrial immunoconcentration of collagen type VI, elastin, smooth muscle myosin, and endothelial cell cluster of differentiation 31 among the analyzed groups. The concentration of alpha-smooth muscle actin in the myometrium was found to be significantly higher in patients who underwent CS within a period of less than 2 years since their previous CS, compared to those with a longer interval between procedures. : Our findings indicate that the immunoconcentration of uterine myometrial scar collagen type VI, elastin, smooth muscle myosin heavy chain, alpha-smooth muscle actin, and endothelial cell marker cluster of differentiation 31 remains consistent regardless of the duration elapsed since the previous CS. The findings indicate that there are no significant alterations in the biomechanical properties of the uterine muscle beyond a period of 13 months following a CS.
Topics: Humans; Female; Cesarean Section; Cicatrix; Adult; Immunohistochemistry; Pregnancy; Myometrium; Actins; Elastin; Biomarkers; Wound Healing; Cohort Studies
PubMed: 38674297
DOI: 10.3390/medicina60040651 -
PloS One 2024Endometrial cancer is the most prevalent gynecologic malignancy with a high risk of recurrence. Local recurrence occurs in 7-20% of patients with treated stage I cancer...
Endometrial cancer is the most prevalent gynecologic malignancy with a high risk of recurrence. Local recurrence occurs in 7-20% of patients with treated stage I cancer within 3 years after primary treatment. In this study, we found significantly elevated mRNA expression levels of the oncoprotein KRAS, along with two replicative stress markers, ATR and CHEK1, in samples of endometrial carcinomas of endometrium (ECE) from patients with relapse. In contrast, mRNA expression levels of the studied genes were low and uniform in samples from patients without relapse. Elevated levels of KRAS protein and the phosphorylated form of ATR/CHEK1 were distinguishing features of recurrent ECE. A strong positive correlation was found between elevated mRNA and protein levels of the studied molecules. Elevated KRAS protein levels are characteristic of poorly differentiated (G3) endometrial carcinomas with deep myometrial invasion in patients without recurrence. In contrast, in patients with recurrence, higher protein levels of KRAS, pATR and pCHEK1 were observed in samples of G1-2 endometrial carcinomas, with statistically significant differences confirmed for pATR. High pCHEK1 protein levels are associated with deep tumor invasion in the myometrium among patients with recurrence. ROC analysis confirmed that evaluating the specificity and sensitivity of KRAS, pATR and pCHEK1 predicts recurrence development in patients with ECE. Our findings indicate that markers of replicative stress may play a significant role in ECE pathogenesis. Determining their levels in tumor samples after primary treatment could help define patients at high risk of recurrence and guide consequent courses of treatment.
Topics: Humans; Female; Endometrial Neoplasms; Proto-Oncogene Proteins p21(ras); Middle Aged; Checkpoint Kinase 1; Ataxia Telangiectasia Mutated Proteins; Neoplasm Recurrence, Local; Risk Factors; Aged; ras Proteins; Gene Expression Regulation, Neoplastic; Adult; Biomarkers, Tumor; RNA, Messenger; Proto-Oncogene Proteins
PubMed: 38669256
DOI: 10.1371/journal.pone.0302075 -
BioRxiv : the Preprint Server For... Apr 2024Estradiol (E2) and relaxin (Rln) are steroid and polypeptide hormones, respectively, with important roles in the female reproductive tract, including myometrium. Some...
Estradiol (E2) and relaxin (Rln) are steroid and polypeptide hormones, respectively, with important roles in the female reproductive tract, including myometrium. Some actions of Rln, which are mediated by its membrane receptor RXFP1, require or are augmented by E2 signaling through its cognate nuclear steroid receptor, estrogen receptor alpha (ERα). In contrast, other actions of Rln act in opposition to the effects of E2. Here we explore the molecular and genomic mechanisms that underlie the functional interplay between E2 and Rln in the myometrium. We used both ovariectomized female mice and immortalized human myometrial cells expressing wild type or mutant ERα (hTERT-HM-ERα cells). Our results indicate that Rln attenuates the genomic actions and biological effects of estrogen in the myometrium and myometrial cells by reducing phosphorylation ERα on serine 118 (S118). Interestingly, we observed a potent inhibitory effect of Rln on the E2-dependent binding of ERα across the genome. The reduction in ERα binding was associated with changes in the hormone-regulated transcriptome, including a decrease in the E2-dependent expression of neighboring genes. The inhibitory effects of Rln cotreatment on the E2-dependent phosphorylation of ERα required the nuclear dual-specificity phosphatases DUSP1 and DUSP5. Moreover, the inhibitory effects of Rln were reflected in a concomitant inhibition of the E2-dependent contraction of myometrial cells. Collectively, our results identify a pathway that integrates Rln/RXFP1 and E2/ERα signaling, resulting in a convergence of membrane and nuclear signaling pathways to control genomic and biological outcomes.
PubMed: 38659934
DOI: 10.1101/2024.04.15.589654