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Journal of Animal Science and... Jul 2024Tissue non-specific alkaline phosphatase (TNSALP; encoded by the ALPL gene) has a critical role in the postnatal regulation of phosphate homeostasis, yet how TNSALP...
BACKGROUND
Tissue non-specific alkaline phosphatase (TNSALP; encoded by the ALPL gene) has a critical role in the postnatal regulation of phosphate homeostasis, yet how TNSALP activity and expression are regulated during pregnancy remain largely unknown. This study tested the hypothesis that progesterone (P4) and/or interferon tau (IFNT) regulate TNSALP activity during pregnancy in sheep.
METHODS
In Exp. 1, ewes were bred and received daily intramuscular injections of either corn oil vehicle (CO) or 25 mg progesterone in CO (P4) for the first 8 days of pregnancy and were hysterectomized on either Day 9, 12, or 125 of gestation. In Exp. 2, ewes were fitted with intrauterine catheters on Day 7 of the estrous cycle and received daily intramuscular injections of 50 mg P4 in CO and/or 75 mg progesterone receptor antagonist (RU486) in CO from Days 8 to 15, and twice daily intrauterine injections of either control proteins (CX) or IFNT (25 µg/uterine horn/d) from Days 11 to 15 (treatment groups: P4 + CX; P4 + IFNT; RU486 + P4 + CX; and RU486 + P4 + IFNT) and were hysterectomized on Day 16.
RESULTS
In Exp. 1, endometria from ewes administered P4 had greater expression of ALPL mRNA than ewes administered CO on Day 12. TNSALP activity appeared greater in the epithelia, stratum compactum stroma, and endothelium of the blood vessels in the endometrium and myometrium from ewes administered P4 than ewes administered CO on Day 12. On Day 125, TNSALP activity localized to uterine epithelial and endothelial cells, independent of P4 treatment. TNSALP activity in placentomes appeared greater in P4 treated ewes and was detected in endothelial cells and caruncular tissue in P4 treated but not CO treated ewes. In Exp. 2, endometrial homogenates from ewes administered RU486 + P4 + CX had lower TNSALP activity those for P4 + CX and P4 + IFNT ewes. Immunoreactive TNSALP protein appeared greater in the mid- and deep-glandular epithelia in RU486 + P4 + CX treated ewes as compared to the other treatment groups. Enzymatic activity appeared greater on the apical surface of the deep glandular epithelia in endometria from ewes treated with RU486 + P4 + CX compared to the other treatment groups.
CONCLUSIONS
These results suggest that P4, but not IFNT, regulates the expression and activity of TNSALP in utero-placental tissues and has the potential to contribute to the regulation of phosphate availability that is critical for conceptus development during pregnancy.
PubMed: 38956701
DOI: 10.1186/s40104-024-01048-x -
Endocrinology Jul 2024Uterine leiomyoma or fibroids are prevalent noncancerous tumors of the uterine muscle layer, yet their origin and development remain poorly understood. We analyzed RNA...
Uterine leiomyoma or fibroids are prevalent noncancerous tumors of the uterine muscle layer, yet their origin and development remain poorly understood. We analyzed RNA expression profiles of 15 epigenetic mediators in uterine fibroids compared to myometrium using publicly available RNA-seq data. To validate our findings, we performed RT-qPCR on a separate cohort of uterine fibroids targeting these modifiers confirming our RNA-seq data. We then examined protein profiles of key N6-methyladenosine (m6A) modifiers in fibroids and their matched myometrium, showing no significant differences in concordance with our RNA expression profiles. To determine RNA modification abundance, mRNA and small RNA from fibroids and matched myometrium were analyzed by UHPLC MS/MS identifying prevalent m6A and 11 other known modifiers. However, no aberrant expression in fibroids was detected. We then mined a previously published dataset and identified differential expression of m6A modifiers that were specific to fibroid genetic sub-type. Our analysis also identified m6A consensus motifs on genes previously identified to be dysregulated in uterine fibroids. Overall, using state-of-the-art mass spectrometry, RNA expression and protein profiles, we characterized and identified differentially expressed m6A modifiers in relation to driver mutations. Despite the use of several different approaches, we identified limited differential expression of RNA modifiers and associated modifications in uterine fibroids. However, considering the highly heterogenous genomic and cellular nature of fibroids, and the possible contribution of single molecule m6A modifications to fibroid pathology, there is a need for greater in-depth characterization of m6A marks and modifiers in a larger and diverse patient cohort.
PubMed: 38946397
DOI: 10.1210/endocr/bqae074 -
The Journal of Maternal-fetal &... Dec 2024The resolution of factors linked to the recurrence of cesarean section defects can be accomplished through a comprehensive technique that effectively addresses the...
BACKGROUND
The resolution of factors linked to the recurrence of cesarean section defects can be accomplished through a comprehensive technique that effectively addresses the dehiscent area, eliminates associated intraluminal fibrosis, and establishes a vascularized anterior wall by creating a sliding myometrial flap.
OBJECTIVE
Propose a comprehensive surgical repair for recurrent and large low hysterotomy defects in women seeking pregnancy or recurrent spotting.
STUDY DESIGN
A retrospective cohort analysis included 54 patients aged 25-41 with recurrent large cesarean scar defects treated at Otamendi, CEMIC, and Valle de Lili hospitals. Comprehensive surgical repair was performed by suprapubic laparotomy, involving a wide opening of the vesicouterine space, removal of the dehiscent cesarean scar and all intrauterine abnormal fibrous tissues, using a glide myometrial flap, and intramyometrial injection of autologous platelet-rich plasma. Qualitative variables were determined, and descriptive statistics were employed to analyze the data in absolute frequencies or percentages. The data obtained were processed using the Infostat statistic program.
RESULTS
Following the repair, all women experienced normal menstrual cycles and demonstrated an adequate lower uterine segment thickness, with no evidence of healing defects. All patients experienced early ambulation and were discharged within 24 h. Uterine hemostasis was achieved at specific points, minimizing the use of electrocautery. The standard duration of the procedure was 60 min (skin-to-skin), and the average bleeding was 80-100 ml. No perioperative complications were recorded. A control T2-weighted MRI was performed six months after surgery. All patients displayed a clean, unobstructed endometrial cavity with a thick anterior wall (Median: 14.98 mm, IQR 13-17). Twelve patients became pregnant again, all delivered by cesarean between 36.1 and 38.0 weeks, with a mean of 37.17 weeks. The thickness of the uterine segment before cesarean ranged between 3 and 7 mm, with a mean of 3.91 mm. No cases of placenta previa, dehiscence, placenta accreta spectrum (PAS), or postpartum hemorrhage were reported.
CONCLUSIONS
The comprehensive repair of recurrent low-large defects offers a holistic solution for addressing recurrent hysterotomy defects. Innovative repair concepts effectively address the wound defect and associated fibrosis, ensuring an appropriate myometrial thickness through a gliding myometrial flap.
Topics: Humans; Female; Adult; Retrospective Studies; Hysterotomy; Pregnancy; Cicatrix; Surgical Flaps; Cesarean Section; Myometrium; Recurrence
PubMed: 38945839
DOI: 10.1080/14767058.2024.2365344 -
Journal of Ovarian Research Jun 2024This study aimed to investigate the mitigating effect of N-acetylcysteine (NAC) on doxorubicin (DOX)-induced ovarian and uterine toxicity in rats using laboratory tests,...
BACKGROUND
This study aimed to investigate the mitigating effect of N-acetylcysteine (NAC) on doxorubicin (DOX)-induced ovarian and uterine toxicity in rats using laboratory tests, ultrasonographic (US) imaging, and histopathology analysis.
METHODS
Forty-eight rats were divided into six groups (n = 8) as follows: Group A (control) (0.5 mL saline administered intraperitoneally [IP]), Group B (a single 10 mg/kg dose of DOX administered IP on day 1), Group C (a single 10 mg/kg dose of DOX administered IP 24 h before sacrifice), Group D (100 mg/kg of NAC administered IP for 21 days), Group E ( a single 10 mg/kg dose of DOX administered IP on day 1 and 100 mg/kg of NAC administered IP for 21 days), and Group F (100 mg/kg of NAC administered IP for 21 days and a single 10 mg/kg dose of DOX administered IP 24 h before sacrifice). The ovaries were examined using B-mode US on days 1, 14, and 21, and the histopathological examinations of the ovaries and the uterus were undertaken after sacrifice on day 22.
RESULTS
Histomorphological analyses showed that ovarian weight decreased after DOX administration in Group B but not in Group E. US revealed a transient increase in ovarian size in Group B and E, reverting to baseline levels over time, as well as a progressive increase in peritoneal fluid in Groups B and E. Group B exhibited a significant decrease in the thickness of the endometrium and myometrium and uterine cornual length, which was not observed in Group E. Histopathological examination showed that DOX caused a decline in follicular count, especially in primordial, secondary, and Graafian follicles, and resulted in follicular atresia, predominantly in Group B. Destructive degeneration/necrosis and vascular changes were most prominently seen in the corpus luteum of Groups C and B. In NAC-treated rats (Groups E and F), although germ cell damage was present, atretic follicles and vascular changes, such as hyperemia and congestion, were reduced. The anti-müllerian hormone (AMH) level was the highest in Group F.
CONCLUSIONS
NAC, an antioxidant, attenuated DOX-induced gonadotoxicity in rats.
Topics: Animals; Female; Doxorubicin; Acetylcysteine; Rats; Ovary; Ultrasonography; Uterus; Antibiotics, Antineoplastic
PubMed: 38943148
DOI: 10.1186/s13048-024-01459-4 -
Differentiation; Research in Biological... Jun 2024A Wt1 conditional deletion, nuclear red fluorescent protein (RFP) reporter allele was generated in the mouse by gene targeting in embryonic stem cells. Upon Cre-mediated...
A Wt1 conditional deletion, nuclear red fluorescent protein (RFP) reporter allele was generated in the mouse by gene targeting in embryonic stem cells. Upon Cre-mediated recombination, a deletion allele is generated that expresses RFP in a Wt1-specific pattern. RFP expression was detected in embryonic and adult tissues known to express Wt1, including the kidney, mesonephros, and testis. In addition, RFP expression and WT1 co-localization was detected in the adult uterine stroma and myometrium, suggesting a role in uterine function. Crosses with Wnt7a-Cre transgenic mice that express Cre in the Müllerian duct epithelium activate Wt1-directed RFP expression in the epithelium of the oviduct but not the stroma and myometrium of the uterus. This new mouse strain should be a useful resource for studies of Wt1 function and marking Wt1-expressing cells.
PubMed: 38941819
DOI: 10.1016/j.diff.2024.100791 -
Chinese Journal of Integrative Medicine Jun 2024To assess the effects of Thunbergia laurifolia L. extract (TLE) on gestational diabetes mellitus (GDM) in a rat model.
OBJECTIVE
To assess the effects of Thunbergia laurifolia L. extract (TLE) on gestational diabetes mellitus (GDM) in a rat model.
METHODS
Thunbergia laurifolin L. leaves were subjected to ethanolic extraction. In vivo study, 50 pregnant rats were randomly divided into 5 groups (10 for each): non-GDM group, GDM induced by streptozotocin (STZ, 60 mg/kg i.p.), metformin (MET) 100 mg/kg, TLE 50, and 500 mg/kg groups. Administration was performed on gestation day 7 until term (day 21). The effects of TLE on blood glucose, insulin levels, lipid profiles, liver enzymes, and maternal performances were assessed. In in vitro study, the effect of TLE was examined using the organ bath for uterine force measurement.
RESULTS
In in vivo study, TLE significantly reduced blood glucose as compared to GDM (P<0.05) with gradually increased insulin level. This effect was consistent with islets of Langerhans restoration. Histologically, the uterine muscular layer displayed a marked increase in fiber area in response to both doses as compared to GDM (P<0.05). Additionally, TLE significantly reduced total cholesterol, triglyceride, and alanine transaminase levels (P<0.05). Intriguingly, TLE also led to a notable augmentation in gravid uterus size, live fetuses count, and implantation numbers, while significantly reducing the post-implantation loss rate associated with fetal classification (P<0.05). Thus, GDM improvements were close to those produced by MET. In in vitro study, TLE exerted a concentration-dependent inhibition of spontaneous uterine contractility (half-maximal inhibition concentration=1.2 mg/L). This inhibitory effect extended to potassium chloride depolarization and oxytocin-mediated contractions. When combined with its major constituent, rosmarinic acid, TLE produced an enhanced inhibitory effect (P<0.05).
CONCLUSIONS
TLE ameliorated blood glucose levels, enhanced uterine muscular structure, and improved maternal and fetal performance in GDM. TLE also displayed tocolytic properties. These findings underscore the need for further exploration of TLE as a potential tocolytic agent to mitigate GDM-associated complications.
PubMed: 38941042
DOI: 10.1007/s11655-024-3764-y -
PloS One 2024Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates...
Prediction of final pathology depending on preoperative myometrial invasion and grade assessment in low-risk endometrial cancer patients: A Korean Gynecologic Oncology Group ancillary study.
OBJECTIVES
Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST.
METHODS/MATERIALS
This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed.
RESULTS
Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4).
CONCLUSIONS
In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.
Topics: Humans; Female; Endometrial Neoplasms; Myometrium; Middle Aged; Adult; Republic of Korea; Neoplasm Invasiveness; Neoplasm Grading; Prospective Studies; Aged; Preoperative Period; Magnetic Resonance Imaging; Carcinoma, Endometrioid
PubMed: 38935680
DOI: 10.1371/journal.pone.0305360 -
International Journal of Molecular... Jun 2024Increased fructose consumption and chronic stress, the major characteristics of modern lifestyle, impact human health; however, the consequences of their combination on...
Increased fructose consumption and chronic stress, the major characteristics of modern lifestyle, impact human health; however, the consequences of their combination on the uterus remain understudied. In this study, we investigated contractile activity, morphology, and intracellular activity of antioxidant enzymes in uteri from virgin Wistar rats subjected to liquid fructose supplementation and/or unpredictable stress over 9 weeks. Contractile activity and uterine response to oxytocin or adrenaline were examined using isolated bath chambers. Fructose supplementation, irrespective of stress, affected uterine morphology by increasing endometrium while decreasing myometrium volume density, attenuated uterine response to increasing doses of oxytocin, and increased glutathione peroxidase activity. Stress, irrespective of fructose, attenuated dose-dependent adrenaline-induced uterine relaxation. Stress, when applied solely, decreased mitochondrial superoxide dismutase activity. In the combined treatment, irregular estrous cycles and both reduced response to oxytocin and to adrenaline (as a consequence of fructose consumption and exposure to stress), along with fructose-related alteration of uterine morphology, were detected. In conclusion, fructose and stress affect uterine contractile activity, irrespective of each other, by inducing completely distinct responses in isolated uteri. In the combined treatment, the effects of both factors were evident, suggesting that the combination exerts more detrimental effects on the uterus than each factor individually.
Topics: Animals; Female; Fructose; Rats; Uterine Contraction; Rats, Wistar; Oxytocin; Uterus; Epinephrine; Stress, Physiological; Stress, Psychological; Superoxide Dismutase; Dietary Supplements; Myometrium; Antioxidants
PubMed: 38928475
DOI: 10.3390/ijms25126770 -
Journal of Robotic Surgery Jun 2024Fibroids are the most common benign tumours of the uterus, often requiring surgery when symptomatic. This study aims to investigate the impact of surgery using two... (Comparative Study)
Comparative Study
Fibroids are the most common benign tumours of the uterus, often requiring surgery when symptomatic. This study aims to investigate the impact of surgery using two methods, laparoscopy and laparotomy, on the thickness and vascularity of the uterine myometrium at the site of myomectomy scar (comparing sonographic features at the surgical scar site, including thickness, vascularity, and the extent of fibrotic tissue, in both open and laparoscopic surgical approaches). In this clinical trial, 100 women with type 2-5 fibroids and clinical symptoms, seeking surgery et al. Zahra Hospital, were enrolled in two groups: laparoscopy and laparotomy. Inclusion criteria were a maximum fibroid size of 8 cm and, in the case of multiple fibroids, a maximum of three, with the largest being 8 cm. 6 months post-surgery, sonographic assessments of the myomectomy scar site were compared between both groups. Participants showed no significant differences in demographic and obstetric factors. The most common clinical symptom (87%) in both groups was abnormal uterine bleeding (AUB). The mean hospital stay duration was statistically significantly lower in the laparoscopy group at 1.64 (SD 0.56) compared to 1.89 (SD 0.58) in the laparotomy group (p = 0.028). Additionally, the decrease in haemoglobin levels was 0.89 (SD 0.92) and 1.87 (SD 2.24) units, respectively, which showed a statistically significant difference (p = 0.003). The duration of surgery was significantly shorter in the laparotomy group (p = 0.001). Abdominal pressure was not observed in the laparoscopy group, while 12% of the laparotomy group reported complaints (p = 0.013). Based on the results obtained in this study, it can be concluded that there was no difference between these two methods in terms of improving uterine thickness and associated complications. However, the decrease in haemoglobin levels and the length of hospital stay were lower in patients undergoing laparoscopy.
Topics: Humans; Female; Laparoscopy; Uterine Myomectomy; Cicatrix; Adult; Myometrium; Laparotomy; Leiomyoma; Uterine Neoplasms; Ultrasonography; Length of Stay; Middle Aged
PubMed: 38926240
DOI: 10.1007/s11701-024-01983-x -
F&S Science Jun 2024To study the differences in immune cell profile in uterine fibroids (Fib) and matched myometrium (Myo).
OBJECTIVE
To study the differences in immune cell profile in uterine fibroids (Fib) and matched myometrium (Myo).
DESIGN
Observational Study SETTING: Laboratory Study PATIENTS: The study included tissue that was collected from ten pairs of fibroid and matched myometrium from women, not on hormonal medications, undergoing hysterectomy and myomectomy.
INTERVENTIONS
None MAIN OUTCOME MEASURES: Differences in immune cell and cytokine composition between fibroid and matched myometrium RESULT(S): The mass cytometry analysis indicated that fibroids had a significantly higher number of NK cells, total macrophages, M2 macrophages, and conventional dendritic cells when compared to matched myometrium from the same patient. In contrast, fibroids had significantly fewer CD3 and CD4 T cells when compared to myometrium. The mass cytometry analysis did not show any significant difference in the number of resting mast cells. IFC and IHC imaging confirmed the CytoF results, showing a significantly higher (p<0.05) number of NK, tryptase-positive mast cells indicative of mast cell activation, total macrophage, and M2 cells in Fibroids and a significantly lower (p<0.05) number of CD3 and CD4 T cells. The cytokine assay revealed significantly increased (p<0.05) levels of IFNA2, Il-1α, and PDGF-AA and significantly lower levels of M-CSF and IL-1RA in Fib.
CONCLUSION
Our results show significant differences in immune cell populations and cytokine levels between Fib and Myo. There was a significant increase in total number of macrophages, M2 macrophages, NK cells, and dendritic cells and a significant decrease in CD3 and CD4 T cells in Fib. IHC confirmed no differences in total resting mast cell count, but a significant increase in tryptase-positive mast cells in Fib. Fibs also expressed significantly higher levels of IFNA2, IL-1α, and PDGF-AA and significantly lower levels of IL-1RA and M-CSF as compared with matched myometrium. These findings provide a foundation for further studies exploring the role of immune cells in Fib development.
PubMed: 38925276
DOI: 10.1016/j.xfss.2024.06.004