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Embryo implantation is crucial for ensuring a successful pregnancy outcome and subsequent child health. The intrauterine environment during the peri-implantation period shows drastic changes in gene expression and cellular metabolism in response to hormonal stimuli and reciprocal communication with embryos. Here, we performed spatial transcriptomic analysis to elucidate the mechanisms underlying embryo implantation. Transcriptome data revealed that lipid metabolism pathways, especially arachidonic acid-related (AA-related) ones, were enriched in the embryo-receptive luminal epithelia. Cyclooxygenases (COXs), rate-limiting enzymes involved in prostaglandin production by AA, were spatiotemporally regulated in the vicinity of embryos during implantation, but the role of each COX isozyme in the uterus for successful pregnancy was unclear. We established uterine-specific COX2-knockout (uKO) and COX1/uterine COX2-double-KO (COX1/COX2-DKO) mice. COX2 uKO caused deferred implantation with failed trophoblast invasion, resulting in subfertility with reduced pregnancy rates and litter sizes. COX1/COX2 DKO induced complete infertility, owing to abrogated embryo attachment. These results demonstrate that both isozymes have distinct roles during embryo implantation. Spatial transcriptome and lipidome analyses revealed unique profiles of prostaglandin synthesis by each COX isozyme and spatiotemporal expression patterns of downstream receptors throughout the endometrium. Our findings reveal previously unappreciated roles of COXs at the fetomaternal interface to establish early pregnancy.

Objectives: The objective of the study was to evaluate the feasibility and quality of anesthesia-free in-office hysteroscopic morcellation for the treatment of endometrial polyps., Materials and Methods: A prospective, single-center, open-label, single-arm clinical trial was conducted to evaluate the efficacy of hysteroscopic morcellation for endometrial polyps or retained products of conception. All surgical procedures were performed using the TruClear™ 5C system in the office setting without anesthesia. The primary endpoint was the success rate of surgery, defined as the completion of the operation. The secondary endpoints were operating time, fluid deficit, adverse events, pain evaluated by Visual Analog Scale (VAS) scores, and recurrence rate., Results: Ninety-five patients underwent hysteroscopic morcellation without anesthesia and received the treatment. The success rate of surgery was 100% (95/95), and the mean operating time was 7.3 min. Adverse events occurred in only 2.1% (2/95), with vasovagal reflex. The mean VAS scores during the procedure ranged from 2.4 to 3.1, and the recurrence rate after 6 months was 2.1% (1/47), with a pregnancy rate of 33% (11/33). When comparing nulliparous and parous patients, the success rate and the operating time were equivalent, and the mean VAS scores during the procedure were both within tolerable levels but significantly higher in nulliparous patients (3.3-4.5 vs. 1.6-1.9, P < 0.001)., Conclusion: This study demonstrated that anesthesia-free in-office hysteroscopic morcellation for endometrial polyps can be safely performed with feasible quality and only tolerable pain. This less-invasive procedure is expected to become more widespread in future., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Gynecology and Minimally Invasive Therapy.)

Background: Adenomyosis is a common gynecological disease in women of reproductive age and causes various symptoms such as dysmenorrhea and heavy menstrual bleeding. However, the influence of pregnancy on the progression of adenomyosis remains unclear. The insight into whether the size of adenomyosis is increased, decreased, or unchanged during pregnancy is also undetermined. The current study aimed to evaluate the influence of pregnancy in patients with symptomatic adenomyosis., Methods: This study retrospectively enrolled patients diagnosed with adenomyosis by magnetic resonance imaging between 2015 and 2022 at The University of Tokyo Hospital. Uterine size changes were evaluated by two imaging examinations. In the pregnancy group, the patients did not receive any hormonal and surgical treatments, except cesarean section, but experienced pregnancy and delivery between the first and second imaging examinations. In the control group (nonpregnancy group), the patients experienced neither hormonal and surgical treatments nor pregnancy from at least 1 year before the first imaging to the second imaging. The enlargement rate of the uterine size per year (percentage) was calculated by the uterine volume changes (cm 3 ) divided by the interval (years) between two imaging examinations. The enlargement rate of the uterine size per year was compared between the pregnancy group and the control group., Results: Thirteen and 11 patients with symptomatic adenomyosis were included in the pregnancy group and in the control group, respectively. The pregnancy group had a lower enlargement rate per year than the control group (mean ± SE: -7.4% ± 3.6% vs. 48.0% ± 18.5%, P < 0.001), indicating that the size of the uterus with adenomyosis did not change in the pregnancy group., Conclusions: Pregnancy is associated with reduced progression of symptomatic adenomyosis., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: With the increased use of total laparoscopic hysterectomy (TLH), the use of robotic-assisted laparoscopic hysterectomy (RALH) has increased due to its technical advantages. On the other hand, RALH has some disadvantages, including its high cost, which includes not only the purchase price of robotic technology systems but also the running cost and long preparation time for setting assistant robots. Therefore, an overall understanding of the characteristics of RALH is needed., Study Design: We reviewed the medical records of 432 patients with TLH and 93 patients with RALH from January 1, 2015, to December 31, 2022. In this analysis, we excluded certain cases with concomitant laparoscopic cystectomy (LC) and a heavy uterus (> 400 g). First, the patient characteristics of the TLH and RALH groups, including operation time and blood loss amount, were compared. Then, among these cases, we sought to predict difficult cases for TLH and RALH by identifying risk factors related to each of the following three categories of operational complications: "long operation time", "massive blood loss" and "other complications". For this purpose, multivariate logistic regression analyses were performed to assess the influence of each of 7 representative factors, namely, "advanced age", "high body mass index (BMI)", "nulliparity", "concomitant pelvic lymphadenectomy (PLA)", "heavy uterus", "abdominal adhesion", and "large leiomyoma"., Results: In the simple comparison without various factors, there was an advantage of RALH in both the average operation time and blood loss amount. However, in the multivariate logistic regression analyses, a significant risk was detected in the following relationships: 1) between "long-term operation" and "abdominal adhesion" and 2) between "other complications" and "heavy uterus"., Conclusions: RALH has sufficient advantages over TLH regarding at least in terms of blood loss amount; however, since RALH may have potential weaknesses in the context of complex cases, additional cases and analyses are needed., Competing Interests: None., (©2023PublishedbyElsevierB.V.)

Under ovarian hormone control, dormant blastocysts obtain implantation capacity (known as blastocyst activation) through their global gene expression. After the activated blastocysts communicate with the receptive uterus, the implantation-competent blastocysts start the implantation. Although dormant and activated blastocysts have different gene expression levels, the regulatory mechanisms underlying these transcriptions remain unclear. Hence, this study aimed to analyze epigenetic marks in dormant and activated blastocysts. In mice, blastocyst dormancy is artificially induced by daily progesterone injection without estrogen supplementation after peri-implantation ovariectomy; when estrogen is administered concomitantly, blastocyst activation and implantation occur. These phenomena demonstrate a mouse model of delayed implantation. We collected dormant and activated blastocysts from a delayed implantation mouse model. RNA-seq, methylated DNA immunoprecipitation (MeDIP)-seq, and chromatin immunoprecipitation (ChIP)-seq for H3K4 me3 and H3K27 me3 were performed using dormant and activated blastocysts. Cell cycle-related transcripts were affected during blastocyst activation. DNA methylations were accumulated in downregulated genes in the activated blastocysts. Histone H3 trimethylations were globally altered between the dormant and activated blastocysts. Dormant and activated blastocysts have unique methylation patterns on DNA and histone H3, with high correlation to gene expression. DNA methylation and histone modification can regulate preimplantation blastocyst activation., (© 2022. Society for Reproductive Investigation.)

Objective: To reduce intraoperative blood loss in laparoscopic myomectomy, uterine artery occlusion or temporary uterine artery clipping have been employed. Recently, in addition to these techniques, temporary uterine artery ligation has been reported as a new method that has less invasive effects on fertility and needs no special devices to be used. This study aimed to evaluate the effect of temporary uterine artery ligation to minimize intraoperative blood loss during laparoscopic myomectomy., Study Design: This was a retrospective case-control study at the department of Obstetrics and Gynaecology, University Hospital Mizonokuchi, Teikyo University School of Medicine. A total of 264 patients with uterine leiomyoma who underwent laparoscopic myomectomy were enrolled in this study. We divided the patients into two groups, those who underwent temporary uterine artery ligation (52 patients) and those who did not (212 patients) and compared the operation time, blood loss volume, and other indexes. Second, to identify influential factors, we assessed the effects of 11 representative factors on massive blood loss or a prolonged operation time using multivariate analysis., Results: The intraoperative blood loss volume was decreased by approximately half with the addition of temporary uterine artery ligation (75.1 ± 73.6 ml vs. 158.5 ± 233.2 ml, p = 0.011), but the operation time was longer (200.5 ± 46.9 min vs. 160.1 ± 51.3 min, p < 0.001). Among the 264 patients, 25 patients (9/52 in the case group and 16/212 in the control group) had a prolonged operation time (≥ 240 min), and 24 patients (1/52 in the case group and 23/212 in the control group) experienced massive blood loss (≥ 400 ml). In the multivariate analysis, high body mass index, concomitant surgery and temporary uterine artery ligation showed a positive association with a prolonged operative time, and the presence of single leiomyoma showed a negative association. Concomitant surgery and the presence of large leiomyoma showed a positive association with massive blood loss, and temporary uterine artery ligation showed a negative association., Conclusions: By performing temporary uterine artery ligation during laparoscopic myomectomy, the volume of intraoperative blood loss could be decreased, especially in patients with large leiomyomas. However, because this procedure prolongs the operation time, there is still room for improvement., (© 2022 The Authors.)

Background: Fluoxetine is one of the most widely prescribed antidepressants and a selective inhibitor of presynaptic 5-HT transporters. The fornix is the commissural and projection fiber that transmits signals from the hippocampus to other parts of the brain and opposite site of hippocampus. The corpus callosum (CC) is the largest of the commissural fibers that link the cerebral cortex of the left and right cerebral hemispheres. These brain regions play pivotal roles in cognitive functions, and functional abnormalities in these regions have been implicated in the development of various brain diseases. The purpose of the present study was to investigate the effects of fluoxetine on the proliferation and/or survival of microglia and oligodendrocyte progenitor cells (OPCs) in the fornix and CC, the white matter connecting cortical-limbic system, of the adult mouse brain., Methods: The effects of fluoxetine on the proliferation and/or survival of microglia and OPCs were examined in lipopolysaccharide (LPS)-treated and normal mice. Proliferating cells were detected in mice that drank water containing the thymidine analog, bromodeoxyuridine (BrdU), using immunohistochemistry., Result: Fluoxetine significantly attenuated LPS-induced increases in the number of BrdU-labeled microglia and morphological activation from the ramified to ameboid shape, and decreased the number of BrdU-labeled OPCs under basal conditions., Conclusions: The present results indicate that fluoxetine exerts inhibitory effects on LPS-induced increases in the proliferation and/or survival and morphological activation of microglia and basal proliferation and/or survival of OPCs in the fornix and CC of adult mice.

The myelin sheath is critical in maintaining normal functions of the adult central nervous system (CNS) and the loss of the myelin sheath results in various neurological diseases. Although remyelination is the intrinsic repair system against demyelination that new myelin sheath is formed around axons in the adult CNS, little has been reported on remyelination system in the medulla oblongata. In the present study, we showed that the proliferation of oligodendrocyte progenitor cells (OPCs) was increased in the medulla oblongata by lysophosphatidylcholine (LPC)-induced focal demyelination, but that of NSCs was not changed. The inhibition of vascular endothelial growth factor (VEGF)- and platelet-derived growth factor (PDGF)-signaling suppressed the proliferation of OPCs by LPC-induced demyelination. Thus, the present study indicates that resident OPCs contribute to focal remyelination and VEGF and PDGF signaling is required for the proliferation of OPCs in the medulla oblongata of the adult mouse., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Experimental autoimmune encephalomyelitis (EAE) is primarily used as an animal model of autoimmune demyelinating disease, multiple sclerosis. In this study, we found the proliferative rate of oligodendrocyte progenitor cells (OPCs) in the medulla elevated twofold above control levels during EAE and new generation of mature oligodendrocytes was increased as well. Although astrocytes showed hypertrophic reactive phenotype, a new generation of them was rare. Astrocyte- and tanycyte-like neural stem cells (NSCs), multipotent NSCs, did not augment their low proliferative rate. Thus, the present study demonstrates that resident OPCs derived from NSCs contribute to remyelination in the medulla oblongata in EAE mice., (Copyright © 2018 Elsevier B.V. All rights reserved.)