Background: Dysmature cumulus cells are lower fertilization rates and abnormalities in embryonic development compared to maturation cumulus cells. Morphological evaluation of cumulus–oocyte complexes (COCs) considered the possibility that differences may also be found in gene expression. Purpose: To identify hallmarks for evaluating oocyte quality by investigating gene expression patterns in human cumulus cells surrounding oocytes. Methods: Cumulus cells were obtained from the cumulus–oocyte complex of infertile women treated with assisted reproductive technology. Based on maturity level, the cumulus cells were classified into two categories, i.e., dysmature cumulus cell (DCC) and maturation cumulus cell. DCCs were subjected to gene expression analysis using next-generation sequencing and compared with COCs that are in the process of maturation as controls. Results: The expression levels of genes involved in the Wnt signal/β-catenin pathway were significantly reduced in DCCs compared with those in control cells. Moreover, the expression levels of genes involved in multiple pathways associated with apoptosis were also significantly reduced compared with those in control cells. Conclusions: DCCs showed significant decreases in apoptosis- and Wnt/β-catenin signaling-associated gene expression. DCCs could be classified by morphological evaluation, and the method described in this study may be useful as an oocyte quality estimation tool.
Purpose Following reports of an increase in implantation and pregnancy continuation rates by a higher percentage of Lactobacillus in the intrauterine microbiota, it has received attention in infertility treatment. This study aimed to examine Japanese women for intrauterine microbiota. Methods The clinical background factors in women that influence the abundance of Lactobacillus in the bacterial microbiota were examined. We included 147 patients (31 and 116 in the follicular and luteal phase, respectively), from June 2018 to June 2020, who underwent their first intrauterine microbiota test and had not used antibiotics for at least 4 weeks before the test. In the luteal phase, we compared the background factors of women in cases with 90% or more and less than 90% of Lactobacillus. Differences in the intrauterine microbiota were examined during the follicular and luteal phases. Results The proportion of Lactobacillus tended to be low among women aged 36 years and older with a history of childbirth (P = 0.0631). Some bacteria were only detected during the follicular and luteal phases, and the bacterial microbiota may change during the menstrual cycle. Conclusion Bacterial microbiota in the uterus may differ between the follicular and luteal phases. Furthermore, it was shown that the rate of Lactobacillus may be lower in women (older than 36 years) who had given birth, indicating that intrauterine microbiological testing may be considered for these women in clinical practice. Lay summary Good implantation and pregnancy continuation rates have been reported when the proportion of the bacteria Lactobacillus is high in the uterus (intrauterine) bacterial population (microbiota). In this study, we assessed whether the clinical background of Japanese women (age, history of pregnancy and childbirth, and presence of gynecological or hormonal disorders) affect the proportion of intrauterine microbiota. Intrauterine samples were collected and sequenced to evaluate the intrauterine microbiota and the composition ratio of each bacterium. Comparing the percentage of Lactobacillus in the latter phase of the menstrual cycle with the clinical background, it was found that the percentage tended to be lower in women with a history of childbirth. We compared the intrauterine microbiota between the first phase and latter phase of the menstrual cycle and revealed that it may differ between the two phases. Advances in the development of criteria for assessing intrauterine microbiota are expected.
Advances in prenatal molecular testing have made it possible to diagnose most genetic disorders early in gestation. In utero mesenchymal stem cell (MSC) therapy can be a powerful tool to cure the incurable. With this in mind, this method could ameliorate potential physical and functional damage. However, the presence of maternal T cells trafficking in the fetus during pregnancy is thought to be the major barrier to achieving the engraftment into the fetus. We investigated the possibility of using maternal adipose-derived stem cells (ADSCs) for in utero transplantation to improve engraftment, thus lowering the risk of graft rejection. Herein, fetal brain engraftment using congenic and maternal ADSC grafts was examined via in utero stem cell transplantation in a mouse model. ADSCs were purified using the mesenchymal stem cell markers, PDGFRα, and Sca-1 via fluorescence-activated cell sorting. The PDGFRα þ Sca-1 þ ADSCs were transplanted into the fetal intracerebroventricular (ICV) at E14.5. The transplanted grafts grew for at least 28 days after in utero transplantation with PDGFRα þ Sca-1 þ ADSC, and mature neuronal markers were also detected in the grafts. Furthermore, using the maternal sorted ADSCs suppressed the innate immune response, preventing the infiltration of CD8 T cells into the graft. Thus, in utero transplantation into the fetal ICV with the maternal PDGFRα þ Sca-1 þ ADSCs may be beneficial for the treatment of congenital neurological diseases because of the ability to reduce the responses after in utero stem cell transplantation and differentiate into neuronal lineages.
Fertility preservation is an important concern for young cancer patients. Oocyte or embryo cryopreservation prior to chemotherapy administration is desirable but often difficult for patients with hematopoietic and lymphoid tissue tumors. In this study, we examined the results of fertility preservation therapy in patients with hematopoietic and lymphoid tissue tumors. We retrospectively examined hematopoietic and lymphoid tissue tumors of five patients who underwent oocyte cryopreservation as a fertility preservation therapy after chemotherapy, at Showa University Hospital from February 2017 to September 2020. Eleven treatment cycles were administered (one of which was cancelled). The mean age of the patients was 28.6 years. The mean controlled ovarian stimulation duration for 10 cycles was 15.9 days, the mean total gonadotropin dose was 3705 IU, and the mean peak E2 was 502.8 (pg/mL). The mean number of eggs retrieved was 3.2, the mean number of mature oocytes was 2.1, and the mean maturation rate (mature oocytes/returned oocytes) was 70.7%. Fertility preservation procedures in the early period after chemotherapy may be viable because they allow for the acquisition of mature oocytes, even though the procedures may take longer and yield fewer oocytes.
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