Bovine lactoferrin suppresses inflammatory cytokine expression in endometrial stromal cells in chronic endometritis.

Chronic endometritis (CE) is a type of chronic inflammation in the endometrium that is associated with infertility, which is primarily due to implantation failure. Antibiotics are the most common treatment for CE. However, some patients with CE are resistant to antibiotic treatment, while others refuse this treatment. Therefore, we focused on lactoferrin (Lf), which exhibits antimicrobial and anti-inflammatory properties, and studied its effect on inflammation in endometrial stromal cells (ESCs) from patients with CE. Endometrial tissue was collected from patients with CE, and ESCs were isolated and cultured. When ESCs were cultured with bovine lactoferrin (bLf: 1 mg/mL), the mRNA expression of TNF-α (p < 0.05) and IL-1ß (p < 0.01) was significantly decreased compared with that in cells cultured without bLf. The level of TNF-α protein in the culture medium was significantly decreased (p < 0.01), while that of IL-1ß was also decreased, but not significantly (p < 0.10), when 1 mg/mL of bLf was added to the culture medium. When more inflammation was induced artificially by adding 0.1 ng/mL of TNF-αto ESCs, the addition of bLf (1 mg/mL) to ESCs decreased IL-6 and IL-1ß mRNA expression to levels similar to those in ESCs without TNF-α treatment. Furthermore, it was revealed that the actions of bLf are mediated by the AKT and MAPK intracellular signaling pathways, which are mechanisms by which the increase in TNF-α-induced cytokine expression is suppressed in ESCs. bLf suppresses the expression of inflammatory cytokines in human ESCs and may be a new therapeutic candidate for CE.

Impact of an oral gonadotropin-releasing hormone antagonist on severe ovarian hyperstimulation syndrome in a patient with breast cancer who received a sustained-release gonadotropin-releasing hormone agonist: A case report.

Postoperative hormone therapy for hormone-sensitive patients with breast cancer is important to prevent a recurrence. As hormone therapy does not induce infertility in patients, fertility-preserving therapy is not provided during treatment. Here, however, we performed controlled ovarian stimulation and embryo freezing for fertility preservation under the influence of a sustained-release gonadotropin-releasing hormone agonist in a patient with breast cancer whose postoperative treatment plan was changed from hormone therapy to chemotherapy. After oocyte retrieval, the patient developed treatment-resistant severe symptomatic ovarian hyperstimulation syndrome. Following treatment with oral gonadotropin-releasing hormone antagonist, her symptoms immediately improved, and she could receive chemotherapy on schedule.

Induction of the epithelial-mesenchymal transition in the endometrium by chronic endometritis in infertile patients.

BACKGROUND: The purpose of the present study was to evaluate the relationship between chronic endometritis and the epithelial-mesenchymal transition in the endometrium of infertile patients in the implantation phase. METHODS: Endometrial biopsy specimens from 66 infertility patients were analyzed. The presence of chronic endometritis was investigated by immunostaining for CD138. Immunohistochemical staining for E-cadherin, N-cadherin, Slug, and Snail was performed, and the expression profiles were statistically analyzed according to the presence of chronic endometritis. When the loss of E-cadherin expression and/or the positive expression of N-cadherin was detected, the specimen was considered epithelial-mesenchymal transition-positive. Epithelial-mesenchymal transition-positive cases were also statistically analyzed according to the presence of chronic endometritis. The characteristics of the patients in the epithelial-mesenchymal transition-positive and epithelial-mesenchymal transition-negative groups were compared. The association between variables, including age, body mass index, gravidity, parity, and each causative factor of infertility and epithelial-mesenchymal transition positivity was analyzed. RESULTS: The rates of the loss of E-cadherin expression, the gain of N-cadherin and epithelial-mesenchymal transition positivity were significantly higher in chronic endometritis patients. The expression of Slug, cytoplasmic Snail, and nuclear Snail was also detected at significantly higher rates in chronic endometritis patients. Chronic endometritis were related to the epithelial-mesenchymal transition. CONCLUSION: The epithelial-mesenchymal transition was frequently detected in the endometrium in infertile patients with chronic endometritis. Since the epithelial-mesenchymal transition is associated with chronic endometritis, the epithelial-mesenchymal transition appears to be involved in the alteration of mechanisms of implantation.

Alteration in endometrial helper T-cell subgroups in chronic endometritis.

PROBLEM: The effect of chronic endometritis (CE) on the subpopulation of CD4+ T cells, Th1, Th2, Th17, and regulatory T cells in the endometrium is unknown. METHOD OF STUDY: Lymphocytes were isolated from the endometrium of CE patients (n = 12) and non-CE patients (n = 7). The CD4+ T-cell profile was analyzed by flow cytometry and immunofluorescence. RESULTS: In the endometrium of CE patients, there were significantly more Th1 cells among CD4+ cells and fewer Th2 cells in comparison to non-CE patients. No marked difference was observed in Th17 cells or Foxp3+ Treg cells. Moreover, the proportion of Th1 cells increased and the proportion of Th2 cells decreased as the number of CD138+ cells increased. Furthermore, when the localization of CD138+ cells and CD4+ cells was examined, CD4+ cells were found to be clustered around CD138+ cells in CE patients. CONCLUSION: The CD4+ T-cell profile in the endometrium is altered in women with CE. This finding may help to clarify the pathophysiology and development of treatment methods for CE.

Ovarian cryopreservation for children aged 3 years or younger: A report of three cases.

Ovarian tissue cryopreservation has recently been performed as an option for fertility preservation in prepubertal girls with cancer. In this study, ovarian tissue was cryopreserved from 3 girls of 3 years of age or younger during a 3-year period at our institution. Case 1 was a 1-year-old girl, who was diagnosed with a yolk sac tumor in the sacral region. Case 2 was a 2-year-old girl, who was diagnosed with retroperitoneal neuroblastoma. Case 3 was a 3-year-old girl, who was diagnosed with cerebellar medulloblastoma. All patients had planned to undergo chemotherapy that would affect the ovarian reserve. Because these patients were toddlers, consideration of ethics, the surgical procedure and postoperative management, and optimal method for freezing ovarian tissue was necessary, although gynecologists rarely experience these challenges in daily clinical practice. We herein present the clinical course of these three cases and discuss the peculiarities and countermeasures of ovarian cryopreservation in children.

Relationship of chronic endometritis with chronic deciduitis in cases of miscarriage.

BACKGROUND: The presence of chronic deciduitis (CD) was determined in patients diagnosed with or without chronic endometritis (CE) before pregnancy. OBJECTIVE: To study the effect of CE on decidua in cases of miscarriage. METHODS: Decidual tissue was obtained from the patients who miscarried at the first pregnancy within a year after the diagnosis of the presence or absence of CE. The number and distribution pattern of plasma cells stained with CD138 in decidual tissue in 10 high-power fields (HPFs) was examined. The prevalence of CD diagnosed with four different grade; grade 0, no plasma cell in 10 HPFs, thus Non-CD;grade 1, rare single plasma cells; grade 2, rare clusters or more than 5 single cells total; and grade 3, many plasma cells with more than 5 clusters, were examined and compared between Non-CE and CE. RESULTS: The incidence rate of CD of grade2 + 3 was significantly higher in CE than Non-CE (53.8%; 7/13 vs. 0%; 0/13, P < 0.01). Presence of clusters or a number of plasma cells in 10 HPFs of decidua showed a sensitivity of 53.8%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 68.4% for the diagnosis of CE. CONCLUSION: Presence of clusters of plasma cells or five or more of plasma cells in decidua was found in more than half of CE, but not found in Non-CE. When CD with cluster or five or more of plasma cells is confirmed histologically in miscarriage decidual tissue, the presence of CE before the pregnancy should be suspected.

Endometrial Immunity for Embryo Implantation and Pregnancy Establishment.

The uterus is an organ for raising the fetus, and its lumen is lined by the endometrium. The endometrium is an important site for the implantation and maturation of fertilized eggs. The endometrium undergoes repetitive proliferation, maturation (decidualization), and exfoliation changes every menstrual cycle. At the same time, the number and type of endometrial immunocompetent cells vary during the menstrual cycle. At the implantation stage, the immunocompetent cells occupy approximately half of the endometrial cells. Immunocompetent cells normally eliminate pathogenic microorganisms to protect the body; however, they also promote immune tolerance to accept the fetus during pregnancy. The immunocompetent cells in the uterus can perform both these functions. With the establishment of pregnancy, stimuli from the trophoblast (placenta) and fetus can also change the immune environment of the uterus, and pregnancy can be maintained only when the immune system is well adapted to the stimuli of some hormones and the fetus. Immunity for the establishment of pregnancy is not simple because multiple immunocompetent cells are involved in establishing and maintaining pregnancy. To understand the immune mechanisms associated with the establishment of pregnancy, we have to learn about each immune cell. This review, therefore, discusses the roles and distribution of the immunocompetent cells inside the uterus during menstruation and early pregnancy.

Dienogest suppresses the activation of primordial follicles and preserves the primordial follicle stockpile for fertility in mice.

The aim of the present study was to characterize the effect of long-term usage of dienogest, a fourth-generation progestin that possesses progestogen and anti-androgen activities, on the stockpile of oocytes and fertility after administration. Female ICR mice (100 days old) were divided into a dienogest group and a control group. The mice received 16 consecutive subcutaneous injections of 5 mg dienogest dissolved in corn oil or corn oil as a vehicle control every 4 days. The mice treated with dienogest had more total offspring and larger litter sizes after the final administration than the mice treated with the vehicle control. Greater numbers of primordial follicles were detected at both 4 and 80 days after the final administration. No significant differences were found in serum anti-Müllerian hormone concentrations at 4 and 80 days after the final dienogest administration. The ratio of primary to primordial follicles was decreased in 3-day-old newborn ovaries cultured for 4 days with dienogest (10-7, 10-6 and 10-5 mol/l) compared with ovaries cultured without dienogest. The results of the present study indicate that dienogest suppresses the activation of primordial follicles during its administration and preserves the primordial follicle stockpile and subsequent fertility in mice.