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Progesterone (P4) and glucocorticoid (GC) play crucial roles in the immunoregulation of a mother to accept and maintain a semi-allogenic fetus. P4 concentration increases during pregnancy and becomes much higher in the placenta than in the other peripheral tissues, wherein the concentration of cortisol (COR), the most abundant GC and a strong immunosuppressor, remains uniform throughout the rest of the body. Here, we evaluated the effect of a high-P4 environment on pregnant immunity by comparing it with COR. Naïve T cell proportion increased transiently in peripheral blood of pregnant women just after delivery and decreased after one month. T cells stimulated with superantigen toxic-shock-syndrome-1 (TSST-1) in the presence of P4 stayed in the naïve state and did not increase, irrespective of the presence of COR, and reactive T cells could not survive. Treatment of T cells with P4 without T cell receptor (TCR) stimulation transiently suppressed T cell activation and proliferation, whereas the levels remain unaltered if P4 was not given before stimulation. Comparison of the engraftment and response against specific antigens using hu-PBL-NOG-hIL-4-Tg mice showed that P4-pretreated lymphocytes preserved CD62L expression and engrafted effectively in the spleen. Moreover, they produced antigen-specific antibodies, whereas COR-pretreated lymphocytes did not. These results suggest that a high-P4 environment suppresses T cell activation and induces T cell migration into lymphoid tissues, where they maintain the ability to produce anti-pathogen antibodies, whereas COR does not preserve T cell function. The mechanism may be pivotal in maintaining non-fetus-specific T cell function in pregnancy.

The status of humoral immunity of cancer patients is not clear compared to cellular immunity because the ability of specific antibody production is difficult to analyze in vitro. We previously developed a humanized mouse model to evaluate antigen-specific antibody production by transplanting human peripheral blood mononuclear cells (PBMCs) into NOG-hIL-4-Tg mice (hu-PBL hIL-4 NOG). In this study, these mice were transplanted with PBMCs derived from breast cancer patients (BC) and immunized with a human epidermal growth factor receptor 2 (HER2) peptide, CH401MAP, to analyze humoral immunity of BCs. The hu-PBL hIL-4 NOG mice recapitulated immune environment of BCs as the ratio of CD8+/CD4 + T cells was lower and that of PD-1 + T cells were higher compared to healthy donor (HD). Diverse clusters were detected in BC-mouse (BC-M) plasma components involving immunoglobulins and complements unlike HD-M, and there was a significant diversity in CH401MAP-specific IgG titers in BC-M. The number of B cell clones producing high CH401MAP-specific IgG was not increased by immunization in BC-M unlike HD-M. These results demonstrated that the humoral immunity of BCs appeared as diverse phenotypes different from HDs in hu-PBL hIL-4 NOG mice, which may provide important information for the study of personalized medicine. (198)

T cell stimulation by bacterial superantigens induces a cytokine storm. After T cell activation and inflammatory cytokine secretion, regulatory T cells (Treg) are produced to suppress the immune response. Coccomyxa sp.KJ (IPOD FERM BP-22254), a green alga, is reported to regulate immune reactions. Therefore, we examined the effects of Coccomyxa sp.KJ extract (CE) on the superantigen-induced immune response. When human peripheral blood mononuclear cells (PBMCs) were stimulated with toxic shock syndrome-1 (TSST-1) in the presence of CE, the number of activated T cells decreased moderately. Purified T cells stimulated in the presence of CE comprised more non-proliferating cells than those stimulated in the absence of CE, whereas some T cells proliferated more quickly. The levels of activation markers on the stimulated T cells increased in the presence of CE. Most of the inflammatory cytokines did not change but IL-1β, IL-17, IL-4, and IL-13 secretion increased, whereas that of IL-2, TNF-α, and IL-18 decreased. IL-10 secretion was also decreased by CE treatment, suggesting that the immune response was not suppressed by Treg cells. CE enhanced the expression of stem cell-like memory cell markers in T cells. These results suggest that CE can regulate the fate of T cells and can help to ameliorate superantigen-induced T cell hyperactivation and immune suppression.

While pregnancy-related proteins (PRP) are known to contribute to immunotolerance during pregnancy, their significance to development of invasive placenta is unclear. We compared PRP expression in humans and the common marmoset (Callithrix jacchus), a new-world monkey. Invasive placenta was observed at the maternal-foetal interface of marmoset placenta from green fluorescent protein (GFP)-expressing foetus and wild type mother. The pregnancy zone protein (PZP) and alpha-2 macroglobulin-like 1 (A2ML1) proteins exhibited the most prominent increase in expression during the second trimester in humans and marmoset, respectively. In humans, PZP accumulated at the maternal-foetal interface and A2ML1 accumulated in the amnion. Similarly, A2ML1 mRNA was detected in marmoset placenta. These proteins belong to the A2M family of protease inhibitors, and both PZP and A2ML1 share around 90% homology between human and marmoset and have highly conserved structures. However, the protease-reacting bait regions of the proteins had lower homology (56.8–60.7% in proteins) relative to the rest of the sequence. Notably, the cleavage site of a proinflammatory proline-endopeptidase was preserved in human PZP and marmoset A2ML1. These proteins contain multiple sites that are cleaved by proteases involving proline-endopeptidase. Systemic regulation of these A2M family proteins may be important in animals with invasive placenta.

Tubal reanastomosis or tubal reversal, a surgical method used to reverse tubal sterilization, may be an option for women who for various reasons wish to reestablish their fertility. A 38-year-old Chinese woman, gravida 2, para 2 (both delivered through cesarean section) presented to our outpatient gynecology clinic requesting bilateral tubal recanalization. After other causes of infertility were excluded, laparoscopic tubal reanastomosis was performed. Here, we present our tips and techniques for laparoscopic tubal reanastomosis that rapidly resulted in an intrauterine pregnancy, which delivered at term. Laparoscopic tubal reanastomosis is a well-established procedure with good prognosis, as reported in the literature. For women who wish to become pregnant after tubal sterilization, it is necessary to present the option of surgery as well as in vitro fertilization.

We assessed the clinical characteristics and perinatal outcome of disorders specific to monochorionic diamniotic (MD) twin pregnancies, focusing on twin-twin transfusion syndrome (TTTS) and related disorders, such as selective intrauterine growth restriction (sIUGR), inter-twin amniotic fluid discordance (AFD), and twin anemia polycythemia sequence (TAPS).We retrospectively reviewed 69 cases of MD twin pregnancies delivered after 22 weeks at our institution from January 2009 to September 2013.TTTS occurred in 9 cases (13%). There was a total of 11 cases (16%) of MD twins with sIUGR in this period. One case developed TTTS. All 3 cases (4%) of AFD in this study developed TTTS or sIUGR.AFD should be recognized as predictors of TTTS or sIUGR. Further studies on TTTS-related disorders allow a more precise subgroup categorization that enables optimal management.

After a FDA recommendation in April 2014, power morcellation (PM) in laparoscopic myomectomy (LM) has become less common. We now collect a myoma using manual morcellation (MM) from a wound in the umbilical region. In this study, we compared the PM and MM methods.The subjects were 69 patients who underwent LM from April 2013 to March 2016 using PM (n = 37) or MM (n = 32). With PM, the myoma was collected using a 4-hole 12-mm parallel trocar in the left lower abdomen. Using MM, an EZ ACCESSNone required allogeneic transfusion or a transition to open surgery, and had surgical or post surgical complications. At multiple linear regression analysis, which was adjusted by age, body mass index, and intraoperative blood loss, significant difference was not observed in operation time between the PM and MM groups.Manual morcellation was found to be a safe method for collection of myoma that prevents scattering of tissues and does not prolong the operation time.

Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome is characterized by congenital absence of the vagina and uterus. We conducted genome-wide SNP analyses and exome sequencing to detect the causes of MRKH syndrome. We identified de novo variants of MYCBP2, NAV3, and PTPN3 in three families and a variant of MYCBP2 in a sporadic case. Here, we demonstrated the partial genetic makeup of Japanese MRKH syndrome.

Uterine rupture in pregnancy can occur in patients with a history of uterine surgery such as myomectomy and Cesarean section. Here, we report a case of spontaneous uterine rupture that occurred in the early third trimester in a pregnant woman who had previously undergone laparoscopic removal of the right fallopian tube and interstitial portion for treatment of interstitial pregnancy. The patient presented with sudden onset of abdominal pain at 26 weeks of gestation. Detailed ultrasonography and magnetic resonance imaging led to diagnosis of uterine rupture. In emergency laparotomy, the fetus was delivered by Cesarean section, the placenta and membranes were removed, and the uterus was preserved with closure of the rupture and wound. This case highlights the importance of close follow-up of a pregnant patient who has previously had a uterine incision. The case also raises the question of whether the prevalence of uterine rupture may increase as more patients are treated with laparoscopic surgery of the uterus.