Oxytocin receptors in the human uterus during pregnancy and parturition

We have determined the concentration and distribution of oxytocin receptors in myometrial and decidual tissues obtained at cesarean section or hysterectomy during pregnancy. Myometrial receptor concentration was low at 13 to 17 weeks but had risen about twelvefold by 37 to 41 weeks. After the onset of labor, either preterm or term, the receptor levels were maximal and significantly higher than before the onset of labor. In cases of failed induction of labor with oxytocin and in postterm pregnancies (43 to 46 weeks), the receptor concentration was significantly lower than in spontaneous labor. Myometrial receptor concentrations in the fundus and the corpus were similar and significantly higher than in the lower part of the uterine segment, and the cervix had the lowest concentration. The parietal decidua had oxytocin receptor concentrations of the same magnitude as the myometrium. These results are consistent with a functional role of endogenous oxytocin in the activation of the human uterus during pregnancy and parturition.     

Modulation of cell-to-cell coupling between myometrial cells of the human uterus during pregnancy.

OBJECTIVE: The purpose of this study was to investigate changes in cell-to-cell coupling of human myometrium during pregnancy to assess the presence and permeability of gap junctions. STUDY DESIGN: To evaluate the coupling, input resistance was measured and intercellular spread of Lucifer yellow was observed with microelectrode techniques in intact myometrial preparations from four nonpregnant women, 13 women not in labor, and three women in labor. Octanol, isoproterenol, and dibutyryl adenosine 3',5'-cyclic monophosphate were applied to the preparations to assess their effects on cell-to-cell coupling. RESULTS: Input resistance of myometrial cells was decreased (p less than 0.001) and intercellular spread of Lucifer yellow was increased during pregnancy. Octanol, isoproterenol, and dibutyryl adenosine 3',5'-cyclic monophosphate rapidly and reversibly increased input resistance (p less than 0.001 for all these agents) and blocked Lucifer yellow spread in tissues from pregnant patients. CONCLUSIONS: Cell-to-cell coupling between human myometrial cells is spontaneously improved during pregnancy because of the presence of gap junctions. The coupling is rapidly and reversibly decreased by octanol, isoproterenol, and dibutyryl adenosine 3',5'-cyclic monophosphate as a result of decreased permeability of gap junctions. These two methods of modulation of gap junctions are suggested to be major mechanisms for control of myometrial contractile activity in the human uterus during pregnancy.     

Adrenergic innervation of the human uterus. Disappearance of the transmitter and transmitter-forming enzymes during pregnancy.

The uterine adrenergic transmitter is in many animal species dramatically reduced during pregnancy, probably leading to a functional denervation near term. In order to clarify whether similar changes also occur in the human uterus, the adrenergic innervation of the isthmic myometrium during nonpregnant and pregnant conditions was analyzed by fluorescence histochemistry for demonstration of adrenergic nerves, and by quantitative measurements of norepinephrine and its synthesizing enzymes, tyrosine hydroxylase and dopa decarboxylase. At term pregnancy all fluorescent adrenergic nerves in the myometrium had disappeared, and the norepinephrine concentration had been reduced to almost zero. Parallel to this the activities of tyrosine hydroxylase and dopa decarboxylase were markedly reduced. By contrast, the activity of the acetylcholine-synthesizing enzyme, choline acetyltransferase, was unchanged, indicating that the adrenergic system was selectively affected. The results confirm that the adrenergic nerves in the human uterus, like those in uterine horns of laboratory animals, undergo fundamental changes in the course of pregnancy. This probably reflects entirely different conditions for a sympathetic influence on the myometrium during the last two trimesters of pregnancy compared to the non-pregnant situation.     

Early human pregnancy in vitro utilizing an artificially perfused uterus

The penetration of luminal epithelium in the uterine cavity represents the crucial event that triggers the failure of embryo implant, thus limiting the possibility of fertility control. The purpose of our study was to implant a human blastocyst, cultured in vitro, into a human uterus extracorporeally perfused with an oxygenated medium. For this purpose, human blastocysts, collected from patients who underwent IVF program because of irreparable tubal infertility, were injected under the luminal epithelium of human perfused uteri. Light and electron microscopy showed that human blastocyst can successfully undergo the stage of implantation and trophoblastic invasion in 52 hours of extracorporeal perfusion.     

The change in tenascin expression in mouse uterus during early pregnancy

Purpose: Our aim was to examine the changes in spatiotemporal tenascin (TN) expression in mouse uterus during early pregnancy, when the uterine tissue undergoes a tremendous restructuring. Methods: Using immunohistochemistry and in situ hybridization, the changes in distribution of TN protein in mouse uterine tissues in pregnancy Day 0 through Day 5 were analyzed. Results: Immunoreactive TN and TN mRNA were expressed in the basement membrane of the epithelium as well as in the smooth muscle layer, and their distribution shifted from the subbasement region on Day 0–3 to the smooth muscle layer on Days 4 and 5. Conclusions: These results indicate that TN expression in the uterus during early pregnancy is spatiotemporally different and may be regulated by a different mechanism.     

妊娠期免疫系统的特点与妊娠合并自身免疫性疾病

妊娠是一个复杂的生理过程，其中免疫系统发生的一系列改变，是维持母体对胎儿这一"非己"成分的免疫耐受以及对外界刺激的正常应答。同时，在妊娠过程中某些自身免疫性疾病的发病率增加，或已经稳定的疾病在妊娠期间出现疾病活动或病情恶化，也与妊娠期间免疫系统的特殊变化密切相关。但其在妊娠期发生的确切机制尚不明确，本文通过复习文献对妊娠期免疫系统的变化特点及妊娠期合并自身免疫性疾病的免疫学基础进行讨论。     

Innate immune cell recruitment in the fetus and neonate

Recruitment of innate immune cells from the vasculature into infected tissue is a key event in primary host defense against invading pathogens. This highly regulated process requires a functional interplay of specialized adhesion molecules and involves a series of steps leading from rolling of leukocytes along the endothelium to firm adhesion and finally transmigration. In the developing fetus, innate immune functions are ontogenetically regulated and show increasing maturation throughout gestation. Developmental differences in the innate immune response leave the neonate and especially the premature newborn at high risk of severe infections. Understanding the ontogeny of immune functions in the fetus and newborn is therefore essential for the prevention and treatment of neonatal infections. In this review, an overview will be given of the developmental aspects of innate immune cell recruitment including a discussion of controversial findings and open questions.     

Characterisation of the humoral immune response during murine pregnancy

Blood samples from female C57BL/10 mice mated with CBA/Ca males were obtained before, during and after both first and second pregnancies. A cellular enzyme-linked immunospecific assay (CELISA) was used to detect maternal antibodies against antigens on paternal splenocytes. Alloantibodies were detected in 48% of mice during or 9 days after a first pregnancy and in 82% of mice by the ninth day after the second pregnancy; these antibodies were first observed on day 10 of the first pregnancy. In two of four active multigravid sera tested, an increase in IgG1 concentration was detected; the level of all other isotypes remained within normal limits. Weak binding of alloantibody to an antigen of approximate molecular weight 44,000 was detected on CBA/Ca splenocytes by immunoblotting sera from multiparous animals. These sera also recognised an antigen of similar molecular weight on H-2b identical 129J splenocytes but not on splenocytes from the maternal strain. These results provide further information on the maternal humoral immune response during murine pregnancy.     

Diffuse cavernous hemangioma of the uterus diagnosed during pregnancy. Case report

We report the case of a pregnancy of 16 weeks with anemia and a presumptive diagnosis of partial mole. In secondary care this diagnosis was ruled out through ultrasonography and diffuse cysts were found in the myometrium. Spectral Doppler ultrasound showed no flow, but it could be observed with power angiography. Cesarean section was performed at 38 weeks and hysterectomy 24 hours after because of intra-abdominal hemorrhage. Power angiography, spectral Doppler and serum human chorionic gonadotropin are the most useful diagnostic tools in the differential diagnosis of diffuse cavernous hemangioma of the uterus. Postpartum hemorrhage is a likely complication.     

Changes in immune activation markers during pregnancy and postpartum

Changes in CD4 + cell levels and other immune parameters have been reported to occur during pregnancy but the timing of these alterations and their relationship to changes in immune function have not been well characterized. In addition, the influence of sociodemographic, obstetric, and other covariates on these relationships is largely unknown. We measured three immune activation markers, soluble interleukin-2 receptor (sIL-2Ralpha), soluble CD8 antigen (sCD8), and neopterin during pregnancy and postpartum in 170 HIV-1-seronegative women enrolled in the Mothers and Infants Cohort Study. Ante-partum and postpartum changes in these markers were examined using multivariable longitudinal random effects models. Neopterin levels began to rise well before delivery and were in decline by 2 months postpartum. sIL-2Ralpha and sCD8 levels increased at or near delivery and peaked by 2 months postpartum. After adjustment for other variables, the peak in sIL-2Ralpha was greater among women with pre-term than full-term deliveries (P = 0.05). All three markers were higher in whites than non-whites and in 'hard' drug users than non-users (P < or = 0.001 for each). After adjustment for these and other variables, hepatitis C virus (HCV) seropositivity was associated with higher levels of sCD8 and neopterin (P < or = 0.001 for each) but not sIL-2Ralpha (P = 0.27). These longitudinal data indicate that a state of broad immune activation develops at or near delivery. A number of maternal variables appear to influence the magnitude of these changes.