The purpose of the present study was to investigate whether pregnancy affects endothelin (ET)-1-induced contraction, the density ofET receptors, and the ratio of receptor subtypes (ET(A) and ET(B)) in uterine smooth muscle in humans. We also investigated which ET receptor subtypes mediate ET-1-induced contraction in the human uterus. In uterine membrane preparations, (125)I-labeled ET-1 ((125)I-ET-1) binding sites (Bmax) in pregnant women did not differ from those in age-matched nonpregnant women (596.2 +/- 107.1 vs. 512.1 +/- 167.7 fmol/mg protein). The dissociation constant (Kd) in pregnant women did not differ from that in nonpregnant women. Competitive displacement experiments with (125)I-ET-1 binding to the membranes using BQ-123 (ET(A) receptor antagonist) showed that the percentage of ET(A) receptors in uterine muscle was significantly higher in pregnant women than in nonpregnant women (P < 0.01). The calculated ratios of ET(A) to ET(B) receptors in pregnant and nonpregnant uteri were 92:8 and 68:32, respectively. Combination treatment with BQ-788 (ET(B) receptor antagonist) completely inhibited the BQ-123-resistant component of (125)I-ET-1 specific binding. ET-1 caused dose-dependent contractions in isolated human uteri from both pregnant and nonpregnant women. The maximum response was markedly greater in pregnant women than in nonpregnant women, whereas pD2 (-log[EC50]) values did not differ between pregnant and nonpregnant uteri. In pregnant human uterus, BQ-123 (10(-6) M) significantly shifted the dose-dependent curve of ET-1 response to the right, whereas BQ-3020 (ET(B) receptor agonist) did not cause contraction. These results suggested that ET-1-induced contraction of the human uterus is mediated through only ET(A) receptors and that ET-1-induced uterine contraction in humans is markedly increased during pregnancy. In addition, the present study suggests that, although (125)I-ET-1 Bmax are not altered during pregnancy, the proportion of ET(A) receptors is increased and that of ET(B) receptors is decreased in the pregnant human uterus.
Background Few reports have presented an overall view of pregnant women with coronavirus disease 2019 (COVID-19) across an entire country and throughout the entire gestation period. Furthermore, no such reports are available for Japan. We examined the clinical characteristics and outcomes of pregnant women with COVID‑19 on a national scale in Japan. Methods A nationwide questionnaire-based survey for all 2,185 maternity services in Japan was conducted between July and August 2020. Information regarding maternal characteristics and epidemiological, clinical, treatment, and perinatal outcomes of pregnant women diagnosed with COVID-19 between 16 January and 30 June 2020 were collected. Main outcome measures were incidence of pregnant women with COVID-19 and infant infection, positive rate of the universal screening test for asymptomatic pregnant women, identification of infection route and rates of maternal death, and severe cases. Results Responses from 1,418 institutions were assessed (65% of all delivery institutions in Japan). Seventy-two pregnant women were reported to have been diagnosed with COVID-19. The positive rate of the universal screening test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among asymptomatic pregnant women was 0.03% (2/7428). The most common route of infection was familial (57%). Fifty-eight pregnant women with COVID-19 were symptomatic, of whom five (8.6%) had a severe infection and one died (a tourist). Severe respiratory symptoms, oxygen administration, and pneumonia were frequently reported in the third trimester and postpartum period compared with in early pregnancy (22.2% vs 2.5% [P = 0.03], 38.9% vs 7.5% [P = 0.01], and 50.0% vs 7.5% [P < 0.001], respectively). All pregnant women with COVID-19 underwent caesarean sections, regardless of symptoms. There were no SARS-CoV-2 transmissions to newborns. Conclusions In Japan, the number of cases of COVID-19 infection in pregnant women is very low. Compared with early pregnancy, late pregnancy may be a risk factor for exacerbation of symptoms and familial transmission is the most common route of infection. The importance of infection prevention should be emphasised, especially in women in late pregnancy, their families, and any cohabitants.
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