Kidney-tonifying and Blood-activating Prescription Regulates Wnt/β-catenin Signaling Pathway to Improve Uterine Spiral Artery Remodeling in Mouse Model of Recurrent Miscarriage / 中国实验方剂学杂志

ObjectiveTo observe the effects of the kidney-tonifying and blood-activating prescription on the Wnt/β-catenin signaling pathway and uterine spiral artery remodeling in a mouse model of recurrent miscarriage and to explore its underlying mechanism. MethodA mouse model of normal pregnancy was established by mating CBA/J mice with BALB/c mice. A mouse model of recurrent miscarriage was established by mating CBA/J mice with DBA/2 mice. The modeled mice of recurrent miscarriage were randomized into model， dydrogesterone， and low- and high-dose Chinese medicine groups. The mice in normal pregnancy were used as the control group. Each group consisted of 10 mice， and the drug administration lasted for 14 days. After the treatment， the embryo absorption rate of each group was recorded. Hematoxylin-eosin （HE） staining was employed to observe the pathological morphology of the uterine decidua， and the physiological transformation rate of spiral arteries （SPA） was evaluated. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to determine the mRNA and protein levels， respectively， of matrix metalloproteinases （MMP）-2， MMP-9， vascular endothelial growth factor （VEGF）， and Wnt/β-catenin signaling pathway. ResultCompared with the control group， the model group presented increased embryo absorption rate （P<0.05）， decreased physiological transformation rate of uterine SPA （P<0.05）， cellular swelling， degeneration， and disordered arrangement in the uterine decidua tissue， and down-regulated mRNA and protein levels of key factors involved in SPA remodeling （MMP-2， MMP-9， VEGF） and the Wnt/β-catenin signaling pathway （Wnt2， β-catenin， Cyclin D1， c-Myc） （P<0.05）. Compared with the model group， both the low- and high-dose Chinese medicine reduced embryo absorption rate （P<0.05）， increased SPA physiological transformation rate （P<0.05）， improved uterine decidua tissue morphology， and increased decidua vessel count. Furthermore， they up-regulated the mRNA and protein levels of MMP-2， MMP-9， VEGF， and proteins in the Wnt/β-catenin signaling pathway （P<0.05）. ConclusionRecurrent miscarriage is associated with impaired uterine spiral artery remodeling. The kidney-tonifying and blood-activating prescription can promote uterine spiral artery remodeling by activating the Wnt/β-catenin signaling pathway and promoting the expression of VEGF， MMP-2， and MMP-9， thus treating recurrent miscarriage.

Expression of lncRNA TGFB2-AS1 in the placenta of preeclampsia and its relationship with placental spiral artery recasting / 中华内分泌外科杂志

Objective:To investigate the relationship between the expression level of long non-coding RNA transforming growth factor β2-antisense RNA1 (lncRNA TGFB2-AS1) and placental spiral artery recasting in the placenta of preeclampsia.Methods:A total of 108 pregnant women with severe preeclampsia who were hospitalized in Zaozhuang Maternal and Child Health Hospital and delivered by cesarean section from Oct. 2019 to Jun. 2021 were selected as the research objects, and they were divided into the late-onset preeclampsia group (late-onset severe preeclampsia pregnant women, 56 cases) and early-onset preeclampsia group (early-onset severe preeclampsia pregnant women, 52 cases) ; at the same time, 58 normal pregnant women were selected as the normal pregnancy group. The general data of pregnant women were collected, such as age, systolic blood pressure and diastolic blood pressure. Real-time fluorescent quantitative PCR (qRT-PCR) method was used to detect the expression level of lncRNA TGFB2-AS1 in placental tissues, a scanning electron microscope was used to measure the lumen area and wall thickness of spiral arteries. Pearson correlation analysis method was used to analyze the correlation between the level of lncRNA TGFB2-AS1 in the placenta tissue and the thickness of the spiral artery wall and the area of the lumen of pregnant women with early-onset and late-onset severe preeclampsia.Results:The tube wall thickness [ (119.69±8.31) μm], systolic blood pressure [ (162.86±4.94) mmHg], diastolic blood pressure [ (103.09±2.35) mmHg], and 24-hour urine protein [ (2.17±0.31) g/24 h] in the early preeclampsia group were higher than those in the late preeclampsia group [ (101.04±5.78) μm, (146.95±6.43) mmHg, (92.13±4.74) mmHg, (1.62±0.23) g/24 h] and the normal pregnancy group [ (99.82±5.56) μm, (116.42±9.31) mmHg, (74.25±6.74) mmHg, (0.06±0.02) g/24 h], the placental tissue lncRNA TGFB2-AS1 level (0.62±0.16), lumen area [ (133.74±20.16) μm 2], gestational week of delivery [ (32.15±1.74) weeks], weight of the newborns [ (2.25±0.26) g] were lower than those in the late-onset preeclampsia group [ (0.99±0.21), (185.49±22.75) μm 2, (36.14±1.59) weeks, (3.37±0.32) g] and the normal pregnancy group [ (1.02±0.23), (186.42±23.71) μm 2, (38.19±1.56) weeks, (3.42±0.37) g] ( P<0.05). The systolic blood pressure, diastolic blood pressure, and 24-hour urine protein in the late preeclampsia group were higher than those in the normal pregnancy group, gestational week of delivery was lower than the normal pregnancy group ( P<0.05). Placental tissue lncRNA TGFB2-AS1 of pregnant women with early-onset severe preeclampsia was positively correlated with the lumen area, and negatively correlated with the thickness of the tube wall ( P<0.05). There was no correlation between lncRNA TGFB2-AS1 and the lumen area and wall thickness in the placental tissue of pregnant women with late-onset severe preeclampsia ( P>0.05) . Conclusion:The lncRNA TGFB2-AS1 expression in the placenta tissue of pregnant women with early-onset severe preeclampsia is abnormally low, which may be related to the insufficient recasting of the placental spiral artery.

Acute Atherosis of the Uterine Spiral Arteries: Clinicopathologic Implications

Acute atherosis is unique vascular changes of the placenta associated with poor placentation. It is characterized by subendothelial lipid-filled foam cells, fibrinoid necrosis of the arterial wall, perivascular lymphocytic infiltration, and it is histologically similar to early-stage atherosclerosis. Acute atherosis is rare in normal pregnancies, but is frequently observed in non- transformed spiral arteries in abnormal pregnancies, such as preeclampsia, small for gestational age (SGA), fetal death, spontaneous preterm labor and preterm premature rupture of membranes. In preeclampsia, spiral arteries fail to develop physiologic transformation and retain thick walls and a narrow lumen. Failure of physiologic transformation of spiral arteries is believed to be the main cause of uteroplacental ischemia, which can lead to the production of anti-angiogenic factors and induce endothelial dysfunction and eventually predispose the pregnancy to preeclampsia. Acute atherosis is more frequently observed in the spiral arteries of the decidua of the placenta (parietalis or basalis) than in the decidual or myometrial segments of the placental bed. The presence and deeper location of acute atherosis is associated with poorer pregnancy outcomes, more severe disease, earlier onset of preeclampsia, and a greater frequency of SGA neonates in patients with preeclampsia. Moreover, the idea that the presence of acute atherosis in the placenta may increase the risk of future cardiovascular disease in women with a history of preeclampsia is of growing concern. Therefore, placental examination is crucial for retrospective investigation of pregnancy complications and outcomes, and accurate placental pathology based on universal diagnostic criteria in patients with abnormal pregnancies is essential for clinicopathologic correlation.

Predicting Endometrium Receptivity with Parameters of Spiral Artery Blood Flow / 华中科技大学学报（医学）（英德文版）

Summary: In order To evaluate whether the parameters of spiral artery blood flow, as measured by transvaginal color Doppler, may be used to assess endometrium receptivity prior to embryo transfer (ET), a retrospective study of 94 infertile women who had undergone ART treatments with different outcomes (pregnant or nonpregnant) was done. Subendometrial blood flow was evaluated. The resistance index (RI), systolic/diastolic ratio (S/D) and pulsatility index (PI) were significantly lower in those who achieved pregnancy as compared with those who did not: 0.62±0.04 vs 0.68±0.04 (P＜0.001), 2.66±0.33 vs 3.19±0.39 (P＜0.01) and 1.15±0.17 vs 1.34±0.22 (P＜0.05), respectively. Furthermore, when RI>0.72, PI>1.6, and S/D>3.6, no pregnancy occurred. These data suggest that the parameters of spiral artery blood flow could be used as a new assay in predicting endometrial receptivity before ET.