Fetoplacental regional variations in the expression of angiopoietin-1, angiopoietin-2, and Tie2 in normal-term and near-term pregnancies

Background: Angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), and the receptor tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2) are known to be involved in fetoplacental angiogenesis adequacy, which is a primary determinant of fetal growth. Regional variations in Ang1, Ang2, and Tie2 remain unknown, although fetoplacental vascularity and gene expressions differ between the placental center and the periphery.

Objective: The aim of this study was to test the hypothesis that there are regional variations in the expression of these angiopoietins in human placentas from uncomplicated term and near term pregnancies.

Study design: In this prospective study, central and peripheral samples were collected from fresh placentas from normal-term and near-term pregnancies delivered by Cesarean section (n?=?7, 36–41 week gestation) prior to the onset of labor. Regional differences in Ang1, Ang2, and Tie2 protein expressions were measured by Western blot and densitometric analyses with b-actin normalization, and their fetoplacental regional localization assessed by immunohistochemistry. The Ang1 and Ang2 ratios at central and peripheral sites were determined. Statistical analysis was performed using Student’s t-test.

Results: Ang1 protein expression was higher in the placental periphery than in the center (2.48?±?0.42 versus 1.74?±?0.27, p?=?0.01). In contrast, Ang2 protein expression was greater in the placental center than in the periphery (10.10?±?1.82 versus 7.15?±?1.12, respectively, p?=?0.03). The Ang1–Ang2 ratio reflected these differential expressions. Tie2 protein expression was higher in the placental periphery than in the center (0.21?±?0.02 versus 0.16?±?0.02, p?=?0.003). The immunoreactivity of Ang1 and Tie2 was stronger in the periphery than in the center, and that of Ang2 was stronger in the center than in the periphery.

Conclusions: Ang1, Ang2, and Tie2 are differentially expressed in placental center and periphery. Ang1/Ang2 ratio reflects this regional variation in the angiogenic balance that has implications for fetoplacental villous angiogenesis. The results also demonstrate the importance of considering the location of placental sampling sites for any future investigations of fetoplacental villous angiogenesis.     

围产新生儿SARS-CoV-2感染临床观察研究方案专家建议

严重急性呼吸综合征冠状病毒2(Severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)感染流行,但因目前新生儿病例报道较少,证据资料欠完善,对新生儿SARS-CoV-2感染的途径、临床特征、治疗及预后甚至诊断标准等认识尚不清楚和统一,故围产界应积极对围产儿SARS-CoV-2感染进行系统全面研究,因为这些临床资料、统计数据和研究结果将对于此次乃至今后冠状病毒感染在这些最脆弱特殊人群防治具有十分重要的意义。为此,中国医师协会新生儿科医师分会循证学组、中华医学会围产医学分会重症学组联合组织专家组研制本建议,供围产学界同行拟定该方面具体项目计划参考。     

Distribution of cyclooxygenase-1, cyclooxygenase-2, and cytosolic phospholipase A2 in the luteal phase human endometrium and ovary

OBJECTIVE: To identify the distribution of the enzymes cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and cytosolic phospholipase A(2) (cPLA(2)) in the human ovary and endometrium. DESIGN: Prospective clinical study. SETTING: Hospital-based unit for reproductive health and research laboratories. PATIENT(S): Twenty-nine healthy fertile women with normal menstrual cycles. INTERVENTION(S): Endometrial and ovarian biopsy samples were obtained from healthy, fertile women in the luteal phase of the menstrual cycle or during caesarean section. MAIN OUTCOME MEASURE(S): Pinopode formation and immunohistochemical staining of cPLA(2), COX-1, and COX-2. RESULT(S): In the endometrium, the immunostaining of cPLA(2) was most intense in the luminal epithelium when pinopodes were present. The staining of both COX-1 and COX-2 was most intense in the epithelial cells, with the stroma staining positive only for COX-2. The endometrial vessels expressed COX-2 but not COX-1. The staining of COX-1 and COX-2 was intense on the surface epithelial cells on the outer lining of the ovary. CONCLUSION(S): This study details the distribution of these prostaglandin synthase enzymes and emphasizes their importance for the functions of both the endometrium and the ovary.     

Maternal and fetal outcomes of the pregnant woman with COVID-19: The first case report in Taiwan

ObjectiveA real-Taiwan experience to deal with near-term pregnant woman infected by severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 (coronavirus disease 2019, COVID-19) is extremely limited. We described the first case in Taiwan.Case reportA 30-year-old woman, primigravida had a laboratory-confirmed COVID-19 infection at 36 gestational weeks (GW). She was asymptomatic. Ten days later, she was hospitalized and receive a selective cesarean section with a term baby weighted 3142 gm (Apgar score 8 and 9 at 1st and 5th minute, respectively) at 38 GW. No evidence of in utero and direct transmission was found and newborn was free of COVID-19.ConclusionIt is still uncertain whether timing or mode of delivery is appropriate in SARS-CoV-2 infected pregnant woman in near term, but we suggested that a selective delivery time at 38 GW or later, regardless of which mode of delivery is finally decided, can be considered.     

SARS-CoV-2 infection among healthcare workers whom already received booster vaccination during epidemic outbreak of omicron variant in Taiwan

Background/PurposeHealthcare workers (HCWs) are at risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to occupational exposure. We aim to investigate the prevalence and risk factors of SARS-CoV-2 infection among HCWs during epidemic outbreak of omicron variant in Taiwan.MethodsSequential reserved serum samples collected from our previous study during December 2021 and July 2022 were tested for antibodies against SARS-CoV-2 nucleocapsid protein (NP). Diagnosis of SARS-CoV-2 infection was defined as positive either of anti-SARS-CoV-2 nucleoprotein, rapid antigen test or polymerase chain reaction. Retrospective chart review and a questionnaire were used to access the symptoms and risk factors for SARS-CoV-2 infection.ResultsTotally 300 participants (69.3% female) with a median age of 37.9 years were enrolled. A significant increase incidence of SARS-CoV-2 infection was found before and during community outbreak (11.91 versus 230.93 per 100,000 person-days, P < 0.001), which was a trend paralleling that observed in the general population. For 61 SARS-CoV-2 infected participants, nine (14.8%) were asymptomatic. Multivariate analysis revealed recent contact with a SARS-CoV-2 infected household (odds ratio [OR], 7.01; 95% confidence interval [95% CI], 3.70–13.30; P < 0.001) and co-existed underlying autoimmune diseases (OR, 4.46; 95% CI, 1.28–15.51; P = 0.019) were significant risk factors associated with acquisition of SARS-CoV-2 infection among HCWs.ConclusionCommunity factors, such as closely contact with SARS-CoV-2 infected individuals and underlying immune suppression status, were significant factors for acquisition of SARS-CoV-2 infection among HCWs. We suggest the application of appropriate infection control measures for HCWs should be maintained to reduce risk of SARS-CoV-2 infection.     

Expression and clinical significance of vascular endothelial growth factor,cyclooxygenase-2, and Bcl-2 in borderline ovarian tumors

Objective The objectives were to study the expression of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (Cox-2), and Bcl-2 in borderline ovarian tumors (BOTs) and the relationship within them, and to investigate the correlation between expression of VEGF, Cox-2, and Bcl-2, and the clinicopathologic features of BOTs.Methods An immunohistochemical technique was used to investigate the expression of VEGF ,Cox-2, and Bcl-2 in 69 borderline, 18 benign, and 27 malignant human ovarian tumor tissues.Results Expression rate of VEGF protein (59.4%) in BOTs was higher than in benign tumors (27.8%) and was lower than in ovarian carcinomas (92.6%), and there was a significant difference between BOTs and benign ovarian tumors (p<0.05), and carcinoma (p<0.01). Significant correlation was observed between the positive expression rate for VEGF and clinical stage of BOTs (p<0.05). The statistical analysis did not show a close correlation between the expression of VEGF and tissue type, and peritoneal implants in BOTs (p>0.05). The expression rate of Cox-2 was significantly higher in ovarian carcinomas (81.5%) than in BOTs (57.9%) and in benign ovarian tumors (38.9%) (p<0.05). Significant correlation was observed between the positive expression rate for Cox-2 and the clinical stage of BOTs (p<0.05). The statistical analysis showed no close correlation between the expression of Cox-2 and tissue type, and peritoneal implants in BOTs (p>0.05). There was a significant difference between the expression of Bcl-2 in ovarian carcinomas and BOTs than that in benign ovarian tumors (p<0.05). The positive expression rate of Bcl-2 was not related to clinical stages and peritoneal implants (p>0.05). Statistical analysis showed a positive correlation between the expression of Cox-2 and VEGF, and Bcl-2 in BOTs.Conclusions Overexpression of VEGF, Cox-2, and Bcl-2 in BOTs may play an important role in the oncogenesis and progression of BOTs. It is feasible to detect VEGF, Cox-2, and Bcl-2 in the diagnosis and to predict the prognosis of BOTs.     

Matrix metalloproteinase-2, membranous type 1 matrix metalloproteinase,and tissue inhibitor of metalloproteinase-2 expression in ectopic and eutopic endometrium

OBJECTIVE: To investigate expression of matrix metalloproteinase-2 (MMP-2), membranous type 1 matrix metalloproteinase (MT1-MMP), and tissue inhibitor of metalloproteinase-2 (TIMP-2) in ectopic and eutopic endometrium from women with and without endometriosis throughout the menstrual cycle. DESIGN: Molecular studies in human tissue. SETTING: Reproductive immunology laboratory of a university medical center. PATIENT(S): Fifty-three premenopausal woman (23 with endometriosis and 30 without endometriosis) undergoing laparoscopic surgery. Endometrium and ectopic endometriosis tissue were obtained at the time of surgery. MAIN OUTCOME MEASURE(S): Messenger RNA and protein expression from eutopic and ectopic endometrium was analyzed by using quantitative competitive polymerase chain reaction, zymography, and Western blot assay. RESULT(S): Uterine endometrium from women with endometriosis expressed higher levels of MMP-2 and MT1-MMP and lower levels of TIMP-2 than did endometrium from normal women. CONCLUSION(S): Eutopic endometrium from patients with endometriosis may be more invasive and prone to peritoneal implantation because of greater expression of MMP-2 and MT1-MMP and lower expression of TIMP-2 messenger RNA, compared with endometrium from women without endometriosis. Thus, increased proteolytic activity may help to explain the invasive factors that result in endometriosis.     

Emx2和Emx2OS在小鼠胚胎生殖嵴中的表达

目的:探讨转录因子Emx2和Emx2反义非编码长链RNA(EMX2 opposite strand/antisense RNA,Emx2OS)在小鼠生殖嵴发育过程中的表达模式以及对原始生殖细胞发育的作用。方法:分别收集孕11.5~14.5 d小鼠的生殖嵴,通过原位杂交、qRT-PCR和免疫荧光方法,观察分析Emx2和Emx2OS在生殖嵴中的表达定位及其表达水平的变化。结果:在孕11.5~14.5 d雌性和雄性小鼠胚胎生殖嵴中均检测到Emx2OS的表达,而且其表达模式与Emx2高度一致;在小鼠胚胎原始生殖细胞减数分裂的启动以及性别决定的时间点(孕12.5 d),雌性胎小鼠生殖嵴中Emx2和Emx2OS的表达量都显著上调(P0.001)。结论:Emx2和Emx2OS在胎小鼠生殖嵴中呈同步表达模式,并可能参与调控原始生殖细胞减数分裂的启动。     

Oxytocin,PGE2 and PGF2α stimulate the production of inositol phosphates in the rabbit myometrium

Summary Phosphoinositide breakdown is thought to be important in regulating a variety of transmembrane signal transduction in the action of oxytocic agent during uterine smooth muscle contraction. We investigated the effects of oxytocin and prostaglandins (PGE₂ and PGF_2α) on phosphoinositide hydrolysis in the myometrium taken from non-pregnant and pregnant rabbits by measuring the accumulation of total inositol phosphates (IP). Oxytocin strongly, and PGE₂ and (PGF_2α) slightly but significantly, stimulated IP production in both the non-pregnant and pregnant myometria. Oxytocin more markedly accelerated the IP production in pregnant myometrium than in non-pregnant myometrium. However, IP production stimulated by PGE₂ and PGF_2α was much the same in non-pregnant and pregnant myometria. The amount and time course of the increase in the production of the total IPs by oxytocin are quite different from those by PGs. It seems that the mechanism by which oxytocin stimulates phospholipase C is different from that of the PGs. It is suggested that transmembrane signalling pathways of phosphoinositide hydrolysis play an important role in the each mechanism.     

PTEN与bcl-2、FasL在异位子宫内膜的表达及临床意义

目的:研究PTEN与bcl-2、FasL的表达与异位子宫内膜的关系。方法:用免疫组化法检测PTEN与bcl-2、FasL在正常子宫内膜,异位内膜及在位内膜的表达。结果:(1)正常子宫内膜组:bcl-2在增生期的表达显著高于分泌期(P0.05),FasL及PTEN在增生期的表达显著低于分泌期(P0.05),即三者在正常子宫内膜细胞的表达均有明显周期性;(2)异位内膜组(OEM及AM):bcl-2、FasL及PTEN的表达在增生期和分泌期的表达均无统计学差异(P0.05)。即在异位子宫内膜中的bcl-2、FasL及PTEN呈持续表达且失去周期性;(3)在位内膜组(OEM及AM):与正常子宫内膜组相似,三者在增生期和分泌期的表达均有差异,其中,FasL与PTEN在分泌期的表达高于增生期,bcl-2在增生期的表达则高于分泌期,差异均有统计学意义(P0.05);(4)3组内膜中的表达比较:FasL及bcl-2在异位内膜组的表达均高于在位内膜组及正常子宫内膜(P0.05),PTEN在异位内膜组的表达均低于在位内膜组及正常子宫内膜(P0.05);FasL、bcl-2及PTEN在正常内膜组的表达与在位内膜组无统计学差异(P0.05)。结论:bcl-2、FasL及PTEN的表达变化在子宫内膜异位症的发生发展过程中起着重要作用。     

Bax,Bcl-2, and p53 expression in endometrial cancer

BACKGROUND: It has not been fully clarified whether alteration of Bax and other apoptosis-relating proteins of Bcl-2 and p53 is involved in endometrial carcinogenesis. METHODS: A total of 56 frozen tissues, which included 14 normal endometria, 13 endometrial hyperplasias (10 without atypia and 3 with atypia), and 29 endometrial carcinomas, were examined for the expression of Bax, Bcl-2, and p53 using immunohistochemistry. For Bax-negative cases, PCR-direct sequencing was performed for the bax gene. For cases with p53 overexpression, mutational analysis was performed for the p53 gene using a yeast functional assay and sequencing. RESULTS: Both Bax and Bcl-2 were distinctly expressed in the normal proliferative phase endometrium. A decreased Bcl-2/Bax ratio in the secretory phase endometrial gland cells due to suppressed Bcl-2 expression was observed. Bax expression was positive in all 13 endometrial hyperplasias, while it was absent in 6 of 29 endometrial carcinomas (20.7%). Negative Bax expression in endometrial carcinoma was not related to tumor stage, histologic subtype, or other histopathologic prognostic factors. Bax expression showed no relationship to either p53 overexpression or Bcl-2 expression. In the DNA of 6 Bax-negative cases, we found a frameshift insertion mutation at codon 58 (AAG to CAAG) in the BH3 domain despite the absence of mutation in the (G)8 tract, suggesting that this codon may be another preferred target for bax mutation other than the (G)8 tract. Mutational analysis was available for 7 of 10 cases with p53 overexpression, in which 5 cases were found to have a missense mutation and 2 cases had no mutation of the p53 gene. At least 10 of 29 (34.5%) cases of endometrial carcinoma were associated with sequence-verified mutation in the bax gene and/or p53 gene. CONCLUSIONS: The bax gene frameshift mutation appears to cause a loss of Bax expression in endometrial carcinoma. Codon 58 may be a preferred target of bax gene mutation in endometrial carcinomas. The bax gene mutation seems to occur in the early stage of the genesis of a subset of endometrial carcinomas.     

EMX2、HOXA10与子宫内膜容受性

胚胎与子宫内膜的同步发育是着床的必要条件,而在着床窗期间,胚泡滋养外胚层侵入和妊娠建立的关键是子宫内膜具有容受性。近年从分子机制研究子宫内膜容受性取得很大进展,学者们发现了与子宫内膜容受性有关的一些基因。本文主要从同源结构域基因EMX2和HOXA10在子宫内膜的表达和对子宫内膜容受性的影响进行综述。     

Relationship of lactation,BMI, and rs12255372 TCF7L2 polymorphism on the conversion to type 2 diabetes mellitus in women with previous gestational diabetes

Abstract

Women with previous gestational diabetes mellitus (pGDM) have a high risk of developing postpartum type 2 diabetes mellitus (T2DM). This study aimed to analyze the relationship between lactation, BMI, and TCF7L2 polymorphisms in the conversion to T2DM in women with pGDM. One hundred and fifty-three women con pGDM were recruited from public hospitals of León Guanajuato México. Three groups: normal glucose tolerance (NGT), impaired glucose intolerance (IGT), and T2DM after the oral glucose tolerance test were formed. Metabolic and hormone variables were measured, and genotyping was made by PCR-RFLP. The questionnaire included data on lactation (yes/no), duration of lactation, and full lactation. After 35 (21–49) months from the last partum, 54% of women had an NGT, 30.7% IGT, and 15% T2DM. BMI and rs12255372 are associated with the risk of conversion to IGT and T2DM [OR?=?1.07 (95% IC 1.0–1.14, p?=?.041; OR =2.14, 95% IC 1.01–4.55, p?=?.04 respectively), while the lactation shows a strong protective effects OR?=?0.15 (95% IC 0.062–0.39, p?=?.00007), and an apparent interaction with rs12255372T decreasing the risk in carriers (OR =2.15; 95% IC 0.97–4.7, p?=?.05). BMI is an independent risk factor of IGT/T2DM development. The lactation shows a strong protective effect and a possible interaction with rs12255372 polymorphism.     

Expression of HER-2/neu, epidermal growth factor receptor, vascular endothelial growth factor, cyclooxygenase-2, estrogen receptor, and progesterone receptor in small cell and large cell neuroendocrine carcinoma of the uterine cervix: a clinicopathologic and prognostic study

We studied the immunohistochemical expression of HER-2/neu, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), estrogen receptor (ER), and progesterone receptor (PR) in uterine cervical small cell and large cell neuroendocrine carcinomas (SCNECs and LCNECs) from 24 patients seen at The University of Texas M.D. Anderson Cancer Center. The objectives were to determine their expression and prognostic role in survival. Twenty-three cases (95.8%) expressed VEGF. The tumors expressing EGFR, HER-2/neu, and COX-2 were modest in numbers: eight (33.3%), 10 (41.7%), and seven (29.2%), respectively. Only one tumor (4.2%) expressed ER, and only two tumors (8.3%) expressed PR. No significant differences in the expression of these factors were found between SCNECs and LCNECs or between stage I and stage II-III tumors. The median overall survival was 21.1 months (95% confidence interval [CI], 17.2-25.0 months). Only HER-2/neu expression was significantly associated with survival. Patients with negative HER-2/neu expression tumors had significantly shorter survival than those whose tumors were positive, 14.2 months (95% CI, 10.6-17.7 months) versus 33.1 months (95% CI, 0-76.92 months) (P = 0.03). There was a trend toward worse survival in patients with EGFR expression, but this finding was not significant. The combination of negative HER-2/neu expression and positive EGFR expression had the worst impact on survival.     

金属基质蛋白酶(MMP-2)及其激动剂和抑制剂在输卵管黏膜上皮的表达与输卵管妊娠的关系

目的:探讨基质金属蛋白酶-2(MMP-2)和膜型MMP(MT1-MMP)及其组织抑制剂TIMP-2与输卵管妊娠的关系。方法:运用免疫组化结合病理图像半定量分析方法,检测32例正常输卵管壶腹部标本(A组)、32例输卵管炎壶腹部标本(B组)、26例输卵管壶腹部妊娠标本(C组)中MT1-MMP、MMP-2及TIMP-2的表达情况。结果:TIMP-2在A组输卵管黏膜中表达最高,与B组、C组比有统计学差异,B、C组间比较无差异。MMP-2,MT1-MMP表达强度与TIMP-2相反,A组最低,B组的表达最高,C组的表达略低于B组,组间两两比较均有统计学差异(P<0.05)。结论:输卵管的慢性炎症会引起MMP-2的激动剂MT1-MMP表达增强,MMP-2/TIMP-2之间的动态平衡失衡,从而可能参与了输卵管妊娠的发生。