Potential role of decidual apoptosis in the pathogenesis of miscarriages

To investigate the existence and the distribution of decidual apoptosis in normal pregnancies and miscarriages (spontaneous and recurrent), a comparative immunofluorescent tissue labelling of normal control (n?=?12) and miscarried pregnancies (n?=?24) was designed. Evaluation of the existence and distribution of decidual apoptosis in normal pregnancies and miscarriages, characterization of the apoptotic cell types and the involvement of caspase-dependent pathways was analyzed with TUNEL, anti-active caspase-3, anti-pancytokeratin and anti-CD45 antibodies. Normal decidua showed few apoptotic cells, whereas decidua from recurrent miscarriages had a significantly higher number of apoptotic cells preferentially localized to the sub-epithelial and periarteriolar regions, where the onset of decidualization occurs. Apoptosis occurred via a caspase-dependent pathway. Neither immune nor epithelial cells were positively stained for any apoptotic markers. The increased number of apoptotic cells, which are strictly restricted to the periarteriolar stroma particularly in recurrent miscarriages leads us to suggest that decidual apoptosis could result a series of cellular dysfunctions that may threaten the course of pregnancy.     

Possible role of bacterial and viral infections in miscarriages

OBJECTIVE: To determine the role of infections in miscarriages. Chorionic villi from aborted material were subjected to cytogenetic evaluation and analyzed for the presence of Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, human cytomegalovirus (HCMV), adeno-associated virus (AAV), and human papillomaviruses (HPV). DESIGN: Retrospective study. SETTING: University hospital and academic research institution. MAIN OUTCOME MEASURE(S): Karyotyping and detection of bacterial and viral DNA by means of polymerase chain reaction (PCR) in placenta specimens. RESULT(S): In 54 (50%) of 108 samples the karyotype was normal, in 38 (35%) samples it was abnormal, and in 16 (15%) samples karyotype was undetermined. No U. urealyticum, M. hominis, HCMV, or AAV-2 DNA was detected, while C. trachomatis DNA was detected in one (1%) and HPV DNA in eight (7%) samples. No significant correlation of HPV-positive findings with karyotype status was established. CONCLUSION(S): Our findings do not support a role of C. trachomatis, U. urealyticum, M. hominis, HCMV, or AAV infections in miscarriages during the first trimester of pregnancy. However, further investigation should be made to determine a possible involvement of HPVs in the development of genetic abnormalities of the fetus and in miscarriages.     

The role of parental translocations in cases of repeated miscarriages

In families in which spontaneous miscarriages are very frequent, a systematic search for parental translocations must be made. An examination of the karyotype appears to be justified in patients with three or more miscarriages (probabilily of detecting a translocation equal to or greater than 1 percent). The results of cytogenetic analysis will indicate in many cases the prognosis for subsequent pregnancies and will to a large extent determine the procedure to be followed.     

Genomics' role in understanding the pathogenesis of endometriosis

Endometriosis is a benign, estrogen-dependent disorder that has multifactorial components presumed in its pathogenesis. The molecular mechanisms underlying endometrial tissue attachment to the peritoneal surface or metaplasia of the mesothelium, and subsequent invasion and establishment of a blood supply and survival of the endometriotic implants, are not well understood. Recent advances in molecular biology and genomics suggest an intrinsic abnormality in the eutopic endometrium of women with endometriosis that predisposes to these processes. These are discussed herein.     

The role of iron in the pathogenesis of endometriosis

Background.?Endometriosis may cause symptoms including chronic pelvic pain and infertility, and increases susceptibility to the development of ovarian cancer. Genomic studies have started to delineate the wide array of mediators involved in the development of endometriosis. Understanding the mechanisms of endometriosis development and elucidating its pathogenesis and pathophysiology are intrinsic to prevention and the search for effective therapies.

Method of study.?The present article reviews the English language literature for biological, pathogenetic and pathophysiological studies on endometriosis. Several recent genomic studies are discussed in the context of endometriosis biology.

Results.?Severe hemolysis occurring during the development of endometriosis results in high levels of free heme and iron. These compounds oxidatively modify lipids and proteins, leading to cell and DNA damage, and subsequently fibrosis development. Recent studies based on genome-wide expression analysis technology have noted specific expression of heme/iron-dependent mediators in endometriosis. The heme/iron-dependent signaling pathway of endometriosis, which is providing new insights into the regulation of inflammation, detoxification and survival, is discussed.

Conclusion.?Several important endometriosis-specific genes overlap with those known to be regulated by iron. Other genes are involved in oxidative stress. Iron has a significant impact on endometriotic-cell gene expression. This review summarizes recent advances in the heme/iron-mediated signaling and its target genes, outlines the potential challenges to understanding of the pathogenesis and pathophysiology of endometriosis, and proposes a possible novel model.     

VEGF在子宫内膜异位症发病机制中的作用

目的:探讨血管内皮生长因子(Vascular endothelial growth factor,VEGF)在子宫内膜异位症(Endometriosis,EMs)组织中的表达及其在EMs发生发展中的作用。方法:采用ELISA法检测30例EMs患者(研究组)和16例子宫肌瘤患者(对照组)血清和腹腔液中的VEGF水平,免疫组化和RT-PCR检测并比较VEGF蛋白、VEGF mRNA在EMs异位内膜、在位内膜和对照组正常内膜的表达及其相关性。结果:EMs患者腹腔液、异位内膜、在位内膜VEGF蛋白及mRNA均明显高于对照组(P<0.05),但与EMs临床分期无关。EMs患者血清VEGF与对照组相比无明显的差异(P>0.05)。EMs患者异位内膜和在位内膜的微血管密度(MVD)明显高于对照组内膜(P<0.05)。结论:VEGF在EMs患者的高表达,说明其通过促血管生成在该病发生发展中起着重要作用。     

Chromosomal anomalies in first-trimester miscarriages

BACKGROUND. It is well known that a large proportion of first-trimester spontaneous abortions is caused by chromosomal disorders. The present study represents a unique material and the success rate of the karyotyping was high. METHODS. Chromosomal analysis from chorionic villus sampling of 259 of 304 consecutive first-trimester miscarriages in the Uppsala County, Sweden is presented. RESULTS AND CONCLUSIONS. An abnormal karyotype was found in 61% of the cases. Autosomal trisomies were most frequently detected (in 37% of the karyotyped samples), followed by polyploidies (9%) and monosomy X (6%). Cases with an extra sex chromosome constituted approximately 5% of the karyotyped abortions, with a remarkable high frequency of 47,XXY (3.4%), that is approximately 40 times greater the prevalence of Klinefelter syndrome among live birth. Similar to autosomal chromosome abnormalities, present finding indicates that the majority of sex chromosome abnormalities do not survive to term. Autosomal trisomies and an extra X-chromosome in males (47,XXY) were associated with an advanced maternal age, whereas monosomy X as well as polyploidy changes seems to be inversely related to the age of the mother. The single most common aberration was trisomy 16, which was found in 14% of the chromosomally abnormal abortions.     

米非司酮配伍米索前列醇抗早孕蜕膜与绒毛细胞凋亡及其调控基 …

目的 探讨细胞凋亡及其调控基因Ｂ－细胞淋巴瘤／白血病－２（ｂｃｌ－２）,ｂｃｌ－２相关Ｘ蛋白（ｂａｘ）基因的表达与药物终止早孕的关系,方法 对随机采用米非司酮负吸收（１５例米非司酮组）米非司酮并米索前列醇（米索）（１４例,米非司酮米索组）,负压吸收（１５例,对照组）终止早孕经碘化丙锭染色的蜕膜与绒毛组织,应用流式细胞定性定量分析技术进行ＤＮＡ分析,采用免疫荧光标记对Ｂｃｌ－２,ｂａｘ基因蛋白进行分     

The frequency of miscarriages in the users of oral contraception

Overuse of oral contraceptives (OC) is currently raising medical problems due to this medication's side effects on the immune system of future mothers. The high rate of miscarriages recorded among OC users is only one facet of the immune disorders often found in these women. This article emphasizes the precautions that should be taken with such medications in teen-agers. If the pregnancy is accompanied with an immune dysfunction exposing the future mother to subsequent infections, this will occur in patients weakened by OC, and will result in troublesome immune disorders. Therefore the notion of OC and miscarriage in pregnant women must lead to consider these as high at risk patients.     

The role of prostaglandins in the immunosuppressive effects of supernatants from adherent cells of murine decidual tissue

Supernatants from short-term cultures of murine decidual tissue (DS) were assessed for their regulatory effects on T cell lymphoproliferation and cytotoxic T lymphocyte (CTL) activity. DS non-specifically suppressed antigen- and mitogen-induced lymphoproliferation, spontaneous thymocyte proliferation, the mixed lymphocyte reaction (MLR) and CTL generation, but had no effect on CTL lytic activity. The immunosuppressive activity was lost after dialysis (14 kDa cut off). Supernatants from indomethacin-treated decidual tissue cultures (indomethacin-DS) lacked suppressive activity in the MLR, mitogen and thymocyte proliferation assays. Indomethacin-DS also showed markedly reduced or no suppressive effects on CTL generation. These findings suggest that prostaglandin production by the decidual component of the placenta could play a role in materno-fetal cellular interactions by regulating T cell lymphoproliferative responses and CTL generation.     

A possible ambivalent role for relaxin in human myometrial and decidual cells in vitro

Purpose  

Based on the reported tocolytic action of the hormone relaxin (RLX) in rodents, locally produced in reproductive tissues and the corpus luteum in mammals, the present study aimed to evaluate the influence of RLX on contraction-mediating cyclooxygenases-1 and -2 (COX) and the contractile prostaglandin PGE₂ in human myometrial and decidual cells. Primary cultured cells were obtained from uteri and placentas of term and preterm women undergoing elective caesarean section.     

Ia antigen-bearing decidual cells and macrophages in cultures of mouse decidual tissue

The ontogeny of Ia antigen expression on cells within the decidua basalis of the placenta and on decidual cells differentiating in vitro was investigated in the mouse. The results indicate that Ia antigen expression is temporarily restricted and can be detected in short-term cultures of decidual tissue only during the final third of gestation. The Ia antigen positive cells, which are non-phagocytic, non-specific esterase negative and lack Fc receptors, appear to be true decidual cells on the basis of their fine structural characteristics. In contrast, morphologically identical dendritic decidual cells arising from differentiation in vitro of endometrial cells do not express Ia antigens. A population of small rounded cells was also present in cultures of both decidual tissue and in vitro decidualized endometrial cells. These rounded cells possess the macrophage-like properties of Fc receptors, non-specific esterase and phagocytic activity. The possible function of these cell populations within the decidual tissue is discussed.