Implantation failures in women with infertility associated endometriosis

Abstract

Endometriosis is currently considered as one of the most common diseases associated with infertility. A controversial issue is whether endometriosis per se exerts a detrimental effect on IVF outcomes. Failure of implantation due to endometriosis-associated infertility is a contradictory and widely discussed burden nowadays. The purpose of the study is to assess the quality of embryos and implantation rate in women with infertility associated with endometriosis. The study included infertile reproductive aged women, between 26 and 40 years who underwent IVF and ICSI procedures. The patients were divided into two groups: group I (n?=?70) involved 70 patients with recurrent unilateral endometriomas, II control group (n?=?50) with tubal factor infertility. The quality of the retrieved embryos was assessed according to the generally accepted classification of Gardner, indicating the rate of implantation in each group. Embryo transfer was performed in case of high quality embryos. Assessing the ovarian reserve indicators, in the group I patients with recurrent unilateral endometriomas the serum level of AMH was significantly lower (2.1?±?1.75 vs. 3.2?±?1.4, p?<?.005), as well as the number of retrieved oocytes (8.1?±?3.9 and 10.1?±?6.8, p?<?.005). The analysis of the results demonstrated that the duration of stimulation in the group patients with recurrent unilateral endometriomas was significantly higher in comparison with the group II (12.2?±?1.8 and 10.2?±?1.6 days, p?<?.001). Nevertheless, the number of good quality embryos retrieved was comparable in both groups (2.2?±?1.5 and 2.8?±?1.8). In the group I patients with recurrent unilateral endometriomas, there was a statistically significant decrease of implantation rate (17.1% vs. 24% p?<?.005). The results of the study revealed no statistical difference in embryo quality in the study cohort. However, it is important to note that a statistically significant difference in implantation rate in the group of endometriosis-associated infertility compared was obtained 1.5 times lower than in the control group (15.8% vs. 24.0% p?<?.005). The achieved results demonstrated an adverse IVF outcome in infertile women with recurrent endometrioma compared to the control group.     

The underdeveloped innate immunity in embryonic stem cells: The molecular basis and biological perspectives from early embryogenesis

Embryonic stem cells (ESCs) have been intensively studied as a promising cell source for regenerative medicine. The rapid advancements in the field have not only proven the feasibility of ESC‐based cell therapy, but also led to a better understanding of pluripotent stem cells (PSCs) as a unique cell population at an early stage of embryogenesis. Recent studies have revealed that both human and mouse ESCs have attenuated innate immune responses to infectious agents and inflammatory cytokines. These findings raise interesting questions about the rationale for ESCs, the PSCs experimentally derived from preimplantation stage embryos, to not have an innate defense mechanism that has been adapted so well in somatic cells. All somatic cells have innate immune systems that can be activated by pathogen‐associated molecular patterns (PAMPs) or cellular damage‐associated molecular patterns (DAMPs), leading to production of cytokines. The underdeveloped innate immunity represents a unique property of PSCs that may have important implications. This review discusses the immunological properties of PSCs, the molecular basis underlying their diminished innate immune responses, and the hypothesis that the attenuated innate immune responses could be an adaptive mechanism that allows PSCs to avoid cytotoxicity associated with inflammation and immune responses during early embryogenesis.     

丹参晚期胚胎富集蛋白基因的克隆及表达模式分析

目的克隆丹参晚期胚胎富集蛋白(late embryogenesis abundant protein,LEA)基因,并进行生物信息学和表达模式分析。方法对丹参转录组数据库进行BLAST同源性比对,发现一条新的与LEA基因家族同源性较高的序列,命名为Sm LEA2,Gen Bank登录号为HQ676610。进一步利用PCR和RT-PCR技术从丹参g DNA以及c DNA水平克隆得到了Sm LEA2基因全长。采用软件分析蛋白质结构性质和系统进化关系。利用实时荧光定量PCR的方法对不同部位、不同发育时期以及不同处理丹参的Sm LEA2表达量进行检测。结果获得Sm LEA2 g DNA长1 961 bp,由1个外显子和1个内含子组成,并且内含子位于ATG的上游;开放阅读框长为960 bp,共编码319个氨基酸。生物信息学分析显示,Sm LEA2是存在于细胞质中的亲水蛋白,无跨膜结构域和信号肽,其相对分子质量为35 340,等电点为4.77。该基因在丹参的根、茎、叶中均有表达,并且在茎中的表达量最高。随着花的成熟和种子的发育,该基因表达量逐渐升高,并且该基因的表达受茉莉酸甲酯(Me JA)以及脱落酸(ABA)的诱导作用影响。结论克隆得到的丹参Sm LEA2可能参与种子发育过程,并在丹参防御反应中发挥作用。     

Tryptophan-independent auxin biosynthesis contributes to early embryogenesis in Arabidopsis

The phytohormone auxin regulates nearly all aspects of plant growth and development. Tremendous achievements have been made in elucidating the tryptophan (Trp)-dependent auxin biosynthetic pathway; however, the genetic evidence, key components, and functions of the Trp-independent pathway remain elusive. Here we report that the Arabidopsis indole synthase mutant is defective in the long-anticipated Trp-independent auxin biosynthetic pathway and that auxin synthesized through this spatially and temporally regulated pathway contributes significantly to the establishment of the apical–basal axis, which profoundly affects the early embryogenesis in Arabidopsis. These discoveries pave an avenue for elucidating the Trp-independent auxin biosynthetic pathway and its functions in regulating plant growth and development.The phytohormone auxin plays critical roles in almost every aspect of plant development including embryogenesis, architecture formation, and tropic growth. One of the most fascinating topics in plant biology is how auxin can have so many diverse and context-specific functions (1). Dynamic auxin gradients, which are regulated mainly by local auxin synthesis, catabolism, conjugation, and polar auxin transport, are essential for integration of various environmental and endogenous signals (2, 3). Auxin perception and signaling systems are responsible for a read-out of the auxin gradients (1).Local auxin biosynthesis is important for leaf development, shade avoidance, root-specific ethylene sensitivity, vascular patterning, flower patterning, and embryogenesis (4). Indole-3-acetic acid (IAA), the naturally occurring principal auxin in plants, is biosynthesized from tryptophan (Trp) through four proposed routes according to their key intermediates, namely indole-3-acetaldoxime (IAOx), indole-3-pyruvic acid (IPyA), indole-3-acetamide (IAM), and tryptamine (TAM) (5). The TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS (TAA)/YUCCA (YUC) linear pathway has been considered as a predominant Trp-dependent auxin biosynthetic pathway (4, 6–8). However, labeling studies and analyses of Trp auxotrophic mutants have long predicted the existence of a Trp-independent IAA biosynthetic pathway (9–13). When the Arabidopsis and maize seedlings were fed with isotope-labeled precursor, IAA was more enriched than Trp, and the incorporation of label into IAA from Trp is low, suggesting that IAA can be produced de novo without Trp as an intermediate (11, 12). The Trp biosynthetic mutant trp1, defective in phosphoribosylanthranilate transferase (PAT), and indole-3-glycerol phosphate synthase (IGS) antisense plants are deficient in steps earlier than indole-3-glycerol phosphate (IGP) formation and display decreased levels of both IAA and Trp (10, 14). However, the trp3 and trp2 mutants, defective in tryptophan synthase α (TSA) and tryptophan synthase β (TSB) subunits, respectively, accumulate higher levels of IAA than the wild type despite containing lower Trp levels (10, 11, 15, 16). These data strongly suggested the existence of the Trp-independent IAA biosynthetic pathway that might branch from IGP and/or indole (10). Further studies suggested that a cytosol-localized indole synthase (INS) may be involved in the Trp-independent biosynthesis of indole-containing metabolite (17). However, the molecular basis, biological functions, and spatiotemporal regulation of the Trp-independent IAA biosynthetic pathway have remained a mystery.In higher eukaryotes, embryogenesis initiates the generation of the species-specific body plan. During embryogenesis, a single-celled zygote develops into a functional multicellular organism with cells adopting specific fates according to their relative positions. In higher plants, essential architecture features, such as body axes and major tissue layers, are established in embryogenesis, and auxin plays a vital role in apical-basal patterning and embryo axis formation (18, 19). Local auxin biosynthesis, polar auxin transport facilitated by PIN-FORMED1/3/4/7 (PIN1/3/4/7), and auxin response coordinately regulate apical–basal pattern formation during embryogenesis (7, 20–22). The TAA and YUC families in Trp-dependent IAA biosynthesis predominantly regulate embryogenesis at or after the globular stage (7, 22). However, the auxin source for embryogenesis before the globular stage remains elusive. In this study, we provide, to our knowledge, the first genetic and biochemical evidence that the cytosol-localized INS is a key component in the long predicted Trp-independent auxin biosynthetic pathway and is critical for apical–basal pattern formation during early embryogenesis in Arabidopsis.     

Pontin is essential for murine hematopoietic stem cell survival

Pontin is a highly conserved DNA helicase/ATPase which is a component of several macromolecular complexes with functions that include DNA repair, telomere maintenance and tumor suppression. While Pontin is known to be essential in yeast, fruit flies and frogs, its physiological role in mammalian organisms remains to be determined. We here find that Pontin is highly expressed in embryonic stem cells and hematopoietic tissues. Through germline inactivation of Ruvbl1, the gene encoding Pontin, we found it to be essential for early embryogenesis, as Ruvbl1 null embryos could not be recovered beyond the blastocyst stage where proliferation of the pluripotent inner cell mass was impaired. Conditional ablation of Ruvbl1 in hematopoietic tissues led to bone marrow failure. Competitive repopulation experiments showed that this included the loss of hematopoietic stem cells through apopotosis. Pontin is, therefore, essential for the function of both embryonic pluripotent cells and adult hematopoietic stem cells.     

Reverse engineering the mechanical and molecular pathways in stem cell morphogenesis

The formation of relevant biological structures poses a challenge for regenerative medicine. During embryogenesis, embryonic cells differentiate into somatic tissues and undergo morphogenesis to produce three‐dimensional organs. Using stem cells, we can recapitulate this process and create biological constructs for therapeutic transplantation. However, imperfect imitation of nature sometimes results in in vitro artifacts that fail to recapitulate the function of native organs. It has been hypothesized that developing cells may self‐organize into tissue‐specific structures given a correct in vitro environment. This proposition is supported by the generation of neo‐organoids from stem cells. We suggest that morphogenesis may be reverse engineered to uncover its interacting mechanical pathway and molecular circuitry. By harnessing the latent architecture of stem cells, novel tissue‐engineering strategies may be conceptualized for generating self‐organizing transplants. Copyright © 2013 John Wiley & Sons, Ltd.