Journal of reproductive health and medicine最新文献

The impact of elevated serum progesterone levels on pregnancy and live birth during in vitro fertilization (IVF) remains unclear. Our objective was to investigate whether elevated serum progesterone on the day of human chorionic gonadotropin (HCG) administration is associated with lower pregnancy and live birth rates. This mini review provides a synopsis of the literature in addition to some of our own data. On the whole pregnancy and live birth rates decrease with increasing progesterone on the day of HCG administration even after adjusting for confounders. The findings from the majority of manuscripts investigating this question appear to be in agreement.

Poor uterine receptivity leads to implantation defects or failure. Identification of uterine molecules crucial to uterine receptivity and/or embryo implantation provides the opportunity to design a diagnostic screening toolkit for uterine receptivity or targeted drug discovery for treating implantation-based infertility. In this regard, gene-profiling studies performed in humans and rodents have identified numerous genes involved in the transcriptional regulation of uterine receptivity and embryo implantation. In this article, we compared available uterine microarray datasets collected during the time of uterine receptivity and implantation in humans, mice and hamsters to uncover conserved gene sets. We also compared the transcriptome signature of women with unexplained infertility (UIF) and recurrent implantation failure (RIF) to gain insight into genes potentially dysregulated during endometrial receptivity or embryo implantation. Among numerous differentially expressed genes, few were revealed that might have molecular diagnostic screening potential for identifying the uterine receptive state during the time of implantation. Finally, functional annotation of gene sets uncovered altered uterine apoptosis or cell adhesion pathways in women with UIF and RIF, respectively. These conserved or divergent gene sets provide insights into the uterine receptive state for supporting blastocyst implantation.

Endometrial carcinomas (ECs) are the most common gynecologic malignancies, exceeding the incidence of ovarian and cervical cancers in elderly women (post-menopausal) in Western countries. Evidence suggests that it is a luteinizing hormone (LH) dependent disease. ECs overexpress LH/human chorionic gonadotropin (hCG) receptors as compared with pre and post-menopausal endometria. Activation of the LH/hCG receptors in primary and immortalized EC cells results in an increased cell proliferation and invasion, which are mediated by cyclic AMP(cAMP)/protein kinase A (PKA) signaling, require the presence of LH/hCG receptors, activation of β₁ integrin receptors and an increase in the secretion of metalloproteinase-2 (MMP-2) in its active form. In addition to the endometrium, LH actions in the ovaries and adrenal glands results in an increased secretion of androgens, which are aromatized into estrogens in the adipose and EC tissues. LH also has direct effects in the pancreas, which results in an increase in insulin secretion, which in turn can also stimulate ovarian stromal cell proliferation, luteinization, androgens secretion and aromatization in adipose and EC tissues. LH is further elevated in post-menopausal women who develop EC as compared with post-menopausal women who do not develop the disease. These findings support complex network of LH actions that promote EC development in elderly women.

Extravillous trophoblasts (EVTs) invade the decidual stroma (interstitial trophoblast) and thereby attach the placenta to the uterus. They also invade toward spiral arteries (endovascular trophoblast) for the establishment of the uteroplacental blood flow. The latter does not start before the end of the first trimester of pregnancy. A new type of extravillous trophoblast invading into uterine glands (endoglandular trophoblast) has been described recently opening uterine glands toward the intervillous space of the placenta to enable histiotrophic nutrition. This review gives an overview about the different subtypes of EVTs and presents novel peculiarities in the field of EVT invasion. EVTs invade more structures in the maternal decidua than previously assumed. Especially a proper invasion of uterine glands by endoglandular trophoblasts may have more impact on the outcome of pregnancy than assumed so far.

Human embryonic stem cells (hESCs), owing to their potential promise to develop into any somatic cell type, have radicalized biotechnology research and application in clinical medicine. The source of hESCs has traditionally been viable cells retrieved from preimplantation stage embryos grown in culture in IVF-ET clinics. The present article deals with various crucial moral, ethical and governance issues pertaining to biomedical research and clinical application using hESCs. We have also addressed the progress of clinical translation of hESC biotechnology from its inception to the present scenario and its consequent societal impact today. Additionally, various safety factors which are to be instituted before clinical applications of hESC products to patients have been discussed. Finally, the ethical progress about the dilemma between treating the hESC as potential ‘human being’ and as an instrument to alleviate the sufferings of human race has been examined from various scientific and epistemic perspectives.

A major goal of regenerative medicine is to devise strategies to restore structure and function of damaged or lost organs/tissues. Stem cell therapy has emerged as one of the most promising tools in regenerative medicine. The ability to self-renew and differentiate into multiple cell types positions stem cells as wonder drugs or cellular drugs of the future. Recent accomplishments in transforming terminally differentiated cells to stem cells by reprogramming have widened the scope of opportunities for regenerative medicine. On the other hand, stem cells are believed to have a causal role in the pathogenesis of some diseases such as cancers. These wide-ranging clinical implications have driven researchers to search different tissues and organs for the presence of stem cells and characterize them further for their differentiation potential. The endometrium or the inner lining of the uterus has also been explored for the presence of stem cells. Endometrial stem cells (ESCs) have gained importance, not only because of their multi-potent nature but also due to the ease of their availability through a natural event i.e. menstruation. The first evidence for the presence of stem cells in human endometrium arrived in 2004. Since then, ESCs displaying different molecular phenotypes have been identified in humans. ESCs have been shown to differentiate into the cells of different lineages. Further, ESCs have been investigated for their potential role in some uterine pathologies. This review provides a bird's eye-view of our current understanding pertaining to the role of stem cells in the pathogenesis of endometriosis.

Foetal immunotolerance is one of the major challenges of pregnancy which is surmounted in part by both, the foetus and the mother. This review highlights the role of two decidual proteins, galectin-1 and glycodelin A (GdA) in achieving localized immunosuppressive state in the uterus. The two proteins have similar effects on T cells, inhibiting their proliferation, inducing apoptosis, inhibiting IL-2 production, but, helping in the expansion of Treg cells. They also induce tolerogenicity in dendritic cells, B cells and monocytes. In addition, GdA suppresses the lytic activity of cytotoxic T cells and induces apoptosis in monocytes as well as NK cells. Overall, galectin-1 and GdA inhibit the proliferation of immune cells, decrease their cytotoxicity and induce an anti-inflammatory cytokine environment. Thus leading to modulation of the immune response at the feto-maternal interface aiding in the maintenance of pregnancy to full term. The two proteins, other than having overlapping functions share similarity only in being lectins. Both are structurally different; galectin-1 has a non-glycosylated β-sandwich while GdA has a glycosylated β-barrel. Evolutionarily, GdA is found only in higher primates and appears to be functionally restricted to pregnancy, whereas galectin-1 is found in most mammals and has a role in immunomodulation at almost all immune privileged sites.