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Paracrine support of ovarian stimulationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Assisted reproductive technology has evolved on the back of blunderbuss ovarian stimulation regimes designed to maximize the number of oocytes recoverable for treatment purposes. However, oocyte ‘quality’ is finely programmed by local paracrine and autocrine signalling events during folliculogenesis and can be adversely affected by inappropriate gonadotrophic stimulation. This brief review traces the full follicular lifespan—from initiation to ovulation—to identify gonadotrophin-responsive checkpoints likely to impact oocyte quality. It is argued that these might be targeted during controlled ovaria...
Source: Molecular Human Reproduction - November 12, 2009 Category: Molecular Biology Authors: Hillier, S. G. Tags: New Research Horizon Reviews Source Type: journals

Genetic and gene expression analyses of the polycystic ovary syndrome candidate gene fibrillin-3 and other fibrillin family members in human ovariesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Several studies have demonstrated an association between polycystic ovary syndrome (PCOS) and the dinucleotide repeat microsatellite marker D19S884, which is located in intron 55 of the fibrillin-3 (FBN3) gene. Fibrillins, including FBN1 and 2, interact with latent transforming growth factor (TGF)-β-binding proteins (LTBP) and thereby control the bioactivity of TGFβs. TGFβs stimulate fibroblast replication and collagen production. The PCOS ovarian phenotype includes increased stromal collagen and expansion of the ovarian cortex, features feasibly influenced by abnormal fibrillin expression. To examine a poss...
Source: Molecular Human Reproduction - November 12, 2009 Category: Molecular Biology Authors: Prodoehl, M. J., Hatzirodos, N., Irving-Rodgers, H. F., Zhao, Z. Z., Painter, J. N., Hickey, T. E., Gibson, M. A., Rainey, W. E., Carr, B. R., Mason, H. D., Norman, R. J., Montgomery, G. W., Rodgers, R. J. Tags: Original Article Source Type: journals

Control of ovulation in mice by progesterone receptor-regulated gene networksEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The mid-cycle surge of luteinizing hormone (LH) induces ovulation, a process during which a fertilizable oocyte is released from a mature ovarian follicle. Although ovulation is a physiologically well-characterized event, the underlying molecular pathways remain poorly understood. Progesterone receptor (PGR), which mediates the biological effects of the steroid hormone progesterone, has emerged as a key regulator of ovulation in mice. The development of a progesterone-receptor-null (Pgr-null) mouse model confirmed a critical role of this hormone in ovulation because in these mutant mice, mature pre-ovulatory follicles fail...
Source: Molecular Human Reproduction - November 12, 2009 Category: Molecular Biology Authors: Kim, J., Bagchi, I. C., Bagchi, M. K. Tags: New Research Horizon Reviews Source Type: journals

Oogenesis and cell death in human prenatal ovaries: what are the criteria for oocyte selection?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Prenatal oogenesis produces hundreds of thousands of oocytes, most of which are discarded through apoptosis before birth. Despite this large-scale selection, the survivors do not constitute a perfect population, and the factors at the cellular level that result in apoptosis or survival of any individual oocyte are largely unknown. What then are the selection criteria that determine the size and quality of the ovarian reserve in women? This review focuses on new data at the cellular level, on human prenatal oogenesis, offering clues about the importance of the timing of entry to meiotic prophase I by linking the stages and ...
Source: Molecular Human Reproduction - November 12, 2009 Category: Molecular Biology Authors: Hartshorne, G.M., Lyrakou, S., Hamoda, H., Oloto, E., Ghafari, F. Tags: New Research Horizon Reviews Source Type: journals

The primordial pool of follicles and nest breakdown in mammalian ovariesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The creation of the pool of follicles available for selection and ovulation is a multi-faceted, tightly regulated process that spans the period from embryonic development through to the first reproductive cycle of the organism. In mice, this development can occur in mere weeks, but in humans, it is sustained for years. Embryonic germ cell development involves the migration of primordial germs cells to the genital ridge, and the mitotic division of germ cell nuclei without complete cytokinesis to form a multi-nucleated syncytia, or germ cell nest. Through combined actions of germ cell apoptosis and somatic cell migration, t...
Source: Molecular Human Reproduction - November 12, 2009 Category: Molecular Biology Authors: Tingen, C., Kim, A., Woodruff, T. K. Tags: New Research Horizon Reviews Source Type: journals

Oocyte peptides as paracrine tools for ovarian stimulation and oocyte maturationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent studies report the production and isolation of a stable bioactive recombinant human bone morphogenetic protein 15 (rhBMP15) that is appropriately processed in HEK-293 cells and activates the SMAD 1/5/8 pathway in mouse granulosa cell cultures. Further, the purified rhBMP15 induces the expression of genes associated with cumulus expansion. Thanks to recent research, we have a greater understanding of the importance of the dialogue that occurs between the oocyte and the granulosa cell layer with regard to regulating folliculogenesis and the acquisition of oocyte developmental competence and maturation. BMP15 is one of...
Source: Molecular Human Reproduction - November 12, 2009 Category: Molecular Biology Authors: Mottershead, D. G., Watson, A. J. Tags: Commentary Source Type: journals

Stable expression and characterization of N-terminal tagged recombinant human bone morphogenetic protein 15Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Oocyte-derived growth factors are critically involved in multiple ovarian processes via paracrine actions. Although recombinant proteins have been applied to dissect the physiological functions of these factors, variation of activities among different protein preparations remains an issue. To further elucidate the roles of one of these growth factors, bone morphogenetic protein 15 (BMP15), in mediating oocyte-regulated molecular and cellular events and to explore its potential clinical application, we engineered the human BMP15 sequence to efficiently produce bioactive recombinant human BMP15 (rhBMP15). The proteolytic cle...
Source: Molecular Human Reproduction - November 12, 2009 Category: Molecular Biology Authors: Li, Q., Rajanahally, S., Edson, M. A., Matzuk, M. M. Tags: Original Articles Source Type: journals

The forkhead transcription factor FOXL2 is expressed in somatic cells of the human ovary prior to follicle formationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Interactions between germ cells and surrounding somatic cells are central to ovarian development as well as later function. Disruption of these interactions arising from abnormalities in either cell type can lead to premature ovarian failure (POF). The forkhead transcription factor FOXL2 is a candidate POF factor, and mutations in the FOXL2 gene are associated with syndromic and non-syndromic ovarian failure. Foxl2-deficient mice display major defects in primordial follicle activation with consequent follicle loss, and earlier roles in gonadal development and sex determination have also been suggested. However, despite its...
Source: Molecular Human Reproduction - November 12, 2009 Category: Molecular Biology Authors: Duffin, K., Bayne, R.A.L., Childs, A.J., Collins, C., Anderson, R.A. Tags: Original Articles Source Type: journals

Disruption of Tsc2 in oocytes leads to overactivation of the entire pool of primordial folliclesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we provide some genetic evidence to show that the tumor suppressor tuberous sclerosis complex 2 (Tsc2), which negatively regulates mammalian target of rapamycin complex 1 (mTORC1), functions in oocytes to maintain the dormancy of primordial follicles. In mutant mice lacking the Tsc2 gene in oocytes, the pool of primordial follicles is activated prematurely due to elevated mTORC1 activity in oocytes. This results in depletion of follicles in early adulthood, causing premature ovarian failure (POF). Our results suggest that the Tsc1–Tsc2 complex mediated suppression of mTORC1 activity is indispensable fo...
Source: Molecular Human Reproduction - November 12, 2009 Category: Molecular Biology Authors: Adhikari, D., Flohr, G., Gorre, N., Shen, Y., Yang, H., Lundin, E., Lan, Z., Gambello, M. J., Liu, K. Tags: Original Articles Source Type: journals

The ovary: from basic research to clinicEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - November 12, 2009 Category: Molecular Biology Authors: Hillier, S. G. Tags: Editorial Source Type: journals

An RNA spiking method demonstrates that 18S rRNA is regulated by progesterone in the mouse uterusEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Identifying suitable housekeeping genes for quantitative RT–PCR in the uterus is problematic, as this tissue undergoes significant structural and functional alterations during the oestrous cycle and pregnancy in response to circulating hormones. The suitability of 18S rRNA as a housekeeping gene in mouse uterus was investigated by introducing an ‘RNA spike’ standard into the reverse transcription reaction. 18S rRNA levels increased by Day 4 of pregnancy and after progesterone administration in ovariectomized mice. We conclude that 18S rRNA is not a suitable housekeeping gene for quantitative RT–PCR ...
Source: Molecular Human Reproduction - October 15, 2009 Category: Molecular Biology Authors: Craythorn, R.G., Girling, J.E., Hedger, M.P., Rogers, P.A.W., Winnall, W.R. Tags: Technical Note Source Type: journals

Regulation of soluble vascular endothelial growth factor receptor 1 secretion from human endothelial cells by tissue inhibitor of metalloproteinase 1Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, our results provide evidence that TIMP-1 increases the production of sVEGFR-1 in endothelial cells and thus may reduce VEGF bioavailability, leading to reduced blood vessel growth in the ovary. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - October 15, 2009 Category: Molecular Biology Authors: Bruegmann, E., Gruemmer, R., Neulen, J., Motejlek, K. Tags: Original Research Source Type: journals

Evaluation of genome coverage and fidelity of multiple displacement amplification from single cells by SNP arrayEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The scarce amount of DNA contained in a singe cell is a limiting factor for clinical application of preimplantation genetic diagnosis mainly due to the risk of misdiagnosis caused by allele dropout and the difficulty in obtaining copy number variations in all 23 pairs of chromosomes. Multiple displacement amplification (MDA) has been reported to generate large quantity of products from small amount of templates. Here, we evaluated the fidelity of whole-genome amplification MDA from single or a few cells and determined the accuracy of chromosome copy number assessment on these MDA products using an Affymetrix 10K 2.0 SNP Ma...
Source: Molecular Human Reproduction - October 15, 2009 Category: Molecular Biology Authors: Ling, J., Zhuang, G., Tazon-Vega, B., Zhang, C., Cao, B., Rosenwaks, Z., Xu, K. Tags: Original Research Source Type: journals

Mutations in the protamine locus: association with spermatogenic failure?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The protamine locus consists of a 28.5 kb region with a linear array of the protamine (PRM)1, PRM2, PRM3 and transition nuclear protein (TNP)2 genes. Several studies indicate an abnormal expression pattern of protamine genes associated with male infertility, although the molecular mechanism underlying this observation is unclear. Here, we determined the spectrum of DNA variants present in all four genes in men with unexplained infertility compared with an ancestry-matched fertile/normospermic population. A total of 160 control individuals and at least 125 infertile men with either idiopathic azoospermia or oligozoospermia ...
Source: Molecular Human Reproduction - October 15, 2009 Category: Molecular Biology Authors: Imken, L., Rouba, H., El Houate, B., Louanjli, N., Barakat, A., Chafik, A., McElreavey, K. Tags: Original Research Source Type: journals

Metastasis associated lung adenocarcinoma transcript 1 is up-regulated in placenta previa increta/percreta and strongly associated with trophoblast-like cell invasion in vitroEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, annealing control primer–polymerase chain reaction (ACP–PCR) was used to identify differentially expressed genes, which may impair placentation resulting in placenta previa I/P. Placental tissues from I/P and non-increta/percreta (non-I/P) sites were concomitantly collected from patients undergoing Cesarean hysterectomy. After ACP–PCR experiments (three patients), the differentially expressed bands, consistently showing up- or down-regulated trends between each of the I/P and non-I/P tissue pairs, were cloned and sequenced. Human non-protein coding metastasis associated lung adenocarcinoma ...
Source: Molecular Human Reproduction - October 15, 2009 Category: Molecular Biology Authors: Tseng, J.-J., Hsieh, Y.-T., Hsu, S.-L., Chou, M.-M. Tags: Original Research Source Type: journals

Leukocytes are primed in peripheral blood for activation during term and preterm labourEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We hypothesized that the priming and activation of maternal leukocytes in peripheral blood is a key component of parturition, and that inappropriate preterm priming of leukocytes might initiate preterm labour and delivery. The purpose of this study was to characterize peripheral blood leukocyte activation during human term and preterm labour. We obtained blood samples from pregnant women at term and preterm, both in labour and not in labour. Leukocytes were characterized according to cell subtype and cell surface marker expression. Additionally, we quantified leukocyte cytokine mRNA production, migratory ability and reacti...
Source: Molecular Human Reproduction - October 15, 2009 Category: Molecular Biology Authors: Yuan, M., Jordan, F., McInnes, I.B., Harnett, M.M., Norman, J.E. Tags: Original Research Source Type: journals

Recent progress in luteinizing hormone/human chorionic gonadotrophin hormone researchEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The role of luteinizing hormone (LH) and human chorionic gonadotrophin hormone (hCG) in the regulation of normal reproductive functions in males and females is quite well established. Besides the use of hCG in the development of diagnostic immunoassays, it has been successfully used in the induction of final follicular maturation and ovulation in the assisted reproductive technologies. The basic and clinical research on the nongonadal actions of LH/hCG in the recent years has extended the potential of using these hormones in several clinical indications. Hereby we will analyze the advances in the LH/hCG research (briefly e...
Source: Molecular Human Reproduction - October 15, 2009 Category: Molecular Biology Authors: Rahman, N. A., Rao, C.V. Tags: New Research Horizon Reviews Source Type: journals

Dienogest, a synthetic progestin, inhibits the proliferation of immortalized human endometrial epithelial cells with suppression of cyclin D1 gene expressionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we examined the direct effects of dienogest on the proliferation of human endometrial epithelial cells using an immortalized cell line. 5-Bromo-2'-deoxyuridine incorporation into the cells was inhibited by dienogest and by progesterone (P4) in dose-dependent fashion at concentrations of 10–8 mol/l or higher. To identify the target genes of dienogest and P4, we screened the expression of 84 genes related to cell cycle regulation by real-time polymerase chain reaction after 6 h of treatment at a concentration of 10–7 mol/l. Results showed that only cyclin D1 expression was significantly down-regula...
Source: Molecular Human Reproduction - September 14, 2009 Category: Molecular Biology Authors: Shimizu, Y., Takeuchi, T., Mita, S., Mizuguchi, K., Kiyono, T., Inoue, M., Kyo, S. Tags: Articles Source Type: journals

Peroxisome-proliferator activator receptor-gamma activation decreases attachment of endometrial cells to peritoneal mesothelial cells in an in vitro model of the early endometriotic lesionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, CTZ significantly decreased EM42 attachment to LP9 cells and HA in an in vitro model of the early endometriotic lesion. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - September 14, 2009 Category: Molecular Biology Authors: Kavoussi, S.K., Witz, C.A., Binkley, P.A., Nair, A.S., Lebovic, D.I. Tags: Articles Source Type: journals

Differential actions of estrogen and SERMs in regulation of the actin cytoskeleton of endometrial cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Estrogen and selective estrogen receptor modulators (SERMs) differentially impact endometrial cell function, however, the biological basis of these differences is not established. Deregulated cell adhesion to the extracellular matrix, cell movement and invasion are related to endometrial disorders, such as endometriosis or endometrial cancer. Remodeling of the actin cytoskeleton is required to achieve cell adhesion and movement. Estrogen receptor (ER) regulates actin and cell membrane remodeling through extra-nuclear signaling cascades. In this article, we show that administration of 17β-estradiol (E2) and tamoxifen (...
Source: Molecular Human Reproduction - September 14, 2009 Category: Molecular Biology Authors: Flamini, M.I., Sanchez, A.M., Goglia, L., Tosi, V., Genazzani, A.R., Simoncini, T. Tags: Articles Source Type: journals

Induction of endometrial epithelial cell invasion and c-fms expression by transforming growth factor betaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Transforming growth factor beta 1 (TGF-β1) levels are increased in the peritoneal fluid of endometriosis patients, and endometrial cells express TGF-β signaling components; however, little is known regarding the role of TGF-β in endometriosis. Our objective was to examine the effects of TGF-β1 on (i) the expression of macrophage colony-stimulating factor receptor encoded by the c-fms gene, (ii) transmesothelial invasiveness of endometrial cells, (iii) cellular proliferation and (iv) attachment to peritoneal mesothelial cells (PMCs). Effects of TGF-β1 on c-fms mRNA expression were determined by real...
Source: Molecular Human Reproduction - September 14, 2009 Category: Molecular Biology Authors: Liu, Y.-g., Tekmal, R. R., Binkley, P. A., Nair, H. B., Schenken, R. S., Kirma, N. B. Tags: Articles Source Type: journals

Endometriotic stromal cells lose the ability to regulate cell-survival signaling in endometrial epithelial cells in vitroEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In normal endometrium, stromal factors regulate the growth of epithelial cells. However, epithelial cells in endometriotic lesions display increased proliferation and decreased apoptosis. This work tested the hypothesis that in endometriosis stromal cells lose the ability to regulate survival signaling and cell growth in epithelial cells. Primary normal, endometriotic eutopic and ectopic epithelial cells were cultured in the presence of medium conditioned by normal, eutopic and ectopic endometriotic endometrial stromal cells. Endometriotic epithelial cells showed higher Survivin expression than normal epithelial cells. Con...
Source: Molecular Human Reproduction - September 14, 2009 Category: Molecular Biology Authors: Zhang, H., Li, M., Zheng, X., Sun, Y., Wen, Z., Zhao, X. Tags: Articles Source Type: journals

Connexin expression pattern in the endometrium of baboons is influenced by hormonal changes and the presence of endometriotic lesionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Experimentally induced endometriosis in baboons serves as an elegant model to discriminate between endometrial genes which are primarily associated with normal endometrial function and those that are changed by the presence of endometriotic lesions. Since connexin genes are characteristic of the hormonally regulated differentiation of the endometrium, we have examined connexin expression in baboon endometrium to delineate if they are altered in response to the presence of endometriotic lesions. Connexin expression in the endometrium of cycling baboons is similar to that of the human endometrium with Connexin(Cx)43 being pr...
Source: Molecular Human Reproduction - September 14, 2009 Category: Molecular Biology Authors: Winterhager, E., Grummer, R., Mavrogianis, P.A., Jones, C.J.P., Hastings, J.M., Fazleabas, A.T. Tags: Articles Source Type: journals

Progestins inhibit expression of MMPs and of angiogenic factors in human ectopic endometrial lesions in a mouse modelEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Progestins are successfully used in the treatment of endometriosis; however, the exact mechanisms of their action are still unsolved. We here focused on the effect of different progestins on parameters of extracellular matrix degradation and angiogenesis involved in the establishment and maintenance of ectopic endometrial lesions. Human endometrium was intraperitoneally transplanted into nude mice. After 7 and 28 days of treatment with progesterone, dydrogesterone, or its metabolite dihydrodydrogesterone, respectively, ectopic lesions were evaluated for proliferation and apoptosis. Expression of estrogen receptor , progest...
Source: Molecular Human Reproduction - September 14, 2009 Category: Molecular Biology Authors: Monckedieck, V., Sannecke, C., Husen, B., Kumbartski, M., Kimmig, R., Totsch, M., Winterhager, E., Grummer, R. Tags: Articles Source Type: journals

MicroRNA expression profiling of eutopic secretory endometrium in women with versus without endometriosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report distinct miRNA expression profiles in the ESE of women with versus without endometriosis in a subset of samples previously used in global gene expression analysis. Specifically, the miR-9 and miR-34 miRNA families evidenced dysregulation. Integration of the miRNA and gene expression profiles provides unique insights into the molecular basis of this enigmatic disorder and, possibly, the regulation of the proliferative phenotype during the early secretory phase of the menstrual cycle in affected women. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - September 14, 2009 Category: Molecular Biology Authors: Burney, R.O., Hamilton, A.E., Aghajanova, L., Vo, K.C., Nezhat, C.N., Lessey, B.A., Giudice, L.C. Tags: Articles Source Type: journals

Reassessing the evidence for the link between dioxin and endometriosis: from molecular biology to clinical epidemiologyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, it seems that there is insufficient evidence at this moment in support of the hypothesis that dioxin exposure may lead to increased risk of developing endometriosis in women. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - September 14, 2009 Category: Molecular Biology Authors: Guo, S.-W., Simsa, P., Kyama, C. M., Mihalyi, A., Fulop, V., Othman, E.-E. R., D'Hooghe, T. M. Tags: New Research Horizon Reviews Source Type: journals

Epigenetics of endometriosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, several lines of evidence suggest that epigenetics plays a definite role in the pathogenesis and pathophysiology of endometriosis. As such, endometriosis is possibly treatable by rectifying epigenetic aberrations through pharmacological means. DNA methylation markers may also be useful for diagnostic and prognostic purposes. It is also possible that the delineation of the epigenetic changes accompanied by the genesis and progression of endometriosis could lead to interventions that reduce the risk of developing endometriosis. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - September 14, 2009 Category: Molecular Biology Authors: Guo, S.-W. Tags: New Research Horizon Reviews Source Type: journals

The non-human primate model of endometriosis: research and implications for fecundityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The development of an animal model of endometriosis is crucial for the investigation of disease pathogenesis and therapeutic intervention. These models will enhance our ability to evaluate the causes for the subfertility associated with disease and provide a first-line validation of treatment modulators. Currently rodents and non-human primate models have been developed, but each model has their limitations. The aim of this manuscript is to summarize the current findings and theories on the development of endometriosis and disease progression and the effectiveness of therapeutic targets using the experimental induced model...
Source: Molecular Human Reproduction - September 14, 2009 Category: Molecular Biology Authors: Braundmeier, A.G., Fazleabas, A.T. Tags: New Research Horizon Reviews Source Type: journals

Endometriosis: science and senseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - September 14, 2009 Category: Molecular Biology Authors: Winterhager, E., Fazleabas, A., Hillier, S. Tags: Editorial Source Type: journals

GRP78 as a marker of pre-eclampsia: an exploratory studyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although the exact mechanisms that lead to shallow invasion or defective trophoblastic differentiation in pre-eclampsia are still unknown, it is widely admitted that the etiology of pre-eclampsia is a defect in trophoblast invasion of the uterine spiral arteries. We have previously observed that the status of a chaperone protein, glucose regulated protein 78 (GRP78) is associated with the invasive properties of cytotrophoblastic cells; we therefore hypothesized that circulating GRP78 could serve as a diagnostic tool in pre-eclampsia. In a prospective case–control study, we quantified GRP78 autoantibodies, complexes o...
Source: Molecular Human Reproduction - August 11, 2009 Category: Molecular Biology Authors: Laverriere, A., Landau, R., Charvet, I., Irion, O., Bischof, P., Morales, M., Cohen, M. Tags: Articles Source Type: journals

Detection of novel copy number variants in uterine leiomyomas using high-resolution SNP arraysEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Uterine leiomyomas (ULs) are benign monoclonal tumors originating from myometrial tissue in the uterus. Genetic pathways that lead to myometrial transformation into leiomyomas are largely unknown. Approximately 40% of ULs are karyotypically abnormal by G-banding; however, the remaining 60% of leiomyomas do not contain cytogenetically visible genomic rearrangements. Recent technological advances such as array based comparative genomic hybridization (array CGH) and dense single nucleotide polymorphism (SNP) arrays have enabled genome-wide scanning for genomic rearrangements missed by karyotype banding analysis. In the curren...
Source: Molecular Human Reproduction - August 11, 2009 Category: Molecular Biology Authors: Bowden, W., Skorupski, J., Kovanci, E., Rajkovic, A. Tags: Articles Source Type: journals

Mutational analysis of SAL-Like 4 (SALL4) in Han Chinese women with premature ovarian failureEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Pluripotency associated transcription factor, SAL-Like 4 (SALL4), might play an important role in conferring totipotency on oocytes. In the present study, we screened SALL4 coding regions for mutations in 100 Han Chinese women with non-syndromic ovarian failure and discovered two novel non-synonymous variants in the SALL4 gene: c.541G>A (p.Val181Met) and c.2449A>G. (p.Thr817Ala). The former variant was located in an evolutionary conserved region of SALL4 protein and might affect its function. This is the first report to suggest that SALL4 might be a potential candidate gene of premature ovarian failure. (Source: Mole...
Source: Molecular Human Reproduction - August 11, 2009 Category: Molecular Biology Authors: Wang, B., Li, L., Ni, F., Song, J., Wang, J., Mu, Y., Ma, X., Cao, Y. Tags: Articles Source Type: journals

Inhibin alpha gene and susceptibility to premature ovarian failure: a data synthesisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, there is no evidence of association between the studied polymorphisms and POF. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - August 11, 2009 Category: Molecular Biology Authors: Zintzaras, E. Tags: Articles Source Type: journals

Quantification of oocyte-specific transcripts in follicle-enclosed oocytes during antral development and maturation in vitroEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study quantifies gene expression levels in relation to follicle culture time and time of oocyte maturation in a mouse model. RNA levels of Gdf-9, Bmp-15, Mater, Zar-1, Npm-2 and Fgf-8 were measured in germinal vesicle oocytes along fixed times during in vitro follicle development. For all genes, the highest mRNA levels were detected in oocytes in the pre-antral follicle stage. Antrum formation was associated with a progressive shutdown in transcription leading to mRNA values lower than those in vivo preovulatory oocytes by extending period of in vitro culture. In contrast to in vitro-matured oocytes, the in vivo oocyt...
Source: Molecular Human Reproduction - August 11, 2009 Category: Molecular Biology Authors: Sanchez, F., Adriaenssens, T., Romero, S., Smitz, J. Tags: Articles Source Type: journals

The role of centrosomes in mammalian fertilization and its significance for ICSIEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Centrosome integrity is critically important for successful fertilization and embryo development. In humans, the sperm contributes the dominant centrosomal material containing centrioles and centrosomal components onto which oocyte centrosomal proteins assemble after sperm incorporation to form the sperm aster that is essential for uniting sperm and oocyte pronuclei. Increasingly, dysfunctional sperm centrosomes have been identified as a factor for sperm-derived infertility and heterologous Intracytoplasmic Sperm Injection (ICSI) has been used to assess centrosome and sperm aster formation and clearly established a relatio...
Source: Molecular Human Reproduction - August 11, 2009 Category: Molecular Biology Authors: Schatten, H., Sun, Q.-Y. Tags: New Research Horizon Reviews Source Type: journals

New horizons for in vitro spermatogenesis? An update on novel three-dimensional culture systems as tools for meiotic and post-meiotic differentiation of testicular germ cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Culture and differentiation of male germ cells has been performed for various purposes in the past. To date, none of the studies aimed at in vitro spermatogenesis has resulted in a sufficient number of mature gametes. Numerous studies have revealed worthy pieces of information, building up a body of information on conditions that are required to maintain and mature male germ cells in vitro. In this review, we report on previously published and unpublished experiments addressing murine germ cell differentiation in three-dimensional (3D) in vitro culture systems. In a systematic set of experiments, we examined the influence ...
Source: Molecular Human Reproduction - August 11, 2009 Category: Molecular Biology Authors: Stukenborg, J.-B., Schlatt, S., Simoni, M., Yeung, C.-H., Elhija, M. A., Luetjens, C. M., Huleihel, M., Wistuba, J. Tags: New Research Horizon Reviews Source Type: journals

Estrogen receptor {beta} gene mutations in Indian infertile menEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent studies suggest that estrogens play an important role in male fertility. Estrogen signaling is mediated by Estrogen Receptors (ER and ERβ). Association of ERβ with male infertility has not been analyzed to date except for genotyping of known polymorphisms in two different studies, which yielded controversial interpretation. Hence, we performed sequencing of all the exons and untranslated regions of ERβ gene in 300 infertile and 255 fertile control Indian men. We identified eight novel mutations and four known single nucleotide polymorphisms (SNPs). Of the eight novel mutations, four were non-synonymou...
Source: Molecular Human Reproduction - July 12, 2009 Category: Molecular Biology Authors: Khattri, A., Pandey, R.K., Gupta, N.J., Chakravarty, B., Deenadayal, M., Singh, L., Thangaraj, K. Tags: ORIGINAL ARTICLES Source Type: journals

Regulation of myometrial contractivity during pregnancy in the rat: potential role for DDAHEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
There has been little information demonstrating the roles of dimethylarginine dimethylaminohydrolase (DDAH), which is the hydrolyzing enzyme of endogenous nitric oxide synthase (NOS) inhibitors and, in turn, modulates the intracellular concentrations of NOS inhibitors, in the myometrium during the course of pregnancy. Therefore, the present experiments were designed to investigate whether or not DDAH activity, protein and mRNA expression levels are altered during gestation of the rat and, if altered, those changes reflect on the levels of endogenous inhibitors and endothelin-1 (ET-1), and NO-dependent cyclic GMP generation...
Source: Molecular Human Reproduction - July 12, 2009 Category: Molecular Biology Authors: Ito, E., Obayashi, S., Nagai, A., Imamura, M., Azuma, H. Tags: ORIGINAL ARTICLES Source Type: journals

MATER protein as substrate of PKC{varepsilon} in human cumulus cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
High activity of the phosphoinositide 3-kinase/Akt pathway in cumulus cells plays an important role in FSH regulation of cell function and Protein Kinase C epsilon (PKC) collaborates with these signalling pathways to regulate cell proliferation. Relevant roles in follicular development are played by Maternal Antigen That Embryos Require (MATER) that is a cumulus cell- and oocyte-specific protein dependent on the maternal genome. We recently demonstrated that human MATER localizes at specific domains of oocytes and, for the first time, also in cumulus cells. MATER contains a carboxy-terminal leucine-rich repeat domain invol...
Source: Molecular Human Reproduction - July 12, 2009 Category: Molecular Biology Authors: Maraldi, T., Riccio, M., Sena, P., Marzona, L., Nicoli, A., La Marca, A., Marmiroli, S., Bertacchini, J., La Sala, G., De Pol, A. Tags: ORIGINAL ARTICLES Source Type: journals

The genotype of the NK cell receptor, KIR2DL4, influences INF{gamma} secretion by decidual natural killer cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study confirms that expression of KIR2DL4 by dNK is dependent on the 9A/10A polymorphism and that this polymorphism influences IFN secretion by dNK cells. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - July 12, 2009 Category: Molecular Biology Authors: Goodridge, J.P., Lathbury, L.J., John, E., Charles, A.K., Christiansen, F.T., Witt, C.S. Tags: ORIGINAL ARTICLES Source Type: journals

The pluripotency transcription factor Kruppel-like factor 4 is strongly expressed in intratubular germ cell neoplasia unclassified and seminomaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, this finding suggests that KLF4 may be an important factor for the maintenance of the developmental and the tumorigenic potential of IGCNU as well as for the malignancy of seminoma. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - July 12, 2009 Category: Molecular Biology Authors: Godmann, M., Gashaw, I., Eildermann, K., Schweyer, S., Bergmann, M., Skotheim, R.I., Behr, R. Tags: ORIGINAL ARTICLES Source Type: journals

Abnormal methylation at the KvDMR1 imprinting control region in clinically normal children conceived by assisted reproductive technologiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genomic imprinting alterations have been shown to be associated with assisted reproductive technologies (ARTs) in animals. At present, data obtained in humans are inconclusive; however, some epidemiological studies have demonstrated an increased incidence of imprinting disorders in children conceived by ARTs. In the present study, we focused on the effect of ARTs [IVF and intracytoplasmic sperm injection (ICSI)] on the epigenetic reprogramming of the maternally methylated imprinting control region KvDMR1 in clinically normal children. Qualitative and quantitative methylation at KvDMR1 were assessed by the methylation-speci...
Source: Molecular Human Reproduction - July 12, 2009 Category: Molecular Biology Authors: Gomes, M.V., Huber, J., Ferriani, R.A., Amaral Neto, A.M., Ramos, E.S. Tags: ORIGINAL ARTICLES Source Type: journals

PDE8A genetic variation, polycystic ovary syndrome and androgen levels in womenEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Polycystic ovary syndrome (PCOS) is characterized by excessive theca cell androgen secretion, dependent upon LH, which acts through the intermediacy of 3',5'-cyclic adenosine monophosphate (cAMP). cAMP signaling pathways are controlled through regulation of its synthesis by adenylyl cyclases, and cAMP degradation by phosphodiesterases (PDEs). PDE8A, a high-affinity cAMP-specific PDE is expressed in the ovary and testis. Leydig cells from mice with a targeted mutation in the Pde8a gene are sensitized to the action of LH in terms of testosterone production. These observations led us to evaluate the human PDE8A gene as a PCOS...
Source: Molecular Human Reproduction - July 12, 2009 Category: Molecular Biology Authors: Chen, C., Wickenheisser, J., Ewens, K. G., Ankener, W., Legro, R. S., Dunaif, A., McAllister, J. M., Spielman, R. S., Strauss, J. F. Tags: ORIGINAL ARTICLES Source Type: journals

Thrombin and interleukin-1{beta} decrease HOX gene expression in human first trimester decidual cells: implications for pregnancy lossEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, multiple HOX genes are expressed in decidual cells and inhibited by thrombin and IL-1β. Since HOXA10 and HOXA11 are known to be necessary for successful pregnancy, these findings suggest a molecular mechanism by which bleeding or inflammation may affect pregnancy outcome. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - June 14, 2009 Category: Molecular Biology Authors: Sarno, J., Schatz, F., Huang, S. J., Lockwood, C., Taylor, H. S. Tags: Articles Source Type: journals

ROCK2 allelic variants are not associated with pre-eclampsia susceptibility in the Finnish populationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The rho-associated coiled-coil protein kinase 2 (ROCK2) gene has been suggested to associate with general hypertension and is therefore a plausible functional candidate gene for pre-eclampsia. ROCK2 maps to chromosome 2p25, which we have implicated previously in a linkage study of pre-eclampsia. We have re-sequenced exons and putative promoter region of ROCK2 in up to 30 pre-eclampsia patients and 22 controls and genotyped putative functional single-nucleotide polymorphisms (SNPs) as well as tagging SNPs from HapMap in a Finnish case–control data set—340 affected and 357 matched control individuals—for a ...
Source: Molecular Human Reproduction - June 14, 2009 Category: Molecular Biology Authors: Peterson, H., Laivuori, H., Kerkela, E., Jiao, H., Hiltunen, L., Heino, S., Tiala, I., Knuutila, S., Rasi, V., Kere, J., Kivinen, K. Tags: Articles Source Type: journals

Protein processing by the placental protease, cathepsin PEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cathepsin P is a member of a family of placentally expressed cathepsins (PECs). The closest human homolog of cathepsin P is cathepsin L, a broad specificity enzyme that has functions in many tissues in addition to placenta. The gene duplications that gave rise to the PECs provide a rare opportunity to define proteolytic functions in placenta, a transient organ unique to mammals. Peptidyl substrate and inhibitor libraries have shown that cathepsin P has evolved an unusually restricted preference for substrates containing hydrophobic amino acids. Proteomic techniques were used to probe for substrates of this enzyme. Recombin...
Source: Molecular Human Reproduction - June 14, 2009 Category: Molecular Biology Authors: Hassanein, M., Bojja, A. S., Glazewski, L., Lu, G., Mason, R.W. Tags: Articles Source Type: journals

The effects of metformin on uterine tissue of hyperandrogenized BALB/c miceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The present study investigated the role of the N, N'-dimethylbiguanide metformin (50 mg/kg body weight in 0.05 ml water, given orally with a canulla) in preventing the adverse effects generated by hyperandrogenism on uterine function. Daily injection of dehydroepiandrosterone (DHEA: 6 mg/100 g body weight in 0.1 ml oil) for 20 consecutive days induces polycystic ovaries in BALB/c mice. In this model we found that DHEA produced alterations on uterine histology closely related to the development of pre-cancerous structures concomitantly with increased incidence of uterine apoptosis. The injection of DHEA induced a pro-inflam...
Source: Molecular Human Reproduction - June 14, 2009 Category: Molecular Biology Authors: Elia, E. M., Belgorosky, D., Faut, M., Vighi, S., Pustovrh, C., Luigi, D., Motta, A. B. Tags: Articles Source Type: journals

Superoxide dismutase expression in human cumulus oophorus cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Success in assisted reproductive techniques (ART) is influenced by gamete and embryo quality but the assessment of these parameters has been thwarted by the lack of reliable biomarkers. Follicular fluid and cumulus oophorus cells may provide biomarkers due to their close relationship to the oocyte. These cells produce antioxidants and thus protect the oocyte from oxidative damage exerted by reactive oxygen species (ROS). ROS and antioxidants are known to intervene in reproductive physiology and pathology, but their roles are unclear. It is hypothesized that superoxide dismutase (SOD), a first line antioxidant enzyme, is as...
Source: Molecular Human Reproduction - June 14, 2009 Category: Molecular Biology Authors: Matos, L., Stevenson, D., Gomes, F., Silva-Carvalho, J.L., Almeida, H. Tags: Articles Source Type: journals

The signal pathway of gonadotrophins-induced mammalian oocyte meiotic resumptionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Fully grown mammalian oocytes are arrested at the first meiotic prophase until a surge of gonadotrophin at the mid-cycle. The actions of gonadotrophins, follicle stimulating hormone (FSH) and luteinizing hormone (LH), on oocyte meiotic resumption are believed to be mediated in large part through increasing the production of cyclic adenosine 3',5'-monophosphate and subsequent activation of mitogen-activated protein kinase (MAPK) in its surrounding cumulus granulosa cells. Recent findings indicate that gonadotrophins-induced epidermal growth factor-like growth factors, meiosis activating sterol and gonadal steroid hormones, ...
Source: Molecular Human Reproduction - June 14, 2009 Category: Molecular Biology Authors: Zhang, M., Ouyang, H., Xia, G. Tags: New Research Horizon Review Source Type: journals

Purification of germline stem cells from adult mammalian ovaries: a step closer towards control of the female biological clock?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
For decades it was believed that a non-renewable pool of oocyte-containing follicles is established in female mammals at birth. This cornerstone of reproductive biology was challenged 5 years ago by a study reporting on the presence of mitotically-active germ cells in juvenile and adult mouse ovaries. Additional findings presented in this study and others that followed further suggested that mammals retain the capacity to generate oocytes during adulthood; however, isolation of oocyte-producing germline stem cells (GSC) as unequivocal proof of their existence remained elusive. This piece of information now appears to have ...
Source: Molecular Human Reproduction - June 14, 2009 Category: Molecular Biology Authors: Tilly, J. L., Telfer, E. E. Tags: Commentary Source Type: journals