Progress towards human primordial germ cell specification in vitro
This article describes the latest, most relevant findings about the mechanisms of PGC formation, emphasizing human PGC. It also discusses our own laboratory's progress in using transdifferentiation protocols to derive human PGCs (hPGCs). Our preliminary results arose from our pursuit of a sequential hPGC induction strategy that starts with the repression of lineage-specific factors in the somatic cell, followed by the reactivation of germ cell-related genes using specific master regulators, which can indeed reactivate germ cell-specific genes in somatic cells. While it is still premature to assume that fully functional hum...
Source: Molecular Human Reproduction - January 3, 2017 Category: Molecular Biology Source Type: research

Inhibin-B secretion and FSH isoform distribution may play an integral part of follicular selection in the natural menstrual cycle
<span class="paragraphSection"><div class="boxTitle">Abstract</div>The aim of the present paper is to expand the concept on how follicular selection takes place in the follicular phase of the natural menstrual cycle. It is suggested that inhibin-B exerts a more intimate role in this process than previously understood. Inhibin-B shows a peak in the circulation around cycle day 7, simultaneous with selection of the dominant follicle, whereas levels of estradiol and inhibin-A only start to increase a few days later suggesting that inhibin-B is mainly responsible for downregulating pituitary FSH release. New ...
Source: Molecular Human Reproduction - January 3, 2017 Category: Molecular Biology Source Type: research

Antigen unmasking enhances visualization efficacy of the oocyte activation factor, phospholipase C zeta, in mammalian sperm
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Study Question</div>Is it possible to improve clinical visualization of phospholipase C zeta (PLCζ) as a diagnostic marker of sperm oocyte activation capacity and male fertility?<div class="boxTitle">Summary Answer</div>Poor PLCζ visualization efficacy using current protocols may be due to steric or conformational occlusion of native PLCζ, hindering antibody access, and is significantly enhanced using antigen unmasking/retrieval (AUM) protocols.<div class="boxTitle">What is Known Alrea...
Source: Molecular Human Reproduction - January 3, 2017 Category: Molecular Biology Source Type: research

Normalization matters: tracking the best strategy for sperm miRNA quantification
This study is focused on sperm miRNA qRT-PCR analysis. The use of the selected normalizers in other cell types or tissues would still require confirmation.<div class="boxTitle">Wider Implications of the Findings</div>The search for new fertility biomarkers based on sperm miRNA expression using high-throughput assays is one of the upcoming challenges in the field of reproductive genetics. In this context, validation of the results using singleplex assays would be mandatory. The normalizer strategy suggested in this study would provide a universal option in this area, allowing for normalization of the validated d...
Source: Molecular Human Reproduction - January 3, 2017 Category: Molecular Biology Source Type: research

Down-regulation of the liver-derived plasma protein fetuin-B mediates reversible female infertility
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Study question</div>Does antisense oligonucleotide (ASO)-mediated down-regulation of serum fetuin-B cause infertility like fetuin-B gene deficiency in female mice?<div class="boxTitle">Summary answer</div>Pharmacological fetuin-B down-regulation by ASO therapy results in reversible infertility in female mice.<div class="boxTitle">What is known already</div>Female fetuin-B deficient (<span style="font-style:italic;">Fetub</span><sup>−/−</sup>) mice are inf...
Source: Molecular Human Reproduction - January 3, 2017 Category: Molecular Biology Source Type: research

Recombinant fetuin-B protein maintains high fertilization rate in cumulus cell-free mouse oocytes
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Study Question</div>Does fetuin-B inhibit premature zona pellucida (ZP) hardening in mouse oocytes <span style="font-style:italic;">in vitro</span> and thus increase IVF rate?<div class="boxTitle">Summary Answer</div>Supplementation of oocyte <span style="font-style:italic;">in vitro</span> maturation (IVM) media with recombinant mouse fetuin-B (rmFetuB) increased fertilization rate without affecting mouse embryo development into blastocysts.<div class="boxTitle">W...
Source: Molecular Human Reproduction - January 3, 2017 Category: Molecular Biology Source Type: research

Bone morphogenetic protein 2 regulates cell–cell communication by down-regulating connexin43 expression in luteinized human granulosa cells
This study also represents the first comprehensive research of molecular mechanisms of BMP2 in the down-regulation Cx43 in luteinized human granulosa cells. Such data may provide valuable insights into ovarian physiology and benefit the development of potential therapeutic methods for patients suffering from luteal insufficiency.<div class="boxTitle">LARGE SCALE DATA</div>N/A.<div class="boxTitle">STUDY FUNDING AND COMPETING INTEREST(s)</div>This research was supported by an operating grant from the China-Canadian Joint Health Research Initiative Grants Program to P.C.K. Leung and J.Z. Sheng. The au...
Source: Molecular Human Reproduction - December 27, 2016 Category: Molecular Biology Source Type: research

Placental-specific sFLT-1: role in pre-eclamptic pathophysiology and its translational possibilities for clinical prediction and diagnosis
<span class="paragraphSection"><div class="boxTitle">Abstract</div>Pre-eclampsia is a common obstetric complication globally responsible for a significant burden of maternal and perinatal morbidity and mortality. Central to its pathophysiology is the anti-angiogenic protein, soluble fms-like tyrosine kinase-1 (sFLT-1). sFLT-1 is released from a range of tissues into the circulation, where it antagonizes the activity of vascular endothelial growth factor and placental growth factor leading to endothelial dysfunction. It is this widespread endothelial dysfunction that produces the clinical features of pre-e...
Source: Molecular Human Reproduction - December 27, 2016 Category: Molecular Biology Source Type: research

Spermaurin, an La1-like peptide from the venom of the scorpion Scorpio maurus palmatus , improves sperm motility and fertilization in different mammalian species
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">STUDY QUESTION</div>Is it possible to identify original compounds that are able to enhance sperm motility from the venom of the scorpion <span style="font-style:italic;">Scorpio maurus palmatus</span>?<div class="boxTitle">SUMMARY ANSWER</div>We identified a potent disulfide-rich peptide (DRP) of 73 amino acids that significantly improved the motility of fresh and frozen-thawed sperm in different mammalian species, including human, and improved fertilization outcome in mouse IVF exp...
Source: Molecular Human Reproduction - December 27, 2016 Category: Molecular Biology Source Type: research

Microfluidic analysis of oocyte and embryo biomechanical properties to improve outcomes in assisted reproductive technologies
<span class="paragraphSection"><div class="boxTitle">Abstract</div>Measurement of oocyte and embryo biomechanical properties has recently emerged as an exciting new approach to obtain a quantitative, objective estimate of developmental potential. However, many traditional methods for probing cell mechanical properties are time consuming, labor intensive and require expensive equipment. Microfluidic technology is currently making its way into many aspects of assisted reproductive technologies (ART), and is particularly well suited to measure embryo biomechanics due to the potential for robust, automated si...
Source: Molecular Human Reproduction - December 8, 2016 Category: Molecular Biology Source Type: research

Identification of genes differentially expressed in menstrual breakdown and repair
STUDY QUESTION Does the changing molecular profile of the endometrium during menstruation correlate with the histological profile of menstruation. SUMMARY ANSWER We identified several genes not previously associated with menstruation; on Day 2 of menstruation (early-menstruation), processes related to inflammation are predominantly up-regulated and on Day 4 (late-menstruation), the endometrium is predominantly repairing and regenerating. WHAT IS KNOWN ALREADY Menstruation is induced by progesterone withdrawal at the end of the menstrual cycle and involves endometrial tissue breakdown, regeneration and repair. Perturbatio...
Source: Molecular Human Reproduction - December 6, 2016 Category: Molecular Biology Authors: Paiva, P., Lockhart, M. G., Girling, J. E., Olshansky, M., Woodrow, N., Marino, J. L., Hickey, M., Rogers, P. A. W. Tags: Original research Source Type: research

Differences in cumulus cell gene expression indicate the benefit of a pre-maturation step to improve in-vitro bovine embryo production
This study was conducted with bovine samples. Whether or not the results are applicable to human oocytes requests further elucidation. Embryo transfer experiments are required to determine whether the improvement in blastocyst rates in the tailored system leads to increased live birth rates. WIDER IMPLICATIONS OF THE FINDINGS The identification of multiple non-invasive biomarkers predictive of oocyte quality can greatly strengthen the pre-IVM approach aimed to improve IVM outcomes. These results have potentially important implications in treating human infertility and in developing breeding schemes for domestic mammals. ...
Source: Molecular Human Reproduction - December 6, 2016 Category: Molecular Biology Authors: Dieci, C., Lodde, V., Labreque, R., Dufort, I., Tessaro, I., Sirard, M.-A., Luciano, A. M. Tags: Original research Source Type: research

Improved cryotolerance and developmental potential of in vitro and in vivo matured mouse oocytes by supplementing with a glutathione donor prior to vitrification
STUDY QUESTION Can supplementation of media with a glutathione (GSH) donor, glutathione ethyl ester (GEE), prior to vitrification protect the mouse oocyte from oxidative damage and critical changes in redox homeostasis, and thereby improve cryotolerance? SUMMARY ANSWER GEE supplementation supported redox regulation, rapid recovery of spindle and chromosome alignment after vitrification/warming and improved preimplantation development of mouse metaphase II (MII) oocytes. WHAT IS KNOWN ALREADY Cryopreservation may affect mitochondrial functionality, induce oxidative stress, and thereby affect spindle integrity, chromosome ...
Source: Molecular Human Reproduction - December 6, 2016 Category: Molecular Biology Authors: Trapphoff, T., Heiligentag, M., Simon, J., Staubach, N., Seidel, T., Otte, K., Fröhlich, T., Arnold, G. J., Eichenlaub-Ritter, U. Tags: Original research Source Type: research

Sphingosine-1-phosphate restores endothelial barrier integrity in ovarian hyperstimulation syndrome
StUDY QUESTION Are follicular fluid (FF) sphingosine-1-phosphate (S1P) levels in patients at risk of developing ovarian hyperstimulation syndrome (OHSS) altered and in part responsible for the high vascular permeability observed in these patients. STUDY ANSWER FF S1P levels are lower in FF from patients at risk of OHSS and treatment with S1P may reduce vascular permeability in these patients. WHAT IS KNOWN ALREADY Although advances have been made in the diagnosis, and management of OHSS and in basic knowledge of its development, complete prevention has proven difficult. StUDY DESIGN, SIZE, DURATION A total of 40 FF aspi...
Source: Molecular Human Reproduction - December 6, 2016 Category: Molecular Biology Authors: Scotti, L., Di Pietro, M., Pascuali, N., Irusta, G., I de Zuniga, , Gomez Pena, M., Pomilio, C., Saravia, F., Tesone, M., Abramovich, D., Parborell, F. Tags: Original research Source Type: research

A grafted ovarian fragment rescues host fertility after chemotherapy
STUDY QUESTION Can host fertility be rescued by grafting of a fragment of a healthy ovary soon after chemotherapy? SUMMARY ANSWER We found that grafting a green fluorescent protein (GFP)-positive fragment from a healthy isogenic ovary to the left ovary of a chemo-treated host rescued function and fertility of the grafted host ovary, and resulted in the production of host-derived offspring as late as the sixth litter after chemotherapy (CTx) treatment, whereas none of the ungrafted controls produced a second litter. WHAT IS KNOWN ALREADY In women and girls undergoing chemotherapy, infertility and premature ovarian failure...
Source: Molecular Human Reproduction - December 6, 2016 Category: Molecular Biology Authors: Batchvarov, I. S., Taylor, R. W., Bustamante-Marin, X., Czerwinski, M., Johnson, E. S., Kornbluth, S., Capel, B. Tags: Original research Source Type: research