Microfluidics for mammalian embryo culture and selection: where do we stand now?
<span class="paragraphSection"><div class="boxTitle">Abstract</div>The optimization of <span style="font-style:italic;">in-vitro</span> culture conditions and the selection of the embryo(s) with the highest developmental competence are essential components in an ART program. Culture conditions are manifold and they underlie not always evidence-based research but also trends entering the IVF laboratory. At the moment, the idea of using sequential media according to the embryo requirements has been given up in favor of the use of single step media in an uninterrupted manner due to practical issu...
Source: Molecular Human Reproduction - October 4, 2016 Category: Molecular Biology Source Type: research

A dominant negative mutation at the ATP binding domain of AMHR2 is associated with a defective anti-Müllerian hormone signaling pathway
STUDY QUESTION Does a heterozygous mutation in AMHR2, identified in whole-exome sequencings (WES) of patients with primary ovarian insufficiency (POI), cause a defect in anti-Müllerian hormone (AMH) signaling? SUMMARY ANSWER The I209N mutation at the adenosine triphosphate binding domain of AMHR2 exerts dominant negative defects in the AMH signaling pathway. WHAT IS KNOWN ALREADY Previous studies have demonstrated the associations of several sequence variants in AMH or AMHR2 with POI, but no functional assay has been performed to verify whether there was any defect on AMH signaling. STUDY DESIGN, SAMPLES/MA...
Source: Molecular Human Reproduction - September 6, 2016 Category: Molecular Biology Authors: Li, L., Zhou, X., Wang, X., Wang, J., Zhang, W., Wang, B., Cao, Y., Kee, K. Tags: Original article Source Type: research

Decreased expression of NR4A nuclear receptors in adenomyosis impairs endometrial decidualization
This study was supported by the National Natural Science Foundation of China (81170570, G.J.Y. 81370683, G.J.Y. 81501251, Y.J. 31571189, H.X.S. and 81571402, G.J.Y.), and a special grant for clinical medicine science of Jiangsu Province (BL2014003, H.X.S.). The authors have no conflicts of interest to declare. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - September 6, 2016 Category: Molecular Biology Authors: Jiang, Y., Jiang, R., Cheng, X., Zhang, Q., Hu, Y., Zhang, H., Cao, Y., Zhang, M., Wang, J., Ding, L., Diao, Z., Sun, H., Yan, G. Tags: Original article Source Type: research

ID2 mediates the transforming growth factor-{beta}1-induced Warburg-like effect seen in the peritoneum of women with endometriosis
STUDY QUESTION Is inhibitor of DNA-binding protein 2 (ID2) a mediator of the transforming growth factor (TGF)-β1-induced Warburg-like effect seen in the peritoneum of women with endometriosis? SUMMARY ANSWER The TGF-β1-induced changes in the metabolic phenotype of peritoneal mesothelial cells from women with endometriosis are mediated through the ID2 pathway. WHAT IS KNOWN ALREADY TGF-β1 induces the metabolic conversion of glucose to lactate via aerobic glycolysis (the ‘Warburg effect’) in the peritoneum of women with endometriosis, through increased expression of the transcription factor hypox...
Source: Molecular Human Reproduction - September 6, 2016 Category: Molecular Biology Authors: Young, V. J., Ahmad, S. F., Brown, J. K., Duncan, W. C., Horne, A. W. Tags: Original article Source Type: research

P66Shc, a key regulator of metabolism and mitochondrial ROS production, is dysregulated by mouse embryo culture
This study associates embryonic p66Shc expression levels with metabolic abnormalities but does not directly implicate p66Shc in metabolic changes. Additionally, we used one formulation of embryo culture medium that differs from that used in other mouse model studies and from clinical media used to support human blastocyst development. Our findings may, therefore, be limited to this media, or may be a species-specific phenomenon. WIDER IMPLICATIONS OF THE FINDINGS This is the first study to show distinct immunolocalization of p66Shc to the trophectoderm of mouse blastocysts and that its levels are abnormally increased in e...
Source: Molecular Human Reproduction - September 6, 2016 Category: Molecular Biology Authors: Edwards, N. A., Watson, A. J., Betts, D. H. Tags: Original article Source Type: research

BMP signalling in human fetal ovary somatic cells is modulated in a gene-specific fashion by GREM1 and GREM2
This study extends previous work identifying germ cells as targets of ovarian BMP signalling, and suggests BMPs may regulate the development of both germ and somatic cells in the developing ovary around the time of follicle formation. LARGE SCALE DATA Not applicable. STUDY FUNDING/COMPETING INTERESTS This work was supported by The UK Medical Research Council (Grant No.: G1100357 to RAA), and Medical Research Scotland (Grant No. 345FRG to AJC). The authors have no competing interests to declare. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - September 6, 2016 Category: Molecular Biology Authors: Bayne, R. A., Donnachie, D. J., Kinnell, H. L., Childs, A. J., Anderson, R. A. Tags: Original article Source Type: research

Oocyte-specific deletion of N-WASP does not affect oocyte polarity, but causes failure of meiosis II completion
STUDY QUESTION There is an unexplored physiological role of N-WASP (neural Wiskott-Aldrich syndrome protein) in oocyte maturation that prevents completion of second meiosis. SUMMARY ANSWER In mice, N-WASP deletion did not affect oocyte polarity and asymmetric meiotic division in first meiosis, but did impair midbody formation and second meiosis completion. WHAT IS KNOWN ALREADY N-WASP regulates actin dynamics and participates in various cell activities through the RHO-GTPase-Arp2/3 (actin-related protein 2/3 complex) pathway, and specifically the Cdc42 (cell division cycle 42)-N-WASP-Arp2/3 pathway. Differences in the fu...
Source: Molecular Human Reproduction - September 6, 2016 Category: Molecular Biology Authors: Wang, Z.-B., Ma, X.-S., Hu, M.-W., Jiang, Z.-Z., Meng, T.-G., Dong, M.-Z., Fan, L.-H., Ouyang, Y.-C., Snapper, S. B., Schatten, H., Sun, Q.-Y. Tags: Original article Source Type: research

In vitro differentiation of rat spermatogonia into round spermatids in tissue culture
STUDY QUESTION Do the organ culture conditions, previously defined for in vitro murine male germ cell differentiation, also result in differentiation of rat spermatogonia into post-meiotic germ cells exhibiting specific markers for haploid germ cells? SUMMARY ANSWER We demonstrated the differentiation of rat spermatogonia into post-meiotic cells in vitro, with emphasis on exhibiting, protein markers described for round spermatids. WHAT IS KNOWN ALREADY Full spermatogenesis in vitro from immature germ cells using an organ culture technique in mice was first reported 5 years ago. However, no studies reporting the different...
Source: Molecular Human Reproduction - September 6, 2016 Category: Molecular Biology Authors: Reda, A., Hou, M., Winton, T. R., Chapin, R. E., Söder, O., Stukenborg, J.- B. Tags: Original article Source Type: research

Integration of microfluidics in animal in vitro embryo production
<span class="paragraphSection"><div class="boxTitle">Abstract</div>The <span style="font-style:italic;">in vitro</span> production of livestock embryos is central to several areas of animal biotechnology. Further, the use of <span style="font-style:italic;">in vitro</span> embryo manipulation is expanding as new applications emerge. ARTs find direct applications in increasing genetic quality of livestock, producing transgenic animals, cloning, artificial insemination, reducing disease transmission, preserving endangered germplasm, producing chimeric animals for disease research, an...
Source: Molecular Human Reproduction - August 17, 2016 Category: Molecular Biology Source Type: research

Branched-chain amino acids regulate insulin-like growth factor-binding protein 1 (IGFBP1) production by decidua and influence trophoblast migration through IGFBP1
STUDY QUESTION Do branched-chain amino acids (BCAAs) influence the migration of human extravillous trophoblast (EVT) cells through changes in insulin-like growth factor-binding protein 1 (IGFBP1) production in decidual cells? STUDY FINDING Decidua-derived IGFBP1 had a stimulating effect on migration of EVT. WHAT IS KNOWN ALREADY IGFBP1 is abundantly secreted from human decidual cells and influences trophoblast migration in human placenta of early pregnancy. In hepatic cells, the expression of IGFBP1 is influenced by nutritional status and BCAAs regulate IGFBP1 production. STUDY DESIGN, SAMPLES/MATERIALS, METHODS This is...
Source: Molecular Human Reproduction - August 11, 2016 Category: Molecular Biology Authors: Tanaka, K., Sakai, K., Matsushima, M., Matsuzawa, Y., Izawa, T., Nagashima, T., Furukawa, S., Kobayashi, Y., Iwashita, M. Tags: Original Research Source Type: research

The study of progesterone action in human myometrial explants
STUDY HYPOTHESIS Myometrial explants represent a superior model compared with cell culture models for the study of human myometrial progesterone (P4) signalling in parturition. STUDY FINDING Gene expression analysis showed myometrial explants closely resemble the in vivo condition and the anti-inflammatory action of P4 is not lost with labour onset. WHAT IS KNOWN ALREADY Circulating P4 levels decline before the onset of parturition in most animals, but not in humans. This has led to the suggestion that there is a functional withdrawal of P4 action at the myometrial level prior to labour onset. However, to date, no eviden...
Source: Molecular Human Reproduction - August 11, 2016 Category: Molecular Biology Authors: Georgiou, E. X., Lei, K., Lai, P. F., Yulia, A., Herbert, B. R., Castellanos, M., May, S. T., Sooranna, S. R., Johnson, M. R. Tags: Original Research Source Type: research

Transcriptome analysis of human cumulus cells reveals hypoxia as the main determinant of follicular senescence
This study focused almost exclusively on assessing the genetic differences in CC transcriptome between young and older women. These genetic findings were not fully correlated with embryonic development and clinical outcome. Wider implications of the findings Our data provide a new hypothesis—follicular hypoxia—as the main mechanism leading to ovarian follicular senescence and suggest a link between cumulus cell aging and oocyte quality decay. If specific molecular findings of hypoxia would be confirmed also in oocytes, genetic platforms could screen CC for hypoxic damage and identify healthier oocytes. Protoco...
Source: Molecular Human Reproduction - August 11, 2016 Category: Molecular Biology Authors: Molinari, E., Bar, H., Pyle, A. M., Patrizio, P. Tags: Original Research Source Type: research

Developmental origins of inflammatory and immune diseases
Epidemiological and experimental animal studies show that suboptimal environments in fetal and neonatal life exert a profound influence on physiological function and risk of diseases in adult life. The concepts of the ‘developmental programming’ and Developmental Origins of Health and Diseases (DOHaD) have become well accepted and have been applied across almost all fields of medicine. Adverse intrauterine environments may have programming effects on the crucial functions of the immune system during critical periods of fetal development, which can permanently alter the immune function of offspring. Immune dysfu...
Source: Molecular Human Reproduction - August 11, 2016 Category: Molecular Biology Authors: Chen, T., Liu, H.-x., Yan, H.-y., Wu, D.-m., Ping, J. Tags: New Research Horizon Review Source Type: research

The why, the how and the when of PGS 2.0: current practices and expert opinions of fertility specialists, molecular biologists, and embryologists
STUDY QUESTION We wanted to probe the opinions and current practices on preimplantation genetic screening (PGS), and more specifically on PGS in its newest form: PGS 2.0? STUDY FINDING Consensus is lacking on which patient groups, if any at all, can benefit from PGS 2.0 and, a fortiori, whether all IVF patients should be offered PGS. WHAT IS KNOWN ALREADY It is clear from all experts that PGS 2.0 can be defined as biopsy at the blastocyst stage followed by comprehensive chromosome screening and possibly combined with vitrification. Most agree that mosaicism is less of an issue at the blastocyst stage than at the cleavage...
Source: Molecular Human Reproduction - August 11, 2016 Category: Molecular Biology Authors: Sermon, K., Capalbo, A., Cohen, J., Coonen, E., De Rycke, M., De Vos, A., Delhanty, J., Fiorentino, F., Gleicher, N., Griesinger, G., Grifo, J., Handyside, A., Harper, J., Kokkali, G., Mastenbroek, S., Meldrum, D., Meseguer, M., Montag, M., Munne, S., Rie Tags: New Research Horizon Review Source Type: research

Preimplantation genetic screening 2.0: the theory
In conclusion, the introduction of PGS 2.0 will depend on the success of the new biopsy strategies in combination with the analysis of all 24 chromosomes. It remains to be seen which approach will be the most successful and for which specific groups of patients. (Source: Molecular Human Reproduction)
Source: Molecular Human Reproduction - August 11, 2016 Category: Molecular Biology Authors: Geraedts, J., Sermon, K. Tags: New Research Horizon Review Source Type: research