2,589 results match your criteria MHR: Basic Science of Reproductive Medicine [Journal]


Generation of immortalized human endometrial stromal cell lines with different endometriosis risk genotypes.

Mol Hum Reprod 2019 Feb 16. Epub 2019 Feb 16.

Department of Obstetrics and Gynaecology and Gynaecology Research Centre, Royal Women's Hospital, University of Melbourne, Parkville, Victoria, Australia.

Endometriotic lesions are composed in part of endometrial-like stromal cells, however, there is a shortage of immortalized human endometrial stromal cultures available for research. As genetic factors play a role in endometriosis risk, it is important that genotype is also incorporated into analysis of pathological mechanisms. Human telomerase reverse transcriptase (hTERT) immortalization (using Lenti-hTERT-green fluorescent protein virus) took place following genotype selection; 13 patients homozygous for either the risk or non-risk 'other' allele for one or more important endometriosis risk single nucleotide polymorphism on chromosome 1p36. Read More

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http://dx.doi.org/10.1093/molehr/gaz006DOI Listing
February 2019
1 Read

Genes Upregulated in the Amnion at Labour are Bivalently Marked by Activating and Repressive Histone Modifications.

Mol Hum Reprod 2019 Feb 12. Epub 2019 Feb 12.

Mothers and Babies Research Centre, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia.

Inflammatory genes are expressed increasingly in the fetal membranes at late gestation triggering birth. Here we have examined whether epigenetic histone modifications contribute to the upregulation of proinflammatory genes in the amnion in late pregnancy and at labour. Amnion samples were collected from early pregnancy, at term in the absence of labour and after spontaneous birth. Read More

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http://dx.doi.org/10.1093/molehr/gaz007DOI Listing
February 2019
1 Read

The role of oxygen in regulating microRNAs in control of the placental renin-angiotensin system.

Mol Hum Reprod 2019 Feb 6. Epub 2019 Feb 6.

Priority Research Centre for Reproductive Sciences, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, New South Wales, Australia.

Human placental renin-angiotensin system (RAS) expression is highest in early gestation, at a time when placental oxygen tension is at its lowest (1-3%), and promotes placental development. Some miRNAs predicted to target RAS mRNAs are downregulated in early gestation. We tested the hypothesis that low oxygen suppresses expression of miRNAs that target placental RAS mRNAs, thus increasing concentrations of RAS mRNAs. Read More

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http://dx.doi.org/10.1093/molehr/gaz004DOI Listing
February 2019

Combined proteomic and miRNome analyses of mouse testis exposed to an endocrine disruptors chemicals mixture reveals altered toxicological pathways involved in male infertility.

Mol Hum Reprod 2019 Jan 30. Epub 2019 Jan 30.

Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas C.I.B. (CSIC), Madrid, Spain.

The increase in male idiopathic infertility has been associated with daily exposure to endocrine disruptors chemicals (EDCs). Nevertheless, the mechanisms of action in relation to dysregulating proteins and regulatory microRNAs are unknown.We combined proteomic and miRNome analyses of mouse testis chronically exposed to low doses of a define mixture of EDCs [phthalates: bis (2-ethylhexyl), dibutyl and benzyl-butyl; 4-nonylphenol and 4-tert-octylphenol], administered in the drinking water from conception until adulthood (post-natal day 60/75) and compared them with no-exposed control mice. Read More

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http://dx.doi.org/10.1093/molehr/gaz003DOI Listing
January 2019
1 Read
3.747 Impact Factor

Temporal patterns of gene regulation and upstream regulators contributing to major developmental transitions during Rhesus macaque preimplantation development.

Mol Hum Reprod 2019 Jan 30. Epub 2019 Jan 30.

Department of Animal Science and Reproductive and Developmental Sciences Program, Michigan State University.

The preimplantation period of life in mammals encompasses a tremendous amount of restructuring and remodeling of the embryonic genome and reprogramming of gene expression. These vast changes support metabolic activation and cellular processes that drive early cleavage divisions and enable the creation of the earliest primitive cell lineages. A major question in mammalian embryology is how such vast, sweeping changes in gene expression are orchestrated, so that changes in gene expression are exactly appropriate to meet the developmental needs of the embryo over time. Read More

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http://dx.doi.org/10.1093/molehr/gaz001DOI Listing
January 2019

Involvement of endoplasmic reticulum stress in regulation of endometrial stromal cell invasiveness: Possible role in pathogenesis of endometriosis.

Mol Hum Reprod 2019 Jan 18. Epub 2019 Jan 18.

Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, Korea.

Endoplasmic reticulum (ER) stress is known to reduce invasiveness in some cancer cells by inhibiting the AKT/mTOR pathway. A previous study from our laboratory suggested that ER stress is promoted by progesterone in human endometrial cells, which suggests that progesterone may inhibit endometrial cell invasiveness by up-regulating ER stress. Therefore, aberrant ER stress in response to progesterone may contribute to the altered invasiveness found in endometriotic tissues. Read More

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https://academic.oup.com/molehr/advance-article/doi/10.1093/
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http://dx.doi.org/10.1093/molehr/gaz002DOI Listing
January 2019
2 Reads

Membrane bound Glucose Regulated Protein 78 interacts with alpha-2-macroglobulin to promote actin reorganization in sperm during epididymal maturation.

Mol Hum Reprod 2018 Dec 24. Epub 2018 Dec 24.

Department of Gamete Immunobiology, ICMR- National Institute for Research in Reproductive Health, Mumbai 400012, India.

Glucose regulated protein 78 (GRP78) is expressed on cell surface in exceptional conditions as seen in cancer cells and macrophages. We have reported its membrane localization in sperm. The functional significance of its surface localization in sperm is an enigma. Read More

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http://dx.doi.org/10.1093/molehr/gay055DOI Listing
December 2018
2 Reads

Gonadotrophin-mediated miRNA expression in testis at onset of puberty in rhesus monkey: predictions on regulation of thyroid hormone activity and DLK1-DIO3 locus.

Mol Hum Reprod 2018 Dec 24. Epub 2018 Dec 24.

Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine and Magee-Womens Research Institute, Pittsburgh, PA 15213, USA.

Molecular mechanisms responsible for initiation of primate spermatogenesis remain poorly characterized. Previously, 48 h stimulation of the testes of three juvenile rhesus monkeys with pulsatile LH and FSH resulted in down-regulation of a cohort of genes recognized to favor spermatogonia stem cell renewal. This change in genetic landscape occurred in concert with amplification of Sertoli cell proliferation and the commitment of undifferentiated spermatogonia to differentiate. Read More

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http://dx.doi.org/10.1093/molehr/gay054DOI Listing
December 2018
2 Reads

ZEB2, a master regulator of the epithelial-mesenchymal transition, mediates trophoblast differentiation.

Mol Hum Reprod 2019 Feb;25(2):61-75

Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine and Surgery and Center for Abnormal Placentation, Hackensack University Medical Center, Hackensack, NJ, USA.

Study Question: Does the upregulation of the zinc finger E-box binding homeobox 2 (ZEB2) transcription factor in human trophoblast cells lead to alterations in gene expression consistent with an epithelial-mesenchymal transition (EMT) and a consequent increase in invasiveness?

Summary Answer: Overexpression of ZEB2 results in an epithelial-mesenchymal shift in gene expression accompanied by a substantial increase in the invasive capacity of human trophoblast cells.

What Is Known Already: In-vivo results have shown that cytotrophoblast differentiation into extravillous trophoblast involves an epithelial-mesenchymal transition. The only EMT master regulatory factor which shows changes consistent with extravillous trophoblast EMT status and invasive capacity is the ZEB2 transcription factor. Read More

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http://dx.doi.org/10.1093/molehr/gay053DOI Listing
February 2019
11 Reads

Exosome-mediated intracellular signalling impacts the development of endometriosis-new avenues for endometriosis research.

Mol Hum Reprod 2019 Jan;25(1):2-4

Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia.

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http://dx.doi.org/10.1093/molehr/gay050DOI Listing
January 2019
1 Read

Phenotypic variations in transferred progeny due to genotype of surrogate mother.

Mol Hum Reprod 2019 Feb;25(2):88-99

Department of Experimental Animal Genetic Resources, Laboratory of the Genetics of Experimental Animals, Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia.

Study Question: Does the genotype of the surrogate mother modulate the body composition and immunity of her offspring?

Summary Answer: C57BL/6J (B6) progenies carried by immunodeficient NOD SCID (NS) mothers had increased adaptive but decreased innate, immune responsiveness in comparison with the same genotype offspring carried by immunocompetent mothers, B6 and BALB/c (C); the B6 progenies carried by the same genotype mothers also showed higher body fat than the others.

What Is Known Already: Differences in the major histocompatibility complex (MHC) genes between mother and foetus is considered as an important factor in prenatal embryo development, whereas the impact of such dissimilarity on the phenotype of the mature progeny is unclear.

Study Design, Size, Duration: Transplantation of two-cell mouse embryos into recipient females of the different MHC (H2) genotypes was used as an approach to simulate three variants of the immunogenic mother-foetus interaction: (i) bidirectional immunogenic dialogue between B6 (H2b haplotype) embryos and C (H2d haplotype) surrogate mother; (ii) one-way immunogenic interaction between B6 embryos and immunodeficient NS (H2g7 haplotype) surrogate mother and (iii) reduced immunogenetic dialogue between embryos and surrogate mother of the same H2b haplotype resulting in only a maternal response to HY antigens of male foetuses. Read More

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http://fdslive.oup.com/www.oup.com/pdf/production_in_progres
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http://dx.doi.org/10.1093/molehr/gay052DOI Listing
February 2019
14 Reads

MHR | driving reproductive science.

Authors:

Mol Hum Reprod 2019 Jan;25(1)

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http://dx.doi.org/10.1093/molehr/gay051DOI Listing
January 2019

Macrophages alternatively activated by endometriosis-exosomes contribute to the development of lesions in mice.

Mol Hum Reprod 2019 Jan;25(1):5-16

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, China.

Study Question: Do exosomes play a role in the pathogenesis of endometriosis in a murine model?

Summary Answer: Exosomes from endometriosis (EMS) can alternatively activate macrophages and thus contribute to the development of lesions in mice.

What Is Known Already: The pathogenesis of endometriosis, an inflammatory disease, possibly involves peritoneal macrophages. Exosomes are recognized as a new communicator among cells and a key modulator in several inflammatory diseases. Read More

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https://academic.oup.com/molehr/advance-article/doi/10.1093/
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http://dx.doi.org/10.1093/molehr/gay049DOI Listing
January 2019
10 Reads

Studying the nuts and bolts of spermatozoa.

Authors:
Allan Pacey

Mol Hum Reprod 2018 Dec;24(12):565-566

Department of Oncology and Metabolism, University of Sheffield, Level 4, The Jessop Wing, Tree Root Walk, Sheffield, UK.

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https://academic.oup.com/molehr/advance-article/doi/10.1093/
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http://dx.doi.org/10.1093/molehr/gay047DOI Listing
December 2018
8 Reads

RHOA activity in expanding blastocysts is essential to regulate HIPPO-YAP signaling and to maintain the trophectoderm-specific gene expression program in a ROCK/actin filament-independent manner.

Mol Hum Reprod 2019 Feb;25(2):43-60

Institute for Biogenesis Research, Department of Anatomy, Biochemistry and Physiology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA.

Study Question: What molecular signals are required to maintain the functional trophectoderm (TE) during blastocyst expansion of the late stage of preimplantation development?

Summary Answer: The activity of ras homology family member A (RHOA) GTPases is necessary to retain the expanded blastocyst cavity and also to sustain the gene expression program specific to TE.

What Is Known Already: At the early stages of preimplantation development, the precursor of the TE lineage is generated through the molecular signals that integrate RHOA, RHO-associated coiled-coil containing protein kinase (ROCK), the apicobasal cell polarity, and the HIPPO-Yes-associated protein (YAP) signaling pathway. By contrast, molecular mechanisms regulating the maintenance of the TE characteristics at the later stage, which is crucial for blastocyst hatching and implantation, are scarcely understood. Read More

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https://academic.oup.com/molehr/advance-article/doi/10.1093/
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http://dx.doi.org/10.1093/molehr/gay048DOI Listing
February 2019
5 Reads

Enhanced expression of TACE contributes to elevated levels of sVCAM-1 in endometriosis.

Mol Hum Reprod 2019 Feb;25(2):76-87

Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria.

Study Question: Are increased sVCAM-1 and sICAM-1 levels associated with tumor necrosis factor-alpha-converting enzyme (TACE) activity in endometriosis?

Summary Answer: Here we provide the first functional evidence that induced TACE activity in human endometriotic epithelial cells is at least in part responsible for the enhanced release of sVCAM-1 from these cells.

What Is Known Already: We and others have shown that serum-soluble (s)VCAM-1 levels are significantly higher in women with endometriosis, compared to disease-free controls. Experimental evidence exists suggesting a role of sICAM-1 and sVCAM-1 in the pathogenesis of endometriosis. Read More

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https://academic.oup.com/molehr/advance-article/doi/10.1093/
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http://dx.doi.org/10.1093/molehr/gay042DOI Listing
February 2019
12 Reads

Probing human sperm metabolism using 13C-magnetic resonance spectroscopy.

Mol Hum Reprod 2019 Jan;25(1):30-41

Academic Unit of Reproductive & Developmental Medicine, Department of Oncology and Metabolism, University of Sheffield, Level 4, The Jessop Wing, Tree Root Walk, Sheffield, UK.

Study Question: Can 13C-Magnetic Resonance Spectroscopy (MRS) of selected metabolites provide useful information about human sperm metabolism and how glycolysis or oxidative phosphorylation are used by different sperm populations?

Summary Answer: Sperm populations, prepared by density gradient centrifugation (DGC) and incubated with either 13Cu-glucose, 13Cu-fructose or 13C1-pyruvate, showed consistent evidence of metabolism generating principally lactate and more intermittently bicarbonate, and significantly more lactate was produced from 13Cu-glucose by vital or motile sperm recovered from the 40/80% interface compared to those from the pellet, which could not be accounted for by differences in the non-sperm cells present.

What Is Known Already: Previous studies have focused on CO2 or other specific metabolite production by human sperm and there remains considerable debate about whether glycolysis and/or oxidative phosphorylation is the more important pathway for ATP production in sperm.

Study Design, Size, Duration: Sperm populations were prepared by DGC and subjected to 13C-MRS to answer the following questions. Read More

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https://academic.oup.com/molehr/advance-article/doi/10.1093/
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http://dx.doi.org/10.1093/molehr/gay046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314230PMC
January 2019
11 Reads

MicroRNAs involved in the HMGA2 deregulation and its co-occurrence with MED12 mutation in uterine leiomyoma.

Mol Hum Reprod 2018 Nov;24(11):556-563

Department of Clinical Genetics, Vejle Hospital, Institute of Regional Health Research, University of Southern Denmark, DK, Denmark.

Study Question: Can the mediator complex subunit 12 (MED12) mutation and high mobility group AT-hook 2 (HMGA2) overexpression co-occurrence be explained by the alternative mechanism of HMGA2 dysregulation in uterine leiomyomas (UL)?

Summary Answer: The co-occurrence of MED12 mutation and HMGA2 overexpression, and a negative correlation of five validated or predicted microRNAs that target HMGA2 were reported.

What Is Known Already: The recent stratification of UL, according to recurrent and mutually exclusive genomic alterations affecting HMGA2, MED12, fumarate hydratase (FH) and collagen type IV alpha 5-alpha 6 (COL4A5-COL4A6) pointed out the involvement of distinct molecular pathways. However, the mechanisms of regulation involving these drivers are poorly explored. Read More

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https://academic.oup.com/molehr/article/24/11/556/5078567
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http://dx.doi.org/10.1093/molehr/gay037DOI Listing
November 2018
5 Reads

Down-regulation of long non-coding RNA MALAT1 inhibits granulosa cell proliferation in endometriosis by up-regulating P21 via activation of the ERK/MAPK pathway.

Mol Hum Reprod 2019 Jan;25(1):17-29

Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.

Study Question: Is there a specific mechanism underlying the association between lung adenocarcinoma transcript 1 (MALAT1) and endometriosis-related infertility?

Summary Answer: The down-regulation of MALAT1 in endometriosis granulosa cells (GCs) may have an adverse effect on the growth and development of oocytes by inhibiting GC proliferation, due to cell cycle-dependent mechanisms that enhance P21 expression through activation of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway.

What Is Known Already: The association between endometriosis and infertility is well supported throughout the literature, and endometriosis per se and its surgical treatment have an adverse effect on the ovarian reserve and on oocyte development. MALAT1, one of the most extensively expressed and evolutionarily conserved transcripts, has been implicated to play a role in human development and many diseases. Read More

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https://academic.oup.com/molehr/advance-article/doi/10.1093/
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http://dx.doi.org/10.1093/molehr/gay045DOI Listing
January 2019
5 Reads

Activation of latent transforming growth factor-β1, a conserved function for pregnancy-specific beta 1-glycoproteins.

Mol Hum Reprod 2018 Dec;24(12):602-612

Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Study Question: Do all 10 human pregnancy-specific beta 1-glycoproteins (PSGs) and murine PSG23 activate latent transforming growth factor-β1 (TGF-β1)?

Summary Answer: All human PSGs and murine PSG23 activated latent TGF-β1.

What Is Known Already: Two of the 10 members of the PSG1 family, PSG1 and PSG9, were previously shown to activate the soluble small latent complex of TGF-β1, a cytokine with potent immune suppressive functions.

Study Design, Size, Duration: Recombinant PSGs were generated and tested for their ability to activate the small latent complex of TGF-β1 in a cell-free ELISA-based assay and in a bioassay. Read More

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https://academic.oup.com/molehr/advance-article/doi/10.1093/
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http://dx.doi.org/10.1093/molehr/gay044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262632PMC
December 2018
12 Reads

Concordance between different trophectoderm biopsy sites and the inner cell mass of chromosomal composition measured with a next-generation sequencing platform.

Mol Hum Reprod 2018 Dec;24(12):593-601

Department of Obstetrics and Gynecology, National Taiwan University Hospital and College of Medicine, No. 8, Chung-Shan South Road, Taipei City, Taiwan (ROC).

Study Question: In PGS, does chromosomal constitution differ among trophectoderm (TE) biopsy sites and between them and the inner cell mass (ICM)?

Summary Answer: The ploidy concordance between ICM and TE was independent of whether the biopsy site in the TE was near to or far from the ICM.

What Is Known Already: TE biopsies are considered less harmful to developing embryos than blastomere biopsies. Removal of multi-cellular samples permits high-resolution next-generation sequencing (Veriseq NGS) to detect aneuploidy present in a minority of cells (mosaicism of diploid and aneuploid cells). Read More

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https://academic.oup.com/molehr/advance-article/doi/10.1093/
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http://dx.doi.org/10.1093/molehr/gay043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262631PMC
December 2018
9 Reads

Mammalian sperm contain two factors for calcium release and egg activation: Phospholipase C zeta and a cryptic activating factor.

Authors:
Keith T Jones

Mol Hum Reprod 2018 Oct;24(10):465-468

Faculty of Sciences, University of Adelaide, 5005, South Australia, Australia, and School of Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, UK.

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http://dx.doi.org/10.1093/molehr/gay038DOI Listing
October 2018

Age-related gene expression profiles of immature human oocytes.

Mol Hum Reprod 2018 Oct;24(10):469-477

Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.

Study Question: What is the difference between the gene expression profiles of single human germinal vesicle (GV) oocytes from women of different ages?

Summary Answer: There were no statistically significant differences in gene expression profiles of human GV oocytes from women of different ages (range: 25-43).

What Is Known Already: It is well established that reproductive capacity declines as women age, which is attributed to oocyte quality since this decline is counterbalanced in older women receiving young donor oocytes. Altered gene expression of human oocytes at different stages of development in relation to female age is one of the suggested mechanisms that could explain the decrease in oocyte quality. Read More

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http://dx.doi.org/10.1093/molehr/gay036DOI Listing
October 2018
1 Read
3.750 Impact Factor

Janus kinase JAK1 maintains the ovarian reserve of primordial follicles in the mouse ovary.

Mol Hum Reprod 2018 Nov;24(11):533-542

School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW, Australia.

Study Question: Is the Janus kinase and signal transducer and activator of transcription (JAK-STAT) signalling pathway involved in ovarian follicle development and primordial follicle activation?

Summary Answer: JAK1 is a key factor involved in the regulation of primordial follicle activation and maintenance of the ovarian reserve.

What Is Known Already: A series of integrated, intrinsic signalling pathways (including PI3K/AKT, mTOR and KITL) are responsible for regulating the ovarian reserve of non-growing primordial follicles and ultimately female fertility. The JAK-STAT signal transduction pathway is highly conserved with established roles in cell division and differentiation. Read More

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http://dx.doi.org/10.1093/molehr/gay041DOI Listing
November 2018
1 Read
3.750 Impact Factor

Transcriptional landscape changes during human embryonic stem cell derivation.

Mol Hum Reprod 2018 Nov;24(11):543-555

Ghent-Fertility and Stem cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, Ghent, Belgium.

Study Question: What are the transcriptional changes occurring during the human embryonic stem cell (hESC) derivation process, from the inner cell mass (ICM) to post-ICM intermediate stage (PICMI) to hESC stage, that have downstream effects on pluripotency states and differentiation?

Summary Answer: We reveal that although the PICMI is transcriptionally similar to the hESC profile and distinct from ICM, it exhibits upregulation of primordial germ cell (PGC) markers, dependence on leukemia inhibitory factor (LIF) signaling, upregulation of naïve pluripotency-specific signaling networks and appears to be an intermediate switching point from naïve to primed pluripotency.

What Is Known Already: It is currently known that the PICMI exhibits markers of early and late-epiblast stage. It is suggested that hESCs acquire primed pluripotency features due to the upregulation of post-implantation genes in the PICMI which renders them predisposed towards differentiation cues. Read More

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https://academic.oup.com/molehr/advance-article/doi/10.1093/
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http://dx.doi.org/10.1093/molehr/gay039DOI Listing
November 2018
24 Reads

The functional anatomy of the human spermatozoon: relating ultrastructure and function.

Authors:
David Mortimer

Mol Hum Reprod 2018 Dec;24(12):567-592

Oozoa Biomedical Inc., Caulfeild Village, West Vancouver, BC, Canada.

The Internet, magazine articles, and even biomedical journal articles, are full of cartoons of spermatozoa that bear minimal resemblance to real spermatozoa, especially human spermatozoa, and this had led to many misconceptions about what spermatozoa look like and how they are constituted. This review summarizes the historical and current state of knowledge of mammalian sperm ultrastructure, with particular emphasis on and relevance to human spermatozoa, combining information obtained from a variety of electron microscopic (EM) techniques. Available information on the composition and configuration of the various ultrastructural components of the spermatozoon has been related to their mechanistic purpose and roles in the primary aspects of sperm function and fertilization: motility, hyperactivation, capacitation, the acrosome reaction and sperm-oocyte fusion. Read More

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http://dx.doi.org/10.1093/molehr/gay040DOI Listing
December 2018
1 Read

Does the molecular and metabolic profile of human granulosa cells correlate with oocyte fate? New insights by Fourier transform infrared microspectroscopy analysis.

Mol Hum Reprod 2018 Nov;24(11):521-532

9.baby, Family and Fertility Center, Via Dante, 15, Bologna, Italy.

Study Question: Does the molecular and metabolic profile of human mural granulosa cells (GCs) correlate with oocyte fate?

Summary Answer: A close relation between the metabolic profile of mural GCs and the fate of the corresponding oocyte was revealed by the analysis of selected biomarkers defined by GC Fourier transform infrared microspectroscopy (FTIRM) analysis.

What Is Known Already: In ART, oocyte selection is mainly based on the subjective observation of its morphological features; despite recent efforts, the success rate of this practice is still unsatisfactory. FTIRM is a well-established vibrational technique recently applied to evaluate oocytes quality in several experimental models, including human. Read More

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http://dx.doi.org/10.1093/molehr/gay035DOI Listing
November 2018
9 Reads

ADAM8 localizes to extravillous trophoblasts within the maternal-fetal interface and potentiates trophoblast cell line migration through a β1 integrin-mediated mechanism.

Mol Hum Reprod 2018 Oct;24(10):495-509

British Columbia Children's Hospital Research Institute, 950 West 28th Ave, Vancouver, Canada.

Study Question: Does A Disintegrin And Metalloproteinase 8 (ADAM8) control extravillous trophoblast (EVT) differentiation and migration in early human placental development?

Summary Answer: ADAM8 mRNA preferentially localizes to invasive HLA-G-positive trophoblasts, associates with the acquirement of an EVT phenotype and promotes trophoblast migration through a mechanism requiring β1-integrin.

What Is Known Already: Placental establishment in the first trimester of pregnancy requires the differentiation of progenitor trophoblasts into invasive EVTs that produce a diverse repertoire of proteases that facilitate matrix remodeling and activation of signaling pathways important in controlling cell migration. While multiple ADAM proteases, including ADAM8, are highly expressed by invasive trophoblasts, the role of ADAM8 in controlling EVT-related processes is unknown. Read More

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http://dx.doi.org/10.1093/molehr/gay034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154767PMC
October 2018
1 Read

Transcriptome analysis of rhesus monkey failed-to-mature oocytes: deficiencies in transcriptional regulation and cytoplasmic maturation of the oocyte mRNA population.

Mol Hum Reprod 2018 Oct;24(10):478-494

Department of Animal Science and Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, MI, USA.

Study Question: Which different pathways and functions are altered in rhesus monkey oocytes that fail to mature after an ovulatory stimulus?

Summary Answer: Failed to mature (FTM) oocytes complete a large portion of the transition in transcriptome composition associated with normal maturation, but also manifest numerous differences that indicate incomplete transcriptional repression and cytoplasmic maturation affecting multiple processes.

What Is Known Already: Oocyte maturation defects contribute to unexplained female infertility. Failure of some oocytes to undergo germinal vesicle breakdown or progress to second meiotic metaphase in response to an ovulatory stimulus can limit the number of high quality oocytes available for ART. Read More

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http://dx.doi.org/10.1093/molehr/gay032DOI Listing
October 2018
4 Reads

Piezo1 channels are mechanosensors in human fetoplacental endothelial cells.

Mol Hum Reprod 2018 Oct;24(10):510-520

Leeds Institute of Cardiovascular and Metabolic Medicine, LIGHT Laboratories, University of Leeds, 6 Clarendon Way, Leeds, UK.

Study Question: Does the shear stress sensing ion channel subunit Piezo1 have an important mechanotransduction role in human fetoplacental endothelium?

Summary Answer: Piezo1 is present and functionally active in human fetoplacental endothelial cells, and disruption of Piezo1 prevents the normal response to shear stress.

What Is Known Already: Shear stress is an important stimulus for maturation and function of placental vasculature but the molecular mechanisms by which the force is detected and transduced are unclear. Piezo1 channels are Ca2+-permeable non-selective cationic channels which are critical for shear stress sensing and maturation of murine embryonic vasculature. Read More

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http://dx.doi.org/10.1093/molehr/gay033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311101PMC
October 2018

A Dolce & Gabbana model in every ART clinic?

Mol Hum Reprod 2018 Sep;24(9):431-432

Reproductive and Developmental Biology, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.

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http://dx.doi.org/10.1093/molehr/gay030DOI Listing
September 2018

Regulation of the human placental (pro)renin receptor-prorenin-angiotensin system by microRNAs.

Mol Hum Reprod 2018 Sep;24(9):453-464

School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia.

Study Question: Are any microRNAs (miRNAs) that target the placental renin-angiotensin system (RAS) in the human placenta suppressed in early gestation?

Summary Answer: Overall, 21 miRNAs with predicted RAS mRNA targets were less abundant in early versus term placentae and nine were more highly expressed.

What Is Known Already: Regulation of human placental RAS expression could alter placental development and therefore normal pregnancy outcome. The expression of genes encoding prorenin (REN), angiotensinogen, (pro)renin receptor, angiotensin converting enzyme 2, and the angiotensin II type 1 receptor are highest in early gestation, at a time when oxygen tension is at its lowest. Read More

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http://dx.doi.org/10.1093/molehr/gay031DOI Listing
September 2018
3 Reads

A novel transcriptional network for the androgen receptor in human epididymis epithelial cells.

Mol Hum Reprod 2018 Sep;24(9):433-443

Human Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL, USA.

Study Question: What is the transcriptional network governed by the androgen receptor (AR) in human epididymis epithelial (HEE) cells from the caput region and if the network is tissue-specific, how is this achieved?

Summary Answer: About 200 genes are differentially expressed in the caput HEE cells after AR activation; the AR transcriptional network is tissue-specific and may be mediated in part by distinct AR co-factors including CAAT-enhancer binding protein beta (CEBPB) and runt-related transcription factor 1 (RUNX1).

What Is Known Already: Little is known about the AR transcriptional program genome wide in HEE cells, nor its co-factors in those cells. AR has been best studied in the prostate gland epithelium and prostate cancer cell lines, due to the important role of this factor in prostate cancer. Read More

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http://dx.doi.org/10.1093/molehr/gay029DOI Listing
September 2018
5 Reads

Education, education, education-now more than ever?

Mol Hum Reprod 2018 Aug;24(8):426-429

Reproductive and Developmental Biology, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.

The generation of scientists and physicians that took part in starting the whole era of modern-assisted reproduction is currently close to retirement or has already left research. A new generation is about to take over and the profession is facing a massive transgenerational transition. Since current treatments have reached a plateau in success rates and costs, new research and development is required to further advance the field. Read More

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http://dx.doi.org/10.1093/molehr/gay028DOI Listing
August 2018
13 Reads

IGF2-derived miR-483-3p contributes to macrosomia through regulating trophoblast proliferation by targeting RB1CC1.

Mol Hum Reprod 2018 Sep;24(9):444-452

State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.

Study Question: What is the role of insulin-like growth factor 2 (IGF2)-derived miR-483-3p in macrosomia?

Summary Answer: IGF2-derived intronic miR-483-3p is overexpressed in macrosomia placentas, and miR-483-3p prompts HTR-8/SVneo extravillous trophoblast cell line proliferation through down-regulation of its target RB1 inducible coiled-coil 1 (RB1CC1).

What Is Known Already: Macrosomia is a common pregnancy-associated disease and causes a number of adverse maternal and perinatal outcomes. The development of macrosomia is reportedly attributable to over proliferation of the placental cells. Read More

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http://dx.doi.org/10.1093/molehr/gay027DOI Listing
September 2018
12 Reads

Heterogeneous nuclear ribonucleoprotein C1 may control miR-30d levels in endometrial exosomes affecting early embryo implantation.

Mol Hum Reprod 2018 Aug;24(8):411-425

Department of Obstetrics and Gynecology, School of Medicine, Stanford University, CA, USA.

Study Question: Is there a specific mechanism to load the microRNA (miRNA), hsa-miR-30d, into exosomes to facilitate maternal communication with preimplantation embryos?

Summary Answer: The heterogeneous nuclear ribonucleoprotein C1 (hnRNPC1) is involved in the internalization of endometrial miR-30d into exosomes to prepare for its subsequent incorporation into trophectoderm cells.

What Is Known Already: Our group previously described a novel cell-to-cell communication mechanism involving the delivery of endometrial miRNAs from the maternal endometrium to the trophectoderm cells of preimplantation embryos. Specifically, human endometrial miR-30d is taken up by murine blastocysts causing the overexpression of certain genes involved in embryonic adhesion (Itb3, Itga7 and Cdh5) increasing embryo adhesion rates. Read More

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http://dx.doi.org/10.1093/molehr/gay026DOI Listing
August 2018
5 Reads

Expression of adhesion and extracellular matrix genes in human blastocysts upon attachment in a 2D co-culture system.

Mol Hum Reprod 2018 07;24(7):375-387

Research Group Reproduction and Immunology, Vrije Universiteit Brussel, Brussels, Belgium.

Study Question: What are the changes in human embryos, in terms of morphology and gene expression, upon attachment to endometrial epithelial cells?

Summary Answer: Apposition and adhesion of human blastocysts to endometrial epithelial cells are predominantly initiated at the embryonic pole and these steps are associated with changes in expression of adhesion and extracellular matrix (ECM) genes in the embryo.

What Is Known Already: Both human and murine embryos have been co-cultured with Ishikawa cells, although embryonic gene expression associated with attachment has not yet been investigated in an in vitro implantation model.

Study Design, Size, Duration: Vitrified human blastocysts were warmed and co-cultured for up to 48 h with Ishikawa cells, a model cell line for receptive endometrial epithelium. Read More

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http://dx.doi.org/10.1093/molehr/gay024DOI Listing

Characterization of a non-human primate model for the study of testicular peritubular cells-comparison with human testicular peritubular cells.

Mol Hum Reprod 2018 Aug;24(8):401-410

Cell Biology-Anatomy III, Biomedical Center Munich (BMC), Ludwig-Maximilians-Universität München, Großhaderner Strasse 9, Martinsried, Germany.

Study Question: Are monkey testicular peritubular cells (MKTPCs) from the common marmoset monkey (Callithrix jacchus) a suitable translational model for the study of human testicular peritubular cells (HTPCs)?

Summary Answer: MKTPCs can be isolated and propagated in vitro, retain characteristic markers for testicular peritubular cells and their proteome strongly (correlation coefficient of 0.78) overlaps with the proteome of HTPCs.

What Is Known Already: Smooth-muscle-like peritubular cells form the wall of seminiferous tubules, transport sperm, are immunologically active, secrete a plethora of factors and may contribute to the spermatogonial stem cell niche. Read More

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http://dx.doi.org/10.1093/molehr/gay025DOI Listing
August 2018
7 Reads

A novel mouse model of testicular granulosa cell tumors.

Mol Hum Reprod 2018 07;24(7):343-356

Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA.

Study Question: What is the role of dysregulated transforming growth factor beta (TGFB) signaling in the development of sex cord-stromal tumors in the testis?

Summary Answer: Overactivation of TGFB signaling results in the development of testicular tumors resembling granulosa cell tumors (GrCTs).

What Is Known Already: In an earlier study, we demonstrated that constitutively active TGFB receptor 1 (TGFBR1) in ovarian somatic cells promotes the development of ovarian GrCTs. However, the consequence of dysregulation of TGFB signaling in the pathobiology of the testis, remains poorly defined. Read More

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http://dx.doi.org/10.1093/molehr/gay023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279300PMC
July 2018
6 Reads

Building tomorrow's in vitro-derived germ cells on today's solid facts.

Authors:
Michele Boiani

Mol Hum Reprod 2018 07;24(7):341-342

Max-Planck-Institute for Molecular Biomedicine, Röntgenstraße 20, Münster, Germany.

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http://dx.doi.org/10.1093/molehr/gay022DOI Listing

Retrospective analysis: reproducibility of interblastomere differences of mRNA expression in 2-cell stage mouse embryos is remarkably poor due to combinatorial mechanisms of blastomere diversification.

Mol Hum Reprod 2018 07;24(7):388-400

Max Planck Institute for Molecular Biomedicine, Roentgenstrasse 20, Muenster, Germany.

Study Question: What is the prevalence, reproducibility and biological significance of transcriptomic differences between sister blastomeres of the mouse 2-cell embryo?

Summary Answer: Sister 2-cell stage blastomeres are distinguishable from each other by mRNA analysis, attesting to the fact that differentiation starts mostly early in the mouse embryo; however, the interblastomere differences are poorly reproducible and invoke the combinatorial effects of known and new mechanisms of blastomere diversification.

What Is Known Already: Transcriptomic datasets for single blastomeres in mice have been available for years but have never been systematically analysed together, although such an analysis may shed light onto some unclarified topics of early mammalian development. Two unknowns that remain are at which stage embryonic blastomeres start to diversify from each other and what is the molecular origin of that difference. Read More

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http://dx.doi.org/10.1093/molehr/gay021DOI Listing
July 2018
1 Read

Expression of GRIM-19 in unexplained recurrent spontaneous abortion and possible pathogenesis.

Mol Hum Reprod 2018 07;24(7):366-374

Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, PR China.

Study Question: Is aberrant expression of gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) associated with unexplained recurrent spontaneous abortion (URSA)?

Summary Answer: GRIM-19 deficiency may regulate regulatory T cell/T helper 17 cell (Treg/Th17) balance partly through reactive oxygen species (ROS)-mammalian target of rapamycin (mTOR) signaling axis in URSA.

What Is Known Already: Immunological disorders may cause impaired maternal immune tolerance to the fetus and result in fetal rejection. The differentiation of Treg and Th17 cells is controlled by phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling pathway. Read More

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http://dx.doi.org/10.1093/molehr/gay020DOI Listing
July 2018
1 Read

Exosomal miR-214 from endometrial stromal cells inhibits endometriosis fibrosis.

Mol Hum Reprod 2018 07;24(7):357-365

Beijing Obstetrics and Gynecology Hospital, Capital Medical University, No. 251, Yaojiayuan Road, Chaoyang District, Beijing, China.

Study Question: Is it possible to improve fibrosis in endometriosis by microRNA-214 delivery in exosomes?

Summary Answer: Upregulation of miR-214 may inhibit fibrogenesis and its delivery by exosomes derived from ectopic endometrial stromal cells (ESCs), offers an alternative therapeutic approach for endometriosis fibrosis.

What Is Known Already: Fibrosis is the primary pathological feature of endometriosis. MiR-214 plays an important role in fibrotic disease. Read More

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http://dx.doi.org/10.1093/molehr/gay019DOI Listing
July 2018
3 Reads
3.750 Impact Factor

Spermatogonial behavior in marmoset: a new generation, their kinetics and niche.

Mol Hum Reprod 2018 06;24(6):299-309

Laboratório de Biologia Estrutural e Reprodução, Departamento de Morfologia, Instituto de Ciências Biológicas-ICB, Universidade Federal de Minas Gerais-UFMG, 31.270-901 Belo Horizonte, MG, Brazil.

Study Question: Could a more detailed evaluation of marmoset spermatogonial morphology, kinetics and niches using high-resolution light microscopy (HRLM) lead to new findings?

Summary Answer: Three subtypes of marmoset undifferentiated spermatogonia, which were not evenly distributed in terms of number and position along the basal membrane, and an extra premeiotic cell division not present in humans were identified using HRLM.

What Is Known Already: The seminiferous epithelium cycle (SEC) of marmosets is divided into nine stages when based on the acrosome system, and several spermatogenic stages can usually be recognized within the same tubular cross-section. Three spermatogonial generations have been previously described in marmosets: types Adark, Apale and B spermatogonia. Read More

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http://dx.doi.org/10.1093/molehr/gay017DOI Listing
June 2018
2 Reads

Presence of aggregates of smooth endoplasmic reticulum in MII oocytes affects oocyte competence: molecular-based evidence.

Mol Hum Reprod 2018 06;24(6):310-317

Unit of Physiopathology of Human Reproduction, Ospedale Policlinico San Martino, Genoa, Italy.

Study Question: Does the presence of aggregates of smooth endoplasmic reticulum (SERa) impact the transcriptome of human metaphase II (MII) oocytes?.

Summary Answer: The presence of SERa alters the molecular status of human metaphase II oocytes.

What Is Known Already: Oocytes presenting SERa are considered dysmorphic. Read More

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http://dx.doi.org/10.1093/molehr/gay018DOI Listing
June 2018
2 Reads

Corrigendum: Is 8% O2 more normoxic than 21% O2 for long-term in vitro cultures of human primary term cytotrophoblasts?

Mol Hum Reprod 2018 05;24(5):283

Department of Obstetrics, IREC, Université Catholique de Louvain, Brussels, Belgium.

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http://dx.doi.org/10.1093/molehr/gay015DOI Listing
May 2018
1 Read

Not every sperm is sacred; a perspective on male infertility.

Mol Hum Reprod 2018 06;24(6):287-298

Priority Research Centre for Reproductive Science, Faculty of Science, University of Newcastle, Callaghan, New South Wales, Australia.

This article is a personal perspective on male infertility, a condition that is not only extremely prevalent but also a major reason for couples to resort to ART. The introduction of ICSI as a form of facilitated fertilization had a revolutionary impact on our capacity to treat cases of male infertility associated with severely compromised semen quality. However, the widespread use of this technique is also thought to pose risks in terms of the incidence of miscarriage, the health and wellbeing of the offspring and perpetuation of the infertile phenotype into future generations. Read More

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http://dx.doi.org/10.1093/molehr/gay010DOI Listing
June 2018
3 Reads

In vitro formation of the blood-testis barrier during long-term organotypic culture of human prepubertal tissue: comparison with a large cohort of pre/peripubertal boys.

Mol Hum Reprod 2018 05;24(5):271-282

Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, 1200 Brussels, Belgium.

Study Question: How does the formation of the blood-testis barrier (BTB), as reflected by the expression of connexin 43 and claudin 11 proteins during the pubertal transition period, take place in vitro compared to samples from a large cohort of pre/peripubertal boys?

Summary Answer: The BTB connexin 43 and claudin 11 expression patterns appeared to be partially achieved in organotypic culture when compared to that in samples from 71 pre/peripubertal patients.

What Is Known Already: Although alterations in the protein expression patterns of the BTB, whose main components are connexin 43 and claudin 11, are known to be associated with impaired spermatogenesis in mice and adult men, there is a lack of knowledge on its formation in pre-peripubertal human tissue both in vitro and in vivo. Moreover, despite Sertoli cell (SC) maturation during long-term organotypic culture of immature testicular tissue (ITT), initiation of spermatogenesis has not yet been achieved. Read More

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http://dx.doi.org/10.1093/molehr/gay012DOI Listing
May 2018
1 Read

Advanced glycation end products alter steroidogenic gene expression by granulosa cells: an effect partially reversible by vitamin D.

Mol Hum Reprod 2018 06;24(6):318-326

Department of Neurological Sciences and Obstetrics, Gynecology and Reproductive Sciences, University of Vermont College of Medicine, 111 Colchester Ave, Burlington, VT 05401, USA.

Study Question: Does vitamin D attenuate the adverse effects of advanced glycation end products (AGEs) on steroidogenesis by human granulosa cells (GCs)?

Summary Answer: AGEs alter the expression of genes important in steroidogenesis while 1,25-dihydroxyvitamin D3 (vit D3) in vitro attenuates some of the actions of AGEs on steroidogenic gene expression, possibly by downregulating the expression of the pro-inflammatory cell membrane receptor for AGEs (RAGE).

What Is Known Already: Vitamin D attenuates the pro-inflammatory effects of AGEs in non-ovarian tissues.

Study Design, Size, Duration: Women who were undergoing IVF were enrolled. Read More

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http://dx.doi.org/10.1093/molehr/gay014DOI Listing
June 2018
4 Reads

Critical role of mTOR, PPARγ and PPARδ signaling in regulating early pregnancy decidual function, embryo viability and feto-placental growth.

Mol Hum Reprod 2018 06;24(6):327-340

Universidad de Buenos Aires, Facultad de Medicina, Paraguay 2155, Buenos Aires, Argentina.

Study Question: What are the consequences of inhibiting mTOR, the mechanistic target of rapamycin (mTOR), and the peroxisome proliferator activated receptor gamma (PPARγ) and PPARδ pathways in the early post-implantation period on decidual function, embryo viability and feto-placental growth in the rat?

Summary Answer: mTOR inhibition from Days 7 to 9 of pregnancy in rats caused decidual PPARγ and PPARδ upregulation on Day 9 of pregnancy and resulted in embryo resorption by Day 14 of pregnancy. PPARγ and PPARδ inhibition differentially affected decidual mTOR signaling and levels of target proteins relevant to lipid histotrophic nutrition and led to reduced feto-placental weights on Day 14 of pregnancy.

What Is Known Already: Although mTOR, PPARγ and PPARδ are nutrient sensors important during implantation, the role of these signaling pathways in decidual function and how they interact in the early post-implantation period are unknown. Read More

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http://dx.doi.org/10.1093/molehr/gay013DOI Listing
June 2018
3 Reads