Mouse pre-implantation development gives rise to the blastocyst, which is made up of at least three distinct cell types: trophectoderm (TE) that surrounds a cavity, and an inner mass (ICM) comprising primitive endoderm (PE) epiblast (EPI). However, underlying mechanisms involved in patterning cleavage-stage embryo are still unresolved. By analyzing distribution transcription factors Oct4 (Pou5f1), Cdx2 Nanog precisely defined stages development, we were able identify critical events leading...

Hedgehog signaling is required for formation and patterning of the anterior pituitary gland. However, role in precursor cell specification subsequent placode not well understood. We analyzed lineages find that pitx3 distal-less3b (dlx3b) expression domains define lens positions. show pre-placode specification, whereas dlx3b dlx4b are to restrict size. In smoothened mutant embryos cannot transduce signals, median precursors mis-specified form an ectopic lens. Moreover, overexpression sonic...

To improve clinical outcomes of human medically assisted reproduction, the transfer multiple embryos is frequently performed. This leads to high rates pregnancies. In this study we explored if a cohort patients can be defined, that benefits from two while mitigating odds pregnancy by considering female patients’ age, embryo quality and quality. retrospective rate (CPR), live birth (LBR) (MPR) after fresh single transfers (SET, n = 245) were compared those double (DET, 278). Female patient’s...

The Fragile X mental retardation type 1 gene (FMR1) contains a CGG triplet cluster of varied length (30 repeats on average) located in its 5′ UTR. In premutated state (54–200 repeats), FMR1 contributes to the pathogenesis premature ovarian insufficiency (POI). Its gray zone alleles (41–54 repeats) are supposed impair function as well. case repeat > 200, syndrome occurs. Post-transcriptional expression is regulated by microRNAs. Although miR-323a-3p overexpression suppresses various...

Knowledge about the mechanism that establishes embryonic polarity is fundamental in understanding mammalian development. In re-addressing several controversial claims, we recently proposed a model which mouse not specified until blastocyst stage. Before fertilization, fully differentiated oocyte has been characterized as "polarized," and indeed observed sperm preferentially enters polar body half. Here show preferential entry due to an intrinsic of oocyte, since fertilization takes place...

Fragile-X-Mental-Retardation-1- (FMR1)-gene is supposed to be a key gene for ovarian reserve and folliculogenesis. It contains in its 5'-UTR triplet-base-repeat (CGG), that varies between 26 34 general population. CGG-repeat-lengths with 55-200 repeats (pre-mutation = PM) show instable heredity tendency increase are associated premature-ovarian-insufficiency or failure (POI/POF) about 20%. FMR1-mRNA-expression leucocytes granulosa cells (GCs) increases CGG-repeat-length PM-carriers, but...

Background: The KRAB module mediates ectopic and drug-controllable transcriptional repression.Results: Targeting of to a mouse gene body results in reversible heterochromatization silencing adult embryonic cells.Conclusion: binding bodies does not induce stable DNA promoter methylation as previously thought.Significance: These proof-of-principle experiments provide the basis for development novel KRAB-based tools vivo. repression. Results: cells. Conclusion: thought. Significance:

This study attempted at identifying the main parameters influencing outcome of frozen embryo transfers.This is a single-center retrospective cohort 830 frozen-embryo-transfer cycles performed German university hospital from January 2012 to December 2016. Main were clinical pregnancy and live birth rate. Twelve patient- cycle-dependent factors analyzed in terms their influence on transfers. Multivariate logistic regression analysis was used for modelling dependency different outcomes.The rate...

Mammalian preimplantation development serves to form a blastocyst, structure that is able implant into the mother's uterus support further of embryo proper. In developing conceptus, first differentiation events separate epithelial trophectoderm from inner cell mass, which comprised primitive endoderm and embryo-generating epiblast. Although process blastocyst formation may appear simple, its morphogenesis mechanism(s) lineage specification are not yet fully understood. Here we discuss...

Development of the gonads under complex androgen regulation is critical for germ cells specification. In this work we addressed relationship between androgens and genomic integrity determining human fertility. We used different study groups: individuals with Differences Sex (DSD), including Complete Androgen Insensitivity Syndrome (CAIS) due to mutated receptor (AR), men idiopathic nonobstructive azoospermia. Both showed genome status influenced by signaling via innate immune response...

Fragile X mental retardation protein (FMRP) is a translational repressor encoded by

The aim of this study was to compare pregnancy rates in patients undergoing IVF/ICSI with embryo transfer after 4 and 5 days culture a closed incubation system integrated time-lapse imaging. Out n = 2207 vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) cycles performed between January 2011 April 2016 at tertiary referral university hospital, total 599 prolonged an (EmbryoScope© (Vitrolife)) until day or were retrospectively analyzed regard morphology rates. A on compared...

We aimed to determine whether a functional link with impact on female ovarian reserve exists between FMR1 expression and ratios of AKT/mTOR signaling genes in human granulosa cells vivo, as suggested from prior vitro data. Three hundred nine women, who were classified normal (NOR; n = 225) poor (POR; 84) responders based their reserve, recruited during stimulation for assisted reproductive techniques. Expressions key the AKT/FOXO1/3 pathways comparatively analyzed cells. NOR POR correlated...

Abstract In humans, FMR1 (fragile X mental retardation 1) is strongly expressed in granulosa cells (GCs) of the female germline and apparently controls efficiency folliculogenesis. Major control mechanism(s) gene transcription rate seem to be based on CpG-methylation along CpG island promoter. Conducting CpG-methylation-specific bisulfite-treated PCR assays subsequent sequence analyses both alleles, revealed three variably methylated domains (FMR1-VMR (variably region) 1, -2, -3) one...

Fragile X-associated primary ovarian insufficiency (FXPOI) is characterized by oligo/amenorrhea and hypergonadotropic hypogonadism caused the expansion of CGG repeat in 5′UTR X Mental Retardation 1 (FMR1). Approximately 20% women carrying an FMR1 premutation (PM) allele (55–200 repeat) develop FXPOI. Repeat Associated Non-AUG (RAN)-translation dependent on variable CGG-repeat length thought to cause FXPOI, due production a polyglycine-containing protein, FMRpolyG. Peripheral blood monocyte...

Background: The impact of controlled ovarian stimulation (COS) during medically assisted reproduction (MAR) on human embryogenesis is still unclear. Therefore, we investigated if early embryonic development affected by the type gonadotropin-releasing hormone (GnRH) analog used to prevent a premature LH surge. We compared embryo morphology and morphokinetics between GnRH agonist antagonist cycles, both involving chorionic gonadotropin (hCG)-trigger. To reduce possible confounding factors,...

Abstract Study question Is TGFß/BMP/SMAD pathway altered in women with POI and can results be detected from peripheral blood samples? Summary answer The mRNA-expression-alterations are detectable leukocytes of Premature Ovarian Insufficiency (POI) paving the way to use it as predictive tool. What is known already A proper ovarian function relies on a complex system signalling molecules including several BMP/TGFß-superfamily-members expressed ovary at different stages folliculogenesis acting...