Premature recruitment of oocyte pool and increased mTOR activity in Fmr1 knockout mice and reversal of phenotype with rapamycin.

While mutations in the fragile X mental retardation-1 (FMR1) gene are associated with varying reproductive outcomes in females, the effects of a complete lack of FMR1 expression are not known. Here, we studied the ovarian and reproductive phenotypes in an Fmr1 knockout (KO) mouse model and the role of mammalian target of rapamycin (mTOR) signaling. Breeding, histologic and mTOR signaling data were obtained at multiple time points in KO and wild type (WT) mice fed a control or rapamycin (mTOR inhibitor) diet. KO mice showed an earlier decline in ovarian reserve than WT mice with an increased proportion of activated follicles. mTOR and phosphorylated S6 kinase (p-S6K) levels, a measure of downstream mTOR signaling, were elevated in the KO ovaries. Rapamycin blocked these effects in KO mice, and increased the primordial follicle pool and age of last litter in WT mice. Our data demonstrates an early decline in reproductive capacity in Fmr1 KO mice and proposes that premature recruitment of the primordial pool via altered mTOR signaling may be the mechanism. Reversal of phenotypes and protein levels in rapamycin-treated KO mice, as well as increased reproductive lifespan of rapamycin-fed WT mice, suggest the mTOR pathway as a potential therapeutic target

Heat shock protein expression during gametogenesis and embryogenesis.

When cells are subjected to various stress factors, they increase the production of a group of proteins called heat shock proteins (hsp). Heat shock proteins are highly conserved proteins present in organisms ranging from bacteria to man. Heat shock proteins enable cells to survive adverse environmental conditions by preventing protein denaturation. Thus the physiological and pathological potential of hsps is enormous and has been studied widely over the past two decades. The presence or absence of hsps influences almost every aspect of reproduction. They are among the first proteins produced during mammalian embryo development. In this report, the production of hsps in gametogenesis and early embryo development is described. It has been suggested that prolonged and asymptomatic infections trigger immunity to microbial hsp epitopes that are also expressed in man. This may be relevant for human reproduction, since many couples with fertility problems have had a previous genital tract infection. Antibodies to bacterial and human hsps are present at high titers in sera of many patients undergoing in vitro fertilization. In a mouse embryo culture model, these antibodies impaired the mouse embryo development at unique developmental stages. The gross morphology of these embryos resembled cells undergoing apoptosis. The TUNEL (terminal deoxynucleotidyl transferase-mediated X-dUTP nick end labeling) staining pattern, which is a common marker of apoptosis, revealed that embryos cultured in the presence of hsp antibodies stained TUNEL-positive more often than unexposed embryos. These data extend preexisting findings showing the detrimental effect of immune sensitization to hsps on embryo development

Prevention of noncommunicable diseases by interventions in the preconception period: A FIGO position paper for action by healthcare practitioners

With the increase in obesity prevalence among women of reproductive age globally, the risks of type 2 diabetes, gestational diabetes, pre‐eclampsia, and other conditions are rising, with detrimental effects on maternal and newborn health. The period before pregnancy is increasingly recognized as crucial for addressing weight management and reducing malnutrition (both under‐ and overnutrition) in both parents to reduce the risk of noncommunicable diseases (NCDs) in the mother as well as the passage of risk to her offspring. Healthcare practitioners, including obstetricians, gynecologists, midwives, and general practitioners, have an important role to play in supporting women in planning a pregnancy and achieving healthy nutrition and weight before pregnancy. In this position paper, the FIGO Pregnancy Obesity and Nutrition Initiative provides an overview of the evidence for preconception clinical guidelines to reduce the risk of NCDs in mothers and their offspring. It encourages healthcare practitioners to initiate a dialogue on women’s health, nutrition, and weight management before conception. While acknowledging the fundamental importance of the wider social and environmental determinants of health, this paper focuses on a simple set of recommendations for clinical practice that can be used even in short consultations. The recommendations can be contextualized based on local cultural and dietary practices as part of a system‐wide public health approach to influence the wider determinants as well as individual factors influencing preconception health

Evaluation of genome coverage and fidelity of multiple displacement amplification from single cells by SNP array

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 Mapping Array. An average coverage rate (86.2%) from single cells was obtained and the rates increased significantly when five or more cells were used as templates. Higher concordance for chromosome copy number from single cells could be achieved when the MDA amplified product was used as reference (93.1%) than when gDNA used as reference (82.8%). The present study indicates that satisfactory genome coverage can be obtained from single-cell MDA which may be used for studies where only a minute amount of genetic materials is available. Clinically, MDA coupled with SNP mapping array may provide a reliable and accurate method for chromosome copy number analysis and most likely for the detection of single-gene disorders as well

Tuning the graphene work function by electric field effect

We report variation of the work function for single and bi-layer graphene devices measured by scanning Kelvin probe microscopy (SKPM). Using the electric field effect, the work function of graphene can be adjusted as the gate voltage tunes the Fermi level across the charge neutrality point. Upon biasing the device, the surface potential map obtained by SKPM provides a reliable way to measure the contact resistance of individual electrodes contacting graphene.Comment: 11 pages and 8 figures including supplementary information, to appear in Nano Letter

Enhanced electric conductivity at ferroelectric vortex cores in BiFeO3

In many large ensembles, the property of the system as a whole cannot be understood from studying the individual entities alone ¿ these ensembles can be made up by neurons in the brain, transport users in traffic networks or data packages in the Internet. The past decade has seen important progress in our fundamental understanding of what such seemingly disparate 'complex systems' have in common; some of these advances are surveyed here

Manipulation of the follicular phase: Uterodomes and pregnancy - is there a correlation?

BACKGROUND: Manipulation of the follicular phase uterine epithelium in women undergoing infertility treatment, has not generally shown differing morphological effects on uterine epithelial characteristics using Scanning Electron Microscopy (SEM) and resultant pregnancy rates have remained suboptimal utilising these manipulations. The present study observed manipulation of the proliferative epithelium, with either 7 or 14 days of sequential oestrogen (E) therapy followed by progesterone (P) and assessed the appearance of pinopods (now called uterodomes) for their usefulness as potential implantation markers in seven women who subsequently became pregnant. Three endometrial biopsies per patient were taken during consecutive cycles: day 19 of a natural cycle - (group 1), days 11/12 of a second cycle after 7 days E then P - (group 2), and days 19/22 of a third cycle after 14 days E then P - (group 3). Embryo transfer (ET) was performed in a subsequent long treatment cycle (as per Group 3). RESULTS: Seven pregnancies resulted in seven viable births including one twins and one miscarriage. Analysis of the individual regimes showed 5 days of P treatment to have a higher correlation for uterodomes in all 3 cycles observed individually. It was also observed that all 7 women demonstrated the appearance of uterodomes in at least one of their cycles. CONCLUSIONS: We conclude that manipulation of the follicular phase by shortening the period of E exposure to 7 days, does not compromise uterine epithelial morphology and we add weight to the conclusion that uterodomes indicate a receptive endometrium for implantation

Tunable hot-carrier photodetection beyond the bandgap spectral limit

The spectral response of common optoelectronic photodetectors is restricted by a cutoff wavelength limit λ that is related to the activation energy (or bandgap) of the semiconductor structure (or material) (Δ) through the relationship λ = hc/Δ. This spectral rule dominates device design and intrinsically limits the long-wavelength response of a semiconductor photodetector. Here, we report a new, long-wavelength photodetection principle based on a hot-cold hole energy transfer mechanism that overcomes this spectral limit. Hot carriers injected into a semiconductor structure interact with cold carriers and excite them to higher energy states. This enables a very long-wavelength infrared response. In our experiments, we observe a response up to 55 μm, which is tunable by varying the degree of hot-hole injection, for a GaAs/AlGaAs sample with Δ = 0.32 eV (equivalent to 3.9 μm in wavelength)