Mammalian primordial germ cell specification.

The peri-implantation window of mammalian development is the crucial window for primordial germ cell (PGC) specification. Whereas pre-implantation dynamics are relatively conserved between species, the implantation window marks a stage of developmental divergence between key model organisms, and thus potential variance in the cell and molecular mechanisms for PGC specification. In humans, PGC specification is very difficult to study in vivo To address this, the combined use of human and nonhuman primate embryos, and stem cell-based embryo models are essential for determining the origin of PGCs, as are comparative analyses to the equivalent stages of mouse development. Understanding the origin of PGCs in the peri-implantation embryo is crucial not only for accurate modeling of this essential process using stem cells, but also in determining the role of global epigenetic reprogramming upon which sex-specific differentiation into gametes relies.

Effects of daily thermal fluctuations on the Atlantic silverside, a fish with temperature-dependent sex determination.

Temperature-dependent sex determination (TSD) occurs when the temperature during development affects gonad determination. Historically, most work on TSD in fishes was conducted under constant temperatures, yet daily fluctuating temperatures can significantly alter fish physiology and life history. Thus, we subjected the Atlantic silverside, Menidia menidia (a TSD species), to 28, 28 ± 2 and 28 ± 4°C (a high, masculinizing temperature) and quantified sex ratios and length. We found that the percentage of females increased by 60%-70% when the fish were exposed to daily fluctuating temperatures (from 10% to 16% and 17% under fluctuations).

EV-TRACK: transparent reporting and centralizing knowledge in extracellular vesicle research.

We argue that the field of extracellular vesicle (EV) biology needs more transparent reporting to facilitate interpretation and replication of experiments. To achieve this, we describe EV-TRACK, a crowdsourcing knowledgebase (http://evtrack.org) that centralizes EV biology and methodology with the goal of stimulating authors, reviewers, editors and funders to put experimental guidelines into practice.

Germline competency of human embryonic stem cells depends on eomesodermin.

In humans, germline competency and the specification of primordial germ cells (PGCs) are thought to occur in a restricted developmental window during early embryogenesis. Despite the importance of specifying the appropriate number of PGCs for human reproduction, the molecular mechanisms governing PGC formation remain largely unexplored. Here, we compared PGC-like cell (PGCLC) differentiation from 18 independently derived human embryonic stem cell (hESC) lines, and discovered that the expression of primitive streak genes were positively associated with hESC germline competency. Furthermore, we show that chemical inhibition of TGFß and WNT signaling, which are required for primitive streak formation and CRISPR/Cas9 deletion of Eomesodermin (EOMES), significantly impacts PGCLC differentiation from hESCs. Taken together, our results suggest that human PGC formation involves signaling and transcriptional programs associated with somatic germ layer induction and expression of EOMES.

Gender identity, sexual orientation and adverse sexual experiences in autistic females.

BACKGROUND: There is growing recognition that autistic females present with more diverse gender and sexual identities than their non-autistic counterparts. Likewise, autistic females are also at an increased risk of adverse sexual experiences. As higher rates of sexual victimisation are observed in individuals with diverse sexual identities in the broader population, rates of negative sexual experiences among autistic females remain unclear. This study aimed to investigate the representation of gender and sexual diversity within autistic females and examine their rates of regretted, and unwanted, sexual encounters among females with a transgender gender identity and non-heterosexual sexual orientation. METHODS: Two hundred and ninety-five females completed the Sexual Behaviour Scale-III (SBS-III) online. Self-reported gender identity and sexual orientation were compared between 134 autistic (Mage= 26.2 years, SD = 8.7) and 161 non-autistic females (Mage = 22.0 years, SD = 4.6). Differences in the prevalence of negative sexual experiences were compared across diagnosis and each gender identity and sexual orientation label. RESULTS: Autistic females were more likely to identify with a transgender gender identity (p < .05) and non-heterosexual sexual orientation (p < .007) compared to non-autistic females. Autistic homosexual females were more likely to have experienced a range of negative sexual experiences than autistic heterosexual females (OR ≥ 3.29; p < .01) and were more likely to have experienced unwanted sexual experiences than non-autistic females regardless of sexual orientation (OR ≥ 2.38; p < .05). There were no differences in rates of negative sexual experiences between autistic bisexual and both autistic heterosexual and non-autistic bisexual females. Non-autistic bisexual females (OR = 0.24; p = .018) presented with a reduced risk of regretted sexual experiences than non-autistic heterosexual peers. There were no differences in negative sexual experiences across gender identity in the autistic sample. LIMITATIONS: The use of fixed format response items may have restricted participants' abilities to provide rich responses pertaining to their sexual identities and nature of negative sexual experiences. The small number of participants who identified as transgender (n = 40) limits the reliability of results pertaining to sexual experiences across gender identity. Moreover, although multiple recruitment methods were used in this study, non-representative may bias estimates of prevalence rates. Thus, the data may not be representative of the broader population. CONCLUSIONS: Results indicate that autistic females present with greater diversity in their sexual identities than individuals without autism, with those with a homosexual sexual orientation being at greater risk of experiencing adverse sexual encounters. Findings suggest the importance of increased clinical attention to this diversity and the need to provide support to facilitate the development of a healthy sexual identity and reduce the risks identified in this study.

miRNA profiling of primate cervicovaginal lavage and extracellular vesicles reveals miR-186-5p as a potential antiretroviral factor in macrophages.

Cervicovaginal secretions, or their components collected, are referred to as cervicovaginal lavage (CVL). CVL constituents have utility as biomarkers and play protective roles in wound healing and against HIV-1 infection. However, several components of cervicovaginal fluids are less well understood, such as extracellular RNAs and their carriers, for example, extracellular vesicles (EVs). EVs comprise a wide array of double-leaflet membrane extracellular particles and range in diameter from 30 nm to over one micron. The aim of this study was to determine whether differentially regulated CVL microRNAs (miRNAs) might influence retrovirus replication. To this end, we characterized EVs and miRNAs of primate CVL during the menstrual cycle and simian immunodeficiency virus (SIV) infection of macaques. EVs were enriched by stepped ultracentrifugation, and miRNA profiles were assessed with a medium-throughput stem-loop/hydrolysis probe qPCR platform. Whereas hormone cycling was abnormal in infected subjects, EV concentration correlated with progesterone concentration in uninfected subjects. miRNAs were present predominantly in the EV-depleted CVL supernatant. Only a small number of CVL miRNAs changed during the menstrual cycle or SIV infection, for example, miR-186-5p, which was depleted in retroviral infection. This miRNA inhibited HIV replication in infected macrophages in vitro. In silico target prediction and pathway enrichment analyses shed light on the probable functions of miR-186-5p in hindering HIV infections via immunoregulation, T-cell regulation, disruption of viral pathways, etc. These results provide further evidence for the potential of EVs and small RNAs as biomarkers or effectors of disease processes in the reproductive tract.

An Extended Culture System that Supports Human Primordial Germ Cell-like Cell Survival and Initiation of DNA Methylation Erasure.

The development of an in vitro system in which human primordial germ cell-like cells (hPGCLCs) are generated from human pluripotent stem cells (hPSCs) has been invaluable to further our understanding of human primordial germ cell (hPGC) specification. However, the means to evaluate the next fundamental steps in germ cell development have not been well established. In this study we describe a two dimensional extended culture system that promotes proliferation of specified hPGCLCs, without reversion to a pluripotent state. We demonstrate that hPGCLCs in extended culture undergo partial epigenetic reprogramming, mirroring events described in hPGCs in vivo, including a genome-wide reduction in DNA methylation and maintenance of depleted H3K9me2. This extended culture system provides a new approach for expanding the number of hPGCLCs for downstream technologies, including transplantation, molecular screening, or possibly the differentiation of hPGCLCs into gametes by in vitro gametogenesis.

Characterising the Sexuality and Sexual Experiences of Autistic Females.

Current understandings of the sexuality of autistic females have been predominantly drawn from qualitative studies. This study aimed to quantitatively examine the sexual functioning of autistic females (N = 135), by comparing these to the sexual interest, behaviours, and experiences to 96 autistic males and 161 typically developing females. Autistic females reported less sexual interest, yet more experiences than autistic males. More autistic females also reported engaging in sexual behaviours that were later regretted, unwanted, or receiving unwanted sexual advances. Differences between autistic and typically developing females were significant. Results indicate that due to a mismatch between less sexual interest, yet increased sexual behaviours, autistic women are at greater risk of negative sexual experiences including victimisation and abuse than autistic men.

Socio-sexual functioning in autism spectrum disorder: A systematic review and meta-analyses of existing literature.

Socio-sexual functioning encompasses an individual's interests, behaviors, and knowledge with respect to sexual, romantic, and social aspects of life. An individual's understanding of these domains is developed through a range of informal and formal avenues of sexual health education. The current model demonstrated this and proposed that, compared to typically developing individuals, those with ASD develop socio-sexual functioning differently due to having less peer engagement, less relationship experience, more parental guidance, greater use of online materials, receive less school-based sexual health education, and more support from wellbeing services. Systematic review and meta-analysis of existing literature revealed that individuals with ASD have greater difficultly adhering to privacy norms, engage in less social behavior, are described as engaging in less appropriate sexual behavior, have greater concerns about themselves, and receive less sexual health education. Having fewer opportunities for appropriate informal and formal sexual health education leaves them at a double disadvantage from others who are receiving this information from both of these avenues. Some of the current meta-analytic results are cautioned by large l-square statistics which suggest that a degree of variance is being caused by extraneous factors. Further empirical research in this area is needed to overcome current design and sample limitations. Finally, the Sexual Behavior Scale was the most commonly utilized tool in the meta-analyzed studies, thus comprehensive evaluation of its functioning is warranted. The importance of work in this area is highlighted by the central role of social and sexual wellbeing on one's quality of life. Autism Res 2017, 10: 1823-1833. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Review of existing literature revealed that individuals with ASD have greater difficultly adhering to privacy norms, engage in less social behavior, are described as engaging in less appropriate sexual behavior, have greater concerns about themselves, and receive less sexual health education. Having fewer opportunities for appropriate informal and formal sexual health education leaves them at a double disadvantage from others who are receiving this information from both of these avenues.

Dickkopf-1 promotes hematopoietic regeneration via direct and niche-mediated mechanisms.

The role of osteolineage cells in regulating hematopoietic stem cell (HSC) regeneration following myelosuppression is not well understood. Here we show that deletion of the pro-apoptotic genes Bak and Bax in osterix (Osx, also known as Sp7 transcription factor 7)-expressing cells in mice promotes HSC regeneration and hematopoietic radioprotection following total body irradiation. These mice showed increased bone marrow (BM) levels of the protein dickkopf-1 (Dkk1), which was produced in Osx-expressing BM cells. Treatment of irradiated HSCs with Dkk1 in vitro increased the recovery of both long-term repopulating HSCs and progenitor cells, and systemic administration of Dkk1 to irradiated mice increased hematopoietic recovery and improved survival. Conversely, inducible deletion of one allele of Dkk1 in Osx-expressing cells in adult mice inhibited the recovery of BM stem and progenitor cells and of complete blood counts following irradiation. Dkk1 promoted hematopoietic regeneration via both direct effects on HSCs, in which treatment with Dkk1 decreased the levels of mitochondrial reactive oxygen species and suppressed senescence, and indirect effects on BM endothelial cells, in which treatment with Dkk1 induced epidermal growth factor (EGF) secretion. Accordingly, blockade of the EGF receptor partially abrogated Dkk1-mediated hematopoietic recovery. These data identify Dkk1 as a regulator of hematopoietic regeneration and demonstrate paracrine cross-talk between BM osteolineage cells and endothelial cells in regulating hematopoietic reconstitution following injury.