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Fish are acutely affected by the increasing number of chemicals in the ambient water, including endocrine disruptors (EDC’s). EDCs include heavy metals such as cadmium and mercury, the polycyclic hydrocarbon benzo(a)pyrene, polychlorinated biphenyls, phthalates, carbamate and organophosphate pesticides, organochlorines, and bisphenol A. Nevertheless, certain groups of EDCs do manifest a comparatively greater effect on specific endocrine glands. The endocrine dysfunctions induced by explicitly acting EDCs include changes in fertility and in the ratio of male and female fish, classified as xenoestrogens or xenoandrogens. These EDCs result in a high prevalence of intersex condition including sex reversal. Feminization of male and masculinization of female fish pose a serious threat for fish populations, causing reduction or even breakdown of the reproductive performance of fish and of the yield of fisheries. It is now widely accepted that fish provide reliable biomarkers of early effects of EDC’s which data can be used as a warning signal for the ecosystem in general and a lever to diminish or prevent further release of effluents and discharges from anthropogenic activities.

Background As the critical tissue of the central nervous system, the brain has been found to be involved in gonad development. Previous studies have suggested that gonadal fate may be affected by the brain. Identifying brain-specific molecular changes that occur during estrodiol-17β (E2) -induced feminization is crucial to our understanding of the molecular control of sex differentiation by the brains of fish. Results In this study, the differential transcriptomic responses of the Takifugu rubripes larvae brain were compared after E2 treatment for 55 days. Our results showed that 514 genes were differentially expressed between E2-treated-XX (E-XX) and Control-XX (C-XX) T. rubripes, while 362 genes were differentially expressed between E2-treated-XY (E-XY) and Control-XY (C-XY). For example, the expression of cyp19a1b, gnrh1 and pgr was significantly up-regulated, while st, sl, tshβ, prl and pit-1, which belong to the growth hormone/prolactin family, were significantly down-regulated after E2 treatment, in both sexes. The arntl1, bhlbe, nr1d2, per1b, per3, cry1, cipc and ciart genes, which are involved in the circadian rhythm, were also found to be altered. Differentially expressed genes (DEGs), which were identified between E-XX and C-XX, were significantly enriched in neuroactive ligand-receptor interaction, arachidonic acid metabolism, cytokine-cytokine receptor interaction and the calcium signaling pathway. The DEGs that were identified between E-XY and C-XY were significantly enriched in tyrosine metabolism, phenylalanine metabolism, arachidonic acid metabolism and linoleic acid metabolism. Conclusion A number of genes and pathways were identified in the brain of E2-treated T. rubripes larvae by RNA-seq. It provided the opportunity for further study on the possible involvement of networks in the brain-pituitary-gonadal axis in sex differentiation in T. rubripes.

The choice of tactics for feminizing plastic surgery (one- or two-stage) remains an actually issue. To operate early, in the first months of a child’s life, when endocrinological stabilization is achieved, or to postpone the intervention until puberty? Despite the large number of approaches to surgical treatment, still not all results can be recognized as positive. There are complications that affect the quality of life of patients, not only of a surgical but also of a psychological nature. The advantages of one or another approach are currently impossible to prove, since this will require a prospective multicenter multidisciplinary study of long-term results with each of the approaches. Therefore, pediatric surgeons for a long time in the choice of tactics will be based on accumulated experience and logical reasoning. Given the extensive experience of multidisciplinary rehabilitation, the positive long-term results of two-stage feminization remains the preferred tactic for surgical treatment of girls with CAH. The increased risk of complications from the genitourinary system in the form of infections of the urinary tract, hematocolpos and hematometra in girls with a narrow common urogenital canal, which is inherent in virilization of 3, 4 and 5 degrees according to Prader, can be considered as a reason for an early one-stage feminizing plasty.

Sexual selection and sexual conflict play central roles in driving the evolution of male and female traits. Experimental evolution provides a powerful approach to study the operation of these forces under controlled environmental and demographic conditions, thereby allowing direct comparisons of evolutionary trajectories under different treatments, such as mating systems. Despite the rapid progress of experimental and statistical techniques that support experimental evolution studies, we still lack clear theoretical predictions on the effects of different mating systems beyond what intuition suggests. For example, polygamy (several males and females in a mating group) and polyandry (one single female and multiple males in a mating group) have each been used as treatments that elevate sexual selection on males and sexual conflict relative to monogamy. However, polygamy and polyandry manipulations sometimes produce different evolutionary outcomes, and the precise reasons why remain elusive. In addition, the softness of selection (i.e., scale of competition within each sex) is known to affect trait evolution, and is an important factor to consider in experimental design. To date, no model has specifically investigated how the softness of selection interacts with different mating systems. Here, we try to fill these gaps by generating clear and readily testable predictions. Our set of models were designed to capture the most important life cycle events in typical experimental evolution studies, and we use simulated changes of sex-specific gene expression profiles (i.e., feminization or masculinization) to quantify trait evolution under different selection schemes. We show that interactions between the softness of selection and the mating system can produce results that have been identified as counterintuitive in previous empirical work, such as polyandry producing stronger feminization than monogamy. We conclude by encouraging a stronger integration of modeling in future experimental evolution studies and pointing out remaining knowledge gaps for future theoretical work. This article is protected by copyright. All rights reserved.

Phytoestrogens (PhE) are contained in soy and some other plants; they are structurally similar to estrogens. PhE are used for substitution therapy in the menopause. However, some recent reviews concluded that no satisfactory evidence has been provided in favor of PhE efficiency against menopausal symptoms compared to placebo. Soy is used as an ingredient of infant food and other foodstuff as well as cattle fodder, so that residual PhE and their degradation products, e.g. equol, having estrogenic activity, can remain in meats. Soy protein is used in the food industry. Disorders of the reproductive system in humans under the influence of PhE are regarded to be rare and mild. There were single reports on altered gender-related behavior in children and feminization associated with soy consumption. In animals, the excessive PhE intake leads to derangements of fertility, sexual development and behavior. PhE are called modulators or disruptors of the endocrine system. There are no reasons to assume that benefits from such modulation would prevail in all soy consumers. Feminizing effects may be inconspicuous but statistically detectable in large populations.

Background: Gender-affirming surgery may be pursued by individuals experiencing gender dysphoria. Although genital and chest procedures are classified as medically necessary, facial feminization su...

Intersex has been reported regularly in wild populations of gonochoristic fish. The authors investigated the possible feminization of seahorses in a population of Hippocampus reidi in Brazil, as well as report a case of a brood pouch reduction after reproductive stimuli. The female seahorses of this population showed two kinds of morphological anomalies. The proportion of the animals affected in the study population was consistent and was uncorrelated with the sex ratio. The study indicates the changes in the sexual profile of the individual.

Background Wolbachia is an obligate intracellular maternally transmitted, gram-negative bacterium which forms a spectrum of endosymbiotic relationships from parasitism to obligatory mutualism in a wide range of arthropods and onchocercid nematodes, respectively. In arthropods Wolbachia produces reproductive manipulations such as male killing, feminization, parthenogenesis and cytoplasmic incompatibility for its propagation and provides an additional fitness benefit for the host to protect against pathogens, whilst in onchocercid nematodes, apart from the mutual metabolic dependence, this bacterium is involved in moulting, embryogenesis, growth and survival of the host. Methods This review details the molecular data of Wolbachia and its effect on host biology, immunity, ecology and evolution, reproduction, endosymbiont-based treatment and control strategies exploited for filariasis. Relevant peer-reviewed scientic papers available in various authenticated scientific data bases were considered while writing the review. Conclusions The information presented provides an overview on Wolbachia biology and its use in the control and/or treatment of vectors, onchocercid nematodes and viral diseases of medical and veterinary importance. This offers the development of new approaches for the control of a variety of vector-borne diseases. Graphical Abstract

We compared gender dysphoria (GD) patients and their same-sex siblings in terms of their 2D:4D ratios, which may reflect prenatal exposure to androgen, one of the possible etiological mechanisms underlying GD. Sixty-eight GD patients (46 Female-to-Male [FtM]; 22 Male-to-Female [MtF]), 68 siblings (46 sisters of FtMs; 22 brothers of MtFs), and 118 heterosexual controls (62 female; 56 male) were included in the study. FtMs were gynephilic and MtFs were androphilic. We found that 2D:4D ratios in the both right hand (p < .001) and the left hand (p = .003) were lower in male controls than in female controls. Regarding right hands, FtM GD patients had lower 2D:4D ratios than female controls (p < .001) but their ratios did not differ from those of their sisters or male controls. FtM GD patients had no significant difference in their left-hand 2D:4D ratios compared to their sisters or female and male controls. While there was no significant difference in right hands between FtM's sisters and male controls, left-hand 2D:4D ratios were significantly higher in FtM's sisters (p = .017). MtF GD patients had lower right-hand 2D:4D ratios than female controls (p

SUMMARY Introduction Wendler glottoplasty is a voice feminization surgical procedure designed to increase the fundamental frequency (F0) in male-to-female transsexual patients with gender dysphoria. On average, Wendler glottoplasty has the most significant effect on F0 among voice feminization surgical procedures. Case report We present the case of a young female patient with a testosterone-producing adrenocortical adenoma who underwent irreversible vocal changes secondary to virilization, which impacted her self-esteem and quality of life (QOL). Voice feminization surgery using Wendler glottoplasty was performed with significant improvement in F0 and QOL. Discussion Sex hormones have a profound impact on the voice. Increased testosterone and dihydrotestosterone are known to cause hypertrophy of the laryngeal muscles and ligaments, which leads to a drop in F0. However, women who present androphonia rarely require surgical management and improve with vocal therapy alone. Few cases of voice feminization procedures for the treatment of androphonia have been described in the literature. Our patient presented with severe masculinization of her voice with a F0 lower than the average adolescent male, which led to the requirement of surgical management. Conclusions Patients with severe androphonia that significantly affect their QOL and show no improvement after the management of the underlying pathology and intense vocal therapy are candidates for voice feminization surgeries. These procedures offer positive results both in terms of F0 and in improving patient's self-esteem and QOL.

Synthetic estrogens such as ethinylestradiol (EE2) are persistent micropollutants that are not effectively removed from wastewater by conventional treatments. These contaminants are released into waterbodies, where they disrupt endocrine systems of organisms and cause harmful effects such as feminization, infertility, reproduction problems and genital malformations. The consequences of this pollution for key marine ecosystems such as coral reefs and their associated microbiomes are underexplored. We evaluated the effects of EE2 concentrations of 100 ng L−1 and 100 µg L−1 on the coral metaorganism Mussismilia harttii. The results indicated no effects on visible bleaching or Fv/Fm ratios in the corals during a 17-day microcosm experiment. However, next-generation sequencing of 16S rDNA revealed a statistically significant effect of high EE2 concentrations on OTU richness, and shifts in specific microbial groups after treatments with or without EE2. These groups might be bioindicators of early shifts in the metaorganism composition caused by EE2 contamination.

This article analyzes the formation of visualization of hysterical insanity in art on the example of the canvas by Pierre-Andre Brouillet A Clinical Lesson at the Salpêtrière. Considering the long practice of feminization of insanity, we can conclude that Brouillet captured the phenomenon of the “Charcot regime”, exposing its discussion fields. By fixing the female pathological body in a certain place, he demonstrated two discursive tricks: how patriarchal institutions defined a woman as a being devoid of her own opinion, and how a woman “evaporated”, became an object under male power influence, demonstrating the significance of the term “phallocula- centrism” and scopophilia of the second half of the 19th century introduced by L. Irigaray. As a result, it reflected the characteristics of hysteria that allowed this disease to feminize insanity and introduce it into the visual culture of the time: mimetism, simulation, representa- tion, mimicry, cataloging, and registration. The female body became a pent-up “alphabet”, embodying the idea of Sigmund Freud’s mirror and Jacques Lacan’s reasoning about the nature of the hysterical personality type. The disease, which has “thousands of guises” and exists solely due to visual appearance, revealed not only the problems of Patriarchy of most social and power institutions, but also relationships. As a result, the acute and controversial colloquial characterization of “hysterical”, which was included due to the popularity of the visual image of a mentally ill woman created at the Salpêtrière, is still becoming a relevant topic for research in modern visual practices.

This study investigated the effect of 17 β‐oestradiol (E2) and 17 α‐ethinyloestradiol (EE2) on the feminization of barramundi (Lates calcarifer). Fish were fed pellets containing 10 mg E2/kg food, 20 mg E2/kg food, 5 mg EE2/kg food and 10 mg EE2/kg food from 30 to 160 days post hatch (dph), which covers the period of initial male gonad differentiation. The effect of E2 and EE2 treatment on gonadal morphology and dmrt1 and cyp19a1a gene expression was analysed by histology and RT‐qPCR. Orally delivered E2 and EE2 induced observable changes in gonad morphology. Previtellogenic oocytes (PO) were observed in 33% and 50% of the fish fed with 20 mg E2/kg at 160 dph and 12 months post hatch (mph), respectively, while PO were not observed in control fish. 10 mg E2/kg treatment did not induce feminization, but significantly suppressed testicular development. Treatment with EE2 resulted in fibrosis within gonad tissues at a dose‐dependent rate. E2 administration resulted in upregulation of the gene cyp19a1a and downregulation of dmrt1. EE2 significantly suppressed expression of dmrt1 at 160 dph and 12 mph, while cyp19a1a was not significantly different at 160 dph and was significantly downregulated at 12 mph. The result of this study showed that E2 is a more suitable hormone than EE2 to induce precocious feminization of barramundi, and when delivered through the feed it has a dose‐dependent feminizing effect.

Introduction. Single-stage feminization genitoplasty under the age of 12 months is recommended by the international consensus on the treatment of girls with congenital adrenal hyperplasia (CAH).The study objective is to evaluate the results of feminization plasty of the external genitals in infancy.Materials and methods. The single-stage feminization genitoplasty results is performed in 11 patients from 6 to 18 months age old with various forms of CAH. The single-stage feminization surgery included clitoroplasty with preservation of the head, dorsal neurovascular bundle, labioplasty and various forms of introitoplasty depending on the level of hypospadias.Results. Recurrence of hypospadias and urethro-vaginal fistula were obtained in 3 (36 %) girls. Given the structural features of the small pelvis in girls at infancy and early age, a good result of single-stage feminization genitoplasty is possible when using an apron-shaped mucous flap with mild and middle hypospadias and urogenital mobilization with severe hypospadias in combination with prolonged glucoand mineralocorticoid compensation of CAH.Conclusion. Indications for single-stage feminization genitoplasty, given the large percentage of complications, should be placed with extreme caution. Surgical intervention is justified in case of recurrent urinary tract infection and dysfunctional urination.The authors declare no conflict of interest.There is given the parental informed consent to the children’s participation in the study.

There is increasing concern about feminization of sea turtle populations resulting from female-biased production of hatchlings due to climate change and selective loss of males from other anthropogenic drivers. Extreme female-biased breeding populations would reduce the likelihood of successful mating and potentially result in high rates of infertile eggs. Infertile eggs are those in which none of the events between sperm penetration of the ovum and syngamy have occurred. Distinguishing between fertile and infertile eggs is challenging, especially in field conditions, and researchers often have relied on physical evidence gathered from unhatched eggs at the end of the incubation period, which likely have experienced tissue decomposition. We argue that infertility in sea turtle eggs can be demonstrated only by the absence of holes caused by sperm penetration of the inner perivitelline membrane; sperm bound between the inner and outer perivitelline membranes; nuclei in the blastodisc; embryonic tissue or membranes in egg contents; and/or the characteristic white spot on the egg exterior. Unhatched eggs can be examined at the end of the incubation period, but we recommend that studies specifically investigating infertility examine at least 20 oviposited eggs each from clutches laid by at least 20 different turtles at the peak of the nesting season.

Voice feminization for transgender women is a highly complicated comprehensive transition process. Voice feminization has been thought to be equal to pitch elevation. Thus, many surgical procedures have only focused on pitch raising for voice feminization. However, voice feminization should not only consider voice pitch but also consider gender differences in physical, neurophysiological, and acoustical characteristics of voice. That is why voice therapy has been the preferred choice for the feminization of the voice. Considering gender difference of phonatory system, the method for voice feminization consists of changing the following four critical elements: fundamental frequency, resonance frequency related to vocal tract volume and length, formant tuning, and phonatory pattern. Voice feminizing process can be generally divided into non-surgical feminization and surgical feminization. As a non-surgical procedure, feminization voice therapy consists of increasing fundamental frequency, improving oral and pharyngeal resonance, and behavioral therapy. Surgical feminization usually can be achieved by external approach or endoscopic approach. Based on three factors (length, tension and mass) of vocal fold for pitch modulation, surgical procedure can be classified as one-factor, two-factors and three-factors modification of vocal folds. Recent systematic reviews and meta-analysis studies have reported positive outcomes for both the voice therapy and voice feminization surgery. The benefits of voice therapy, as it is highly satisfactory, mostly increase vocal pitch, and are noninvasive. However, the surgical voice feminization of three-factors modification of vocal folds is also highly competent and provides a maximum absolute increase in vocal pitch. Voice feminization is a long transition journey for physical, neurophysiological, and psychosomatic changes that convert a male phonatory system to a female phonatory system. Therefore, strategies for voice feminization should be individualized according to the individual's physical condition, the desired change in voice pitch, economic conditions, and social roles.

Gender-affirming surgery is a group of surgical procedures that alters the physical appearance of a transgender person to resemble that socially associated with their identified gender. Masculinization and feminization surgeries include chest and breast surgery as well as genital reconstruction. The genital reconstruction surgeries have unique anatomic imaging features and are associated with complications that may require radiologic evaluation. This review provides a review of the imaging anatomy, expected findings, and complications associated with gender-affirming surgeries.

Contamination of waters, soils, sediments and other environmental media by steroid estrogens is an emerging health issue because estrogens exhibit toxic effects on fishes and animals. Levels of steroid estrogens vary widely, ranging from below the detection limit to hundreds of nanograms per liter. Estrogens alter hormone levels and the homeostasis system of living organisms, they increase the risk of cardiovascular diseases, prostate cancer and breast cancer in humans and they may induce reproductive disorders, fetal malformations and feminization of males. Here, we review detection methods of steroid estrogens in water samples. Methods mainly include chemical analysis, immunoassays and bioassays. Advanced sensors increase the selectivity and sensitivity of electrochemical assays. For instance, graphene-based sensors can decrease the detection limit to 50 fM, though estrogen analogues may interfere. Immunoassays such as ELISA have the advantages of high sensitivity, fast analysis speed and wide applicability from 2 to 4000 ng/L, though it is susceptible to cross-reactivity.

Anti-Müllerian hormone (Amh, or Müllerian-inhibiting substance, Mis), a member of TGF-β superfamily, has been well documented in some vertebrates as initiator or key regulator in sexual development, and particularly in fish. However, its functional role has not yet been identified in reptiles. Here, we characterized the Amh gene in the Chinese soft-shelled turtle Pelodiscus sinensis, a typical reptilian species exhibiting ZZ/ZW sex chromosomes. The messenger RNA of Amh was initially expressed in male embryonic gonads by stage 15, preceding gonadal sex differentiation, and exhibited a male-specific expression pattern throughout embryogenesis. Moreover, Amh was rapidly upregulated during female-to-male sex reversal induced by aromatase inhibitor letrozole. Most importantly, Amh loss of function by RNA interference led to complete feminization of genetic male (ZZ) gonads, suppression of the testicular marker Sox9, and upregulation of the ovarian regulator Cyp19a1. Conversely, overexpression of Amh in ZW embryos resulted in female-to-male sex reversal, characterized by the formation of a testis structure, ectopic activation of Sox9, and a remarkable decline in Cyp19a1. Collectively, these findings provide the first solid evidence that Amh is both necessary and sufficient to drive testicular development in a reptilian species, P. sinensis, highlighting the significance of the TGF-β pathway in reptilian sex determination.

The text is devoted to women’s presence in the Polish higher education in 1918-2018. Its history is presented in chronological-thematic order, including information about the beginnings of women’s studies at universities as well as their basic political, economic and cultural conditioning. Although during the discussed period, basis of political system in Poland changed three times, there was a constant development of the size of higher education, as well as an increase of women’s participation among students and academic faculty. The beginnings were very modest. However, today women constitute already the majority of students of higher education and almost a half of academic employees. Women, during their fight for equality in access to studies and academic career, had to overcome many legal obstacles, also informal ones, resulting from vitality of the image of traditional social role of women. Even though, the formal equality was gradually earned, it is still more difficult for women than for men to undertake studies at some faculties, and to get higher degrees and academic positions as fast as men.

Gain of alternative splicing gives rise to functional diversity in proteins and underlies the complexity and diversity of biological aspects. However, it is still not fully understood how alternatively spliced genes develop the functional novelty. To this end, we infer the evolutionary history of the doublesex gene, the key transcriptional factor in the sexual differentiation of arthropods. doublesex is controlled by sex-specific splicing and promotes both male and female differentiation in some holometabolan insects. In contrast, doublesex promotes only male differentiation in some hemimetabolan insects. Here, we investigate ancestral states of doublesex using Thermobia domestica belonging to Zygentoma, the sister group of winged insects. We find that doublesex of T. domestica expresses sex-specific isoforms but is only necessary for male differentiation of sexual morphology. This result ensures the hypothesis that doublesex was initially only used to promote male differentiation during insect evolution. However, T. domestica doublesex has a short female-specific region and upregulates the expression of vitellogenin homologs in females, suggesting that doublesex may have already controlled some aspects of feminization in the common ancestor of winged insects. Reconstruction of the ancestral sequence and prediction of the protein structure show that the female-specific isoform of doublesex has a long C-terminal disordered region in holometabolan insects, but not in non-holometabolan species. We propose that doublesex acquired a female-specific isoform and then underwent a change in the protein motif structure, which became essential for female differentiation in sexual dimorphisms.

Projected climate change is forecasted to have significant effects on biological systems worldwide. Marine turtles in particular may be vulnerable, as the sex of their offspring is determined by their incubating temperature, termed temperature-dependent sex determination. This study aimed to estimate historical, and forecast future, primary sex ratios of hawksbill turtleEretmochelys imbricatahatchlings at an important nesting ground in northeastern Qatar. Incubation temperatures from the Arabian/Persian Gulf were measured over 2 nesting seasons. Climate data from same period were regressed with nest temperatures to estimate incubation temperatures and hatchling sex ratios for the site from 1993 to 2100. Future hatchling sex ratios were estimated for 2 climate forecasts, one mid-range (SSP245) and one extreme (SSP585). Historical climate data showed female-biased sex ratios of 73.2 ± 12.1% from 1993 to 2017. Female biases from 2018 to 2100 averaged 85.7% ± 6.7% under the mid-range scenario and 87.9% ± 5.4% under the high-range scenario. In addition, predicted female hatchling production was >90% from 2054 and 2052 for SSP245 and SSP585, respectively. These results show that hawksbill primary sex ratios in Qatar are at risk of significant feminization by the year 2100 and that hawksbill turtle incubation temperatures in an extreme, understudied environment are already comparable to those predicted in tropical rookeries during the latter half of the 21stcentury. These results can help conservationists predict primary sex ratios for hawksbill turtles in the region in the face of 21st-century climate change.

Although many animals that perform sexual reproduction exhibit sexual dimorphism, individuals with intersex traits between the traits of males and females appear in some species, depending on environmental factors. Ptychognathus ishii, a varunid crab, exhibits distinctive sexual dimorphism in the morphology of its abdomen, chelipeds and setal tufts on the chelipeds. In this study, however, we report for the first time that intersex individuals with intermediate characters between those of males and females were occasionally found in wild populations. Morphological features of intersex individuals are described. Their taxonomic positions are identified based on DNA sequences of part of the mitochondrial cytochrome c oxidase I (COI) gene. It was shown that the intersexuality was induced by entoniscid parasites, because all intersex individuals were parasitized by entoniscid isopods, identified as Entionella sp. The apparent correlation between parasitism and morphological anomalies suggests that the parasitic isopods affect physiological conditions, leading to the feminization of male hosts.

Compared with the well-described XY sex determination system in mammals, the avian ZW sex determination system is poorly understood. Knockdown and overexpression studies identified doublesex and mab-3 related transcription factor 1 (DMRT1) as the testis-determining gene in chicken. However, the detailed effects of DMRT1 gene disruption from embryonic to adult development are not clear. Herein, we have generated DMRT1-disrupted chickens using the clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9) system, followed by an analysis of physiological, hormonal, and molecular changes in the genome-modified chickens. In the early stages of male chicken development, disruption of DMRT1 induced gonad feminization with extensive physiological and molecular changes; however, functional feminine reproductivity could not be implemented with disturbed hormone synthesis. Subsequent RNA-sequencing analysis of the DMRT1-disrupted chicken gonads revealed gene networks, including several novel genes linearly and non-linearly associated with DMRT1, which are involved in gonad feminization. By comparing the gonads of wild-type with the genome-modified chickens, a set of genes were identified that is involved in the ZW sex determination system independent of DMRT1. Our results extend beyond the Z-dosage hypothesis to provide further information about the avian ZW sex determination system and epigenetic effects of gonad feminization.

Transfeminine patients can experience significant gender dysphoria in vocal communication. Feminization laryngoplasty (FL) is a gender-affirming surgery developed to elevate speaking vocal range, as well as alter vocal resonance and laryngeal cosmesis. The purpose here was to appraise FL's long-term voice outcomes across a 17-year review period.Level III, retrospective study and description of technique.A single-institution transfeminine voice clinic.Voice data (speaking fundamental frequency [F0], lowest F0, highest F0, F0 range in both Hertz and semitones, and maximum phonation time [MPT]) were collected and assessed. Self-assessment of voice femininity and complications were documented.The 162 patients, all transfeminine women, had a mean age of 40 years with 36-month mean follow-up. There were significant increases in mean speaking F0 (Δ = 50 ± 30 Hz, Δ = 6 ± 3 semitones; P.001) and mean change in lowest F0 (Δ = 58 ± 31 Hz, Δ = 8 ± 4 semitones; P.001). There was no significant difference in mean change in highest F0 or MPT. There was significant improvement (Δ = 60% ± 39%; P.001) in perceptual self-assessment of vocal femininity. There was a 1.2% rate of major postoperative complications requiring inpatient admission or operative intervention. There were no differences in vocal outcomes between those patients who had less than 1-year follow-up and those who had 5-year follow-up.FL in this cohort was a safe and effective technique for increasing mean speaking F0, mean lowest F0, and voice gender perception over a prolonged follow-up period. These findings add to the possible treatments aimed at addressing the morbid dysphoria related to voice and communication for our transfeminine patients.

DNA methylation is an epigenetic mark that is influenced by underlying genetic profile, environment, and aging. It also plays a key role in female-specific X-chromosome silencing in mammals. In addition to X-linked DNA methylation, sex-specific methylation patterns are widespread across autosomal chromosomes and can be present from birth or arise over time. In individuals where gender identity and sex assigned at birth are markedly and consistently incongruent, as in the case of transgender people, feminization or masculinization may be sought through gender affirming hormone therapy (GAHT). In this study we profiled genome-wide DNA methylation in blood of transgender women and transgender men, before and during GAHT (6 months and 12 months into hormone treatment). We identified several thousand differentially methylated CpG sites (DMPs) in both people undergoing feminizing and masculinizing hormone therapy, the vast majority of which were progressive changes over time. Sex-specific DNA methylation patterns established in early development are largely refractory to change in association with GAHT. The small number of sex-DMPs that were affected by GAHT were those that become sex-specific during the lifetime, known as sex-and-age DMPs.

SummaryIn UV sexual systems, sex is determined during the haploid phase of the life cycle and males have a V chromosome whereas females have a U chromosome. Previous work in the brown algal model Ectocarpus revealed that the V chromosome has a dominant role in male sex determination and suggested that the female developmental program may occur by ‘default’, triggered in the absence of the male master sex determination gene(s). Here, we describe the identification of a genetically male giant kelp strain presenting phenotypic features typical of a female, despite lacking the U-specific region. The conversion to the female developmental program is however incomplete, because gametes of this feminised male are unable to produce the sperm-attracting pheromone lamoxirene. We identify the transcriptomic patterns underlying the male and female specific developmental programs, and reveal the faster evolutionary rates of male-biased genes compared to female-biased and unbiased genes. Moreover, we show that the phenotypic feminisation of the variant strain is associated with both feminisation and de-masculinisation of gene expression patterns. Importantly, the feminisation phenotype was associated with the dramatic downregulation of two V-specific genes including a candidate sex-determining gene on the V-specific region. Our results reveal the transcriptional changes associated with sexual differentiation in a UV system with marked sexual dimorphism, and contribute to disentangling the role of sex-linked genes and autosomal gene expression in the initiation of the male and female developmental programs. Overall, the data presented here imply that the U-specific region in the giant kelp is not required to initiate the female developmental program, but is critical to produce fully functional eggs, arguing against the idea that female is the ‘default’ sex in this species.

Endocrine variations, including possibly reduced exposure to androgens, may contribute to the development of male homosexuality, with animal models demonstrating same-sex mate preference with altered exposure during prenatal or early postnatal development. As similar studies in humans are impossible, indirect physical and cognitive measures of androgen exposure are used. Some studies suggest that physical measures affected by prenatal androgens, including the index-to-ring finger ratio, growth indices, and facial structure, are more "feminine" in gay men. Gay men also exhibit significant childhood gender non-conformity and a "feminized" anatomical and functional brain pattern in sexual arousal, as well as domains such as language, visuospatial skills and hemispheric relationships. However, many of these results are equivocal and may be confounded by other factors. Research has also been hampered by inconsistencies in the reporting of sexual orientation and the potentially unrepresentative populations of gay men studied, while additional complexities pertaining to gender conformity and sexual role may also influence results.

The presented clinical case of a girl with a salt-wasting form of congenital adrenal hyperplasia in combination with chronic recurrent infection and lower urinary tract dysfunction demonstrates the need to change conventional two-staged approach to surgical feminization in favor of a one-stage intervention in order to prevent a progression of genitourinary complications. After controlling for the underlying condition, the one-stage feminization was performed, including modified tightening introitoplasty using a Passerini-Glazel flap and a correction of hypertrophic clitoris and labia minora. Good short- and long-term results were achieved.

Mefentrifluconazole (trade name: Revysol®) is an agrochemical active ingredient from the new sub-class of isopropanol-triazole fungicides, with high selective fungicide activity. A full program of toxicity testing conducted according to OECD guidelines has shown mefentrifluconazole (MFZ) to be non-genotoxic and non-carcinogenic. Repeated dose studies in rats, mice and dogs identified the liver as the main target organ. Prenatal developmental toxicity studies in rats and rabbits did not indicate treatment-related embryofetal toxicity or teratogenicity up to the highest dose levels tested. In a two-generation dietary study in rats, the high dose level resulted in reduced food consumption and body weight gain throughout the dosing-period. Mating performance and fertility, estrous cycles, gestation length and pre-and post-natal survival of offspring were essentially unaffected and there was no evidence of masculinization of female pups or feminization of male pups. The screening strategy that led to the selection of MFZ was aimed to identify candidates with both high fungicidal activity and minimal likelihood of adverse side effects thought to arise from aromatase inhibition. The success of the selection strategy has been illustrated for MFZ by the absence in toxicity studies of effects that would indicate an endocrine disrupting potential.

Estrone, 17β-estradiol, 17α-ethynylestradiol, alkylphenols and alkylphenol ethoxylates, are endocrine disruptor compounds. In Portugal, the report of male fish feminization in Minho, Ave and Mondeg...

Arthropods harbour a variety of selfish genetic elements that manipulate reproduction to be preferentially transmitted to future generations. A major ongoing question is to understand how these elements persist in nature. In this study, we examine the population dynamics of an unusual selfish sex ratio distorter in a recently discovered species of booklouse, Liposcelis sp. (Psocodea: Liposcelididae) to gain a better understanding of some of the factors that may affect the persistence of this element. Females that carry the selfish genetic element only ever produce daughters, although they are obligately sexual. These females also only transmit the maternal half of their genome. We performed a replicated population cage experiment, varying the initial frequency of females that harbour the selfish element, and following female frequencies for 20 months. The selfish genetic element persisted in all cages, often reaching very high (and thus severely female-biased) frequencies. Surprisingly, we also found that females that carry the selfish genetic element had much lower fitness than their nondistorter counterparts, with lower lifetime fecundity, slower development and a shorter egg-laying period. We suggest that differential fitness plays a role in the maintenance of the selfish genetic element in this species. We believe that the genetic system in this species, paternal genome elimination, which allows maternal control of offspring sex ratio, may also be important in the persistence of the selfish genetic element, highlighting the need to consider species with diverse ecologies and genetic systems when investigating the effects of sex ratio manipulators on host populations.

Sex differences in the anatomy and physiology of the vertebrate preoptic area (POA) arise during development, and influence sex-specific reproductive functions later in life. Relative to masculinization, mechanisms for feminization of the POA are not well understood. The purpose of this study was to induce sex change from male to female in the anemonefish Amphiprion ocellaris, and track the timing of changes in POA cytoarchitecture, composition of the gonads and circulating sex steroid levels. Reproductive males were paired together and then sampled after 3 weeks, 6 months, 1 year and 3 years. Results show that as males change sex into females, number of medium cells in the anterior POA (parvocellular region) approximately double to female levels over the course of several months to 1 year. Feminization of gonads, and plasma sex steroids occur independently, on a variable timescale, up to years after POA sex change has completed. Findings suggest the process of POA feminization is orchestrated by factors originating from within the brain as opposed to being cued from the gonads, consistent with the dominant hypothesis in mammals. Anemonefish provide an opportunity to explore active mechanisms responsible for female brain development in an individual with male gonads and circulating sex steroid levels.

Facial gender-affirming surgery can have significant impact on patient quality of life for some gender-dysphoric patients. Lower jaw contouring can be used to harmonize the face during facial gender-affirming surgery through masculinization or feminization. During feminization, the mandibular angle and body and chin are reduced in width and size. During masculinization, augmentation of the mandibular angle and body and chin are completed with alloplastic implants, fat, or bone. Complications are minimal. Further research is needed on outcomes of these procedures.

The expression profiles of key genes associated with sex differentiation in vertebrates, namely, amh, ar, cyp19, dmrt1, erα, erβ, foxl2, sox9, star, and vtg, were analyzed in the gonads, liver, muscle, and brain of Russian sturgeon (Acipenser gueldenstaedtii). The aims of this study were to determine in which tissue the signal for sex differentiation primarily occurs, and which factors are most important for gonadal differentiation. The sturgeons included in the study (180 days post-hatching; n = 20) were at the beginning of gonadal differentiation; five females, seven males, and eight individuals with disturbed germinal tissue development were identified. All of the examined genes except for star had diverse sex-related expression profiles in the brain. By contrast, in the gonads, only foxl2 expression was sex-dependent. With the exception of star and cyp19, all of the other genes were expressed in the muscle and liver, but there were no significant differences between sexes. The expression profiles of the analyzed genes in the brain were atypical, indicating feminization. This finding was in agreement with the high occurrence of individuals sharing female and male germinal tissue characteristics. The data presented here suggest that the sturgeon brain is the primary organ that stimulates other organs and tissues to differentiate into male or female, and that dmrt1 and foxl2 play major roles in sex differentiation in this species.

This article provides an overview of the key concepts and techniques of facial feminization surgery. The author reviews 20 years of experience with thousands of patients.

The transcription factor Doublesex (Dsx) has a conserved function in controlling sexual morphological differences in insects, but our knowledge on its role in regulating sexual behavior is widely limited to Drosophila. Here, we show in the parasitoid wasp Nasonia vitripennis that males whose Dsx gene had been silenced by RNA interference (NvDsx-i) underwent a three-level pheromonal feminization: (1) NvDsx-i males were no longer able to attract females from a distance, owing to drastically reduced titers of the abdominal long-range sex pheromone. (2) NvDsx-i males were courted by wild-type males like females which correlated with a lower abundance of alkenes in their cuticular hydrocarbon (CHC) profiles. Supplementation of NvDsx-i male CHC profiles with realistic amounts of synthetic (Z)-9-hentriacontene (Z9C31), the most significantly reduced alkene in NvDsx-i males, interrupted courtship by wild-type conspecific males. Supplementation of female CHC profiles with Z9C31 reduced courtship and mating attempts by wild-type males. These results prove that Z9C31 is crucial for sex discrimination in Nasonia. (3) Nvdsx-i males were hampered in eliciting female receptivity during courtship and thus experienced severely reduced mating success, suggesting that they are unable to produce the hitherto unidentified oral aphrodisiac pheromone reported in N. vitripennis males. We conclude that Dsx is a multi-level key regulator of pheromone-mediated sexual communication in N. vitripennis. Silencing Dsx by RNA interference provides a new avenue for unraveling the molecular mechanisms underlying the pheromone-mediated sexual communication in insects.

To examine the effect and mechanism of thyroid hormone on gonadal sex differentiation, Takifugu rubripes larvae were treated with goitrogen (methimazole, MET, 1000 μg/g), and thyroxine (T4, 2nM) from 25 to 80 days after hatching (dah). Gonadal histology and sex ratios of fish were then determined at 80 dah. MET treatment induced masculinization, but T4 treatment did not induce feminization in T. rubripes larvae. Transcriptomic analysis of gonads at 80 dah was then conducted. Among the large number of differentially expressed genes between the groups, the expression of foxl2, cyp19a1a, and dmrt1 was altered. The expression of foxl2, cyp19a1a, dmrt1 and gsdf at 25, 40, 55 days after treatment (dat) was further analyzed by qPCR. MET treatment suppressed the expression of foxl2 and cyp19a1a, and induced the expression of dmrt1 in genetic females (p < 0.05). Additionally, T4 treatment induced an increase in the expression of cyp19a1a in genetic XY gonads only at 25 dat. However, the increase in cyp19a1a expression did not continue to 40 and 55 dat. This may explain why feminization of larvae was not found in the T4-treated group. Thus, the present study provides the first evidence that MET treatment causes masculinization in teleost fish. The effects of MET-induced masculinization in T. rubripes may act primarily via suppression of the expression of foxl2 and cyp19a1a, and stimulation of the expression of dmrt1. Moreover, the effects of higher concentrations of T4 or different concentrations of T3, on sex differentiation require further testing.

International audience; Sex determination is a complex process that can be influenced by environment in various taxa. Disturbed environments can affect population sex ratios and thus threaten their viability. Emerging evidences support a role of epigenetic mechanisms, notably DNA methylation, in environmental sex determination (ESD). In this work, using zebrafish as model and a transgenerational experiment comprising 4 successive generations, we report a strength link between the promotor methylation level of three genes in female gonads and population sex ratio. One generation of zebrafish was exposed throughout its lifetime to cadmium (Cd), a non-essential metal, at an environmentally relevant concentration. The subsequent generations were not exposed. At the first and the third generation a subset of individuals was exposed to an elevated temperature, a well-known masculinizing factor in zebrafish. While heat was associated to an increase in the methylation level of cyp19a1a gene and population masculinization, foxl2a/dmrt1 methylation levels appeared to be influenced by Cd and fish density leading to offspring feminization. Ancestral Cd exposure indeed led to a progressive feminization of the population over generations and affected the sex plastic response of zebrafish in response to heat. The effect of Cd on the methylation level of foxl2a was observed until the third generation, supporting potential transgenerational inheritance. Our results support (i) a key role of cyp19a1a methylation in SD in zebrafish in response to environmental cues and (ii) the fact that the environment experienced by parents, namely mothers in the present case, can affect their offspring sex ratio via environment-induced DNA methylation changes in gonads.

Clascoterone is an androgen receptor inhibitor which has been approved by the United States Food and Drug Administration for the topical treatment of acne vulgaris in patients 12 years of age and older. It competes with androgens, especially dihydrotestosterone, for androgen-receptor binding and limits their binding, thus inhibiting downstream signaling of pathways involved in the pathogenesis of acne. It inhibits androgen receptor-regulated gene transcription, and antagonizes lipid and inflammatory cytokine production in a dose-dependent manner in human primary sebocytes. Clascoterone is commercially available as 1% (10 mg/g) cream. Adverse effects of topical clascoterone are mild and infrequent, and are mostly limited to local skin reactions. Long-term safety studies have shown an absence of systemic antiandrogenic effects like reduced libido or feminization in male participants. Clascoterone seems a promising topical drug with a novel mechanism of action that could be added to the armamentarium of therapies for acne.

Gender dysphoria describes the distress associated with having a gender identity that differs from one’s birth-assigned sex. To relieve this distress, transgender, and gender diverse (henceforth, trans) individuals commonly undergo medical transition involving hormonal treatments. Current hormonal treatment guidelines cater almost exclusively for those who wish to transition from male to female or vice versa. In contrast, there is a dearth of hormonal options for those trans individuals who identify as non-binary and seek an androgynous appearance that is neither overtly male nor female. Though prolonged puberty suppression with gonadotrophin releasing hormone agonists (GnRHa) could in theory be gender-affirming by preventing the development of unwanted secondary sex characteristics, this treatment option would be limited to pre- or peri-pubertal adolescents and likely have harmful effects. Here, we discuss the theoretical use of Selective Estrogen Receptor Modulators (SERMs) for non-binary people assigned male at birth (AMAB) who are seeking an androgynous appearance through partial feminization without breast growth. Given their unique range of pharmacodynamic effects, SERMs may represent a potential gender-affirming treatment for this population, but there is a lack of knowledge regarding their use and potentially adverse effects in this context.

Purpose: Subcutaneous injections, or “fillers,” are used illicitly and in large quantities by trans women for feminization. They are associated with severe complications, but data on their use are limited, especially in places with widespread access to safe gender-affirming care. Our analysis seeks to assess the prevalence, correlates, and complications of filler use to inform prevention and treatment. Methods: A secondary analysis of cross-sectional survey data from the Trans* National Study conducted from May 2016 to December 2017 of 631 adult trans women in the San Francisco Bay Area, California, recruited using respondent-driven sampling. Results: Around 65/631 participants (10.3%) reported filler use. Filler use was highest among Latinas (21.3% vs. 3.8% among whites, p

Reproductive parasitism is a specific form of symbiosis in which a microorganism alters the reproduction of the host by interfering with the mechanisms of sex development. The review considers four changes in reproduction — male killing, parthenogenesis, feminization, and cytoplasmic incompatibility — determined by cytoplasmic bacteria. The cytogenetic and molecular genetic mechanisms of interaction between partners in the symbiotic system are discussed, including the comparative analysis of molecular-genetic factors responsible for reproductive parasitism. The features of the interaction between an insect and bacteria in symbiosis with various systems for determining the sex of the host, male and female heterogamy and haplodiploidy, are considered. Studies of cytoplasmic incompatibility are of great practical importance, since they open up prospects for non-invasive engineering on natural insect populations for biocontrol.