Gender Disparities in Bladder Cancer

Biological sex is an independent risk factor of cancer. Men are three to five times more likely than women to develop bladder cancer even when known risk factors are taken into consideration. Development of sex in mammals is often viewed as a two-step process. The first step is sex determination, of which the XX and XY sex chromosome complements trigger gonad differentiation to form the ovary and testis, respectively. After that, sex hormones secreted by gonads initiate sexually dimorphic differentiation of nongonadal tissues. However, this model has been challenged by recent findings revealing an independent contribution of sex chromosomes to sexual dimorphism. In this chapter, we discuss how the sex chromosomes and sex hormones together cause gender disparities in bladder cancer. We propose a concept of epigenetic sex – epigenetic differences between males and females – and suggest that the sex epigenome is a previously unknown biasing factor contributing to gender disparities in bladder cancer.

Oestrogen Activates the MAP3K1 Cascade and β-Catenin to Promote Granulosa-Like Cell Fate in a Human Testis-Derived Cell Line

Sex determination triggers the differentiation of the bi-potential gonad into either an ovary or testis. In non-mammalian vertebrates, the presence or absence of oestrogen dictates gonad differentiation, while in mammals, this mechanism has been supplanted by the testis-determining gene SRY. Exogenous oestrogen can override this genetic trigger to shift somatic cell fate in the gonad towards ovarian developmental pathways by limiting the bioavailability of the key testis factor SOX9 within somatic cells. Our previous work has implicated the MAPK pathway in mediating the rapid cellular response to oestrogen. We performed proteomic and phosphoproteomic analyses to investigate the precise mechanism through which oestrogen impacts these pathways to activate β-catenin—a factor essential for ovarian development. We show that oestrogen can activate β-catenin within 30 min, concomitant with the cytoplasmic retention of SOX9. This occurs through changes to the MAP3K1 cascade, suggesting this pathway is a mechanism through which oestrogen influences gonad somatic cell fate. We demonstrate that oestrogen can promote the shift from SOX9 pro-testis activity to β-catenin pro-ovary activity through activation of MAP3K1. Our findings define a previously unknown mechanism through which oestrogen can promote a switch in gonad somatic cell fate and provided novel insights into the impacts of exogenous oestrogen exposure on the testis.

Labile sex chromosomes and a novel candidate sex-determination gene in the Australian freshwater fish family Percichthyidae

Sex-specific ecology has management implications, but rapid sex-chromosome turnover in fishes hinders development of markers to sex monomorphic species. Here, we use annotated genomes and reduced-representation sequencing data for two Australian percichthyids, the Macquarie perch Macquaria australasica and the golden perch M. ambigua, and whole genome resequencing data for 50 Macquarie perch of each sex, to detect sex-linked loci, identify a candidate sex-determining gene and develop an affordable sexing assay. In-silico pool-seq tests of 1,492,004 Macquarie perch SNP loci revealed that a 275-Kb scaffold, containing the transcription factor SOX1b gene, was enriched for gametologous loci. Within this scaffold, 22 loci were sex-linked in a predominantly XY system, with females being homozygous at all 22, and males being heterozygous at two or more. Seven XY-gametologous loci were within a 146-bp region. Being ~38 Kb upstream of SOX1b, it might act as an enhancer controlling SOX1b transcription in the bipotential gonad that drives gonad differentiation. A PCR-RFLP sexing assay, targeting one of the Y-linked SNPs, tested in 66 known-sex Macquarie perch and two individuals of each sex of three confamilial species, and amplicon sequencing of 400 bp encompassing the 146-bp region, revealed that the few sex-linked positions differ between species and between Macquarie perch populations. This indicates sex-chromosome lability in Percichthyidae, also supported by non-homologous scaffolds containing sex-linked loci for Macquarie- and golden perches. The resources developed here will facilitate genomic research in Percichthyidae. Sex-linked markers will be useful for determining genetic sex in some populations and studying sex chromosome turnover.

MicroRNAs in amniotic fluid and maternal blood plasma associated with sex determination and early gonad differentiation in cattle

MicroRNAs (miRNAs), as gene expression regulators, may play a critical role during the sex determination process. We hypothesised that the expression of miRNAs in amniotic fluid (AF) and maternal blood plasma (MP) during this process would be affected by the sex of the embryo. Amniotic fluid and MP were collected from six pregnant heifers (3 carrying a single male and 3 a single female embryo) following slaughter on Day 39 post insemination, coinciding with the peak of SRY expression. Samples (6 AF and 6 MP) were profiled using a miRNA Serum/Plasma Focus PCR Panel. Differentially expressed (DE) miRNAs were identified in AF (n = 5) and associated MP (n = 56) of male vs female embryos (P < 0.05). Functional analysis showed that inflammatory and immune response were amongst the 13 biological processes enriched by miRNAs DE in MP in the male group (FDR < 0.05), suggesting that these sex-dependent DE miRNAs may be implicated in modulating the receptivity of the dam to a male embryo. Further, we compared the downstream targets of the sex-dependent DE miRNAs detected in MP with genes previously identified as DE in male vs female genital ridges. The analyses revealed potential targets that might be important during this developmental stage such as SHROOM2, DDX3Y, SOX9, SRY, PPP1CB, JARID2, USP9X, KDM6A, and EIF2S3. Results from this study highlight novel aspects of sex determination and embryo-maternal communication in cattle such as the potential role of miRNAs in gonad development as well as in the modulation of the receptivity of the dam to a male embryo.

A preliminary study on the size structure and sex ratio of orange-spotted grouper (Epinephelus coioides Hamilton, 1822) harvested from Kwandang Bay, Sulawesi Sea, Indonesia

Orange-spotted grouper is one of the coral reef fish has the economic value and exploited by local fisherman. Information about the size structure and sex ratio are urgent to formulate a policy for sustainability. This research aims to analyze the size structure and sex ratio of the orange-spotted grouper in Kwandang Bay. The research was conducted from December 2016 to November 2017. Sampling is carried out twice a month for one year. The total sample of orange-spotted grouper used for the analysis of the sex ratio was 149 individuals. Sample of orange-spotted grouper collected from fish landed and middlemen (grouper traders) at the Kwandang Fishing Port. Data analysis applying chi-square. The results show that males bigger than females. The sex ratio of orange-spotted grouper is 87.25 % female, 7.38 % male, and 5.37 % hermaphrodites. Orange-spotted grouper dominated by females and undergoes a gonad differentiation to male (protogynous hermaphrodite). It is concluded that The size of the male orange-spotted grouper is larger than that of the female grouper. The caught orange-spotted grouper is dominated by the female phase and undergoes a differentiation of the gonad from female to male (protogynous hermaphrodite)

Diverse Regulation but Conserved Function: SOX9 in Vertebrate Sex Determination

Sex determination occurs early during embryogenesis among vertebrates. It involves the differentiation of the bipotential gonad to ovaries or testes by a fascinating diversity of molecular switches. In most mammals, the switch is SRY (sex determining region Y); in other vertebrates it could be one of a variety of genes including Dmrt1 or dmy. Downstream of the switch gene, SOX9 upregulation is a central event in testes development, controlled by gonad-specific enhancers across the 2 Mb SOX9 locus. SOX9 is a ‘hub’ gene of gonadal development, regulated positively in males and negatively in females. Despite this diversity, SOX9 protein sequence and function among vertebrates remains highly conserved. This article explores the cellular, morphological, and genetic mechanisms initiated by SOX9 for male gonad differentiation.

Gonadal Differentiation of Nilem Fish (Osteochilus vittatus) Utilizing Temperature Treatment

Background: Gonad differentiation in some teleostei is a critical phase of gonad development. Gonad differentiation in some fish such as the tilapia group is influenced by environmental factors, namely temperature. The aim of this study was to determine the differentiation process of Nilem fish gonads (Osteochilus vittatus) under the influence of temperature. Methods: One day after fertilization (days postfertilization/dpf) fish were exposed to different medium temperature ranges, namely: 28-29 oC, 30-31 oC, 32-33 oC, and room temperature as a control for 35 days. The percentage of fish survival was calculated on the 35th day by calculating the number of surviving fish divided by the total number of fish in 1 tank times 100%. Thirty fish in each treatment were measured for body length at day 10 dpf and day 35 dpf to determine fish growth. Six fish 35 dpf from each treatment were fixed in 70% alcohol for making histological preparations using the paraffin method, Haematoxylin-Eosin staining. Fish survival data growth data in the form of fish length were analyzed using Anova. Gonadal differentiation data were analyzed descriptively. Results: There was no significant difference in the growth of fish in all treatment and control groups. The average survival rate of fish in all treatment and control groups was 100%. Observation of the gonads showed that the gonads were not differentiated in all treatment and control groups. Conclusion: The room temperature range up to 33 oC supports the growth of Nilem fish with gonad development in the indifferent gonad stage.

Masculinization of Tropical Eel Anguilla bicolor McClelland in Different Population Density

In general, female eel dominates the results of catching eel in the river. Male fish dare rarely found in nature, therefore masculinization is necessary for obtaining in males. The administration of 17α-methyltestosterone to masculinize Anguilla bicolor McClelland. It is a synthetic anabolic-androgenic steroid which has potential to endocrine disrupter that disturbed function of normal reproduction in human or animal. It urgently needed that a masculinization technique needs to study the use of an environmental factor. Population density is one of the environmental factors that influence gender determination (ESD-environmental dependent sex determination). This will result in increased cortisol secretion, which will further stimulate the synthesis of 11-KT steroids that affect male gonad differentiation. This study aims to induce masculinization in tropical eel Anguilla bicolor McClelland in different density. Three treatments and three replicates conducted the research. The treatments were one fish.48 L-1, two fish.48 L-1 and three fish.48 L-1. Eels size was approximately similar, at 16,78 g±0,62 in weight, and 25,38 cm±0,15 in length were either culture in brackish water for eight weeks. The results showed that density population treatment significantly increased the Fin Index (P<0.05), but no sign for Eye Index, GSI, HSI, and testosterone level. The highest male population (77,8%) achieves at the highest density treatment, three fish.48 L-1 population density. It can be concluded, based on reproductive observations, population density does not affect gonad maturity/puberty, but the high population density (3 fish.48 L-1)stimulates Anguilla bicolor McClelland masculinization.