Missing Piece Connecting Male and Female Sex Determination

Abstract Background and Aims The ability of individuals to change sex during their lifetime is known as environmental sex determination (ESD). This represents a unique life history trait, allowing plants to allocate resources differentially to male and female functions across lifetimes, potentially maximizing fitness in response to changing environmental or internal cues. In this study, Acer pensylvanicum, a species with an unconfirmed sex determination system, was investigated to see what patterns in sex expression existed across multiple years, if there were sex-based differences in growth and mortality, and whether this species conformed to theoretical predictions that females are larger and in better condition. Methods Patterns of sex expression were documented over 4 years in a phenotypically subdioecious A. pensylvanicum population located in New Jersey, USA, and data on size, mortality, health and growth were collected. A machine-learning algorithm known as a boosted classification tree was used to develop a model to predict the sex of a tree based on its condition, size and previous sex. Results In this study, 54 % of the trees switched sex expression during a 4-year period, with 26 % of those trees switching sex at least twice. Consistently monoecious trees could change relative sex expression by as much as 95 %. Both size and condition were influential in predicting sex, with condition exerting three times more relative influence than size on expressed sex. Contrary to theoretical predictions, the model showed that full female sex expression did not increase with size. Healthy trees were more likely to be male; predicted female sex expression increased with deteriorating health. Growth rate negatively correlated with multiple years of female sex expression. Populations maintained similar male-skewed sex ratios across years and locations and may result from differential mortality: 75 % of dead trees flowered female immediately before death. Conclusions This study shows conclusively that A. pensylvanicum exhibits ESD and that femaleness correlates with decreased health, in contrast to prevailing theory. The mortality findings advance our understanding of puzzling non-equilibrium sex ratios and life history trade-offs resulting from male and female sex expression.

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wnt4a promotes female development and reproductive duct elongation in zebrafish

10.1101/421362 ◽

2018 ◽

Author(s):

Michelle E. Kossack ◽

Samantha K. High ◽

Rachel E. Hopton ◽

Yi-lin Yan ◽

John H. Postlethwait ◽

...

Keyword(s):

Sex Determination ◽

Sex Chromosome ◽

Ovary Development ◽

Last Common Ancestor ◽

Loss Of Function ◽

Female Development ◽

Male And Female ◽

Female Sex ◽

Somatic Gonad ◽

Duct Development

ABSTRACTIn laboratory strains of zebrafish, sex determination occurs in the absence of a typical sex chromosome and it is not known what regulates the proportion of animals that develop as male or female. Many sex determination and differentiation genes that act downstream of a sex chromosome are well conserved among vertebrates, but studies that test their contribution to this process have mostly been limited to mammalian models. In mammals, WNT4 is a signaling ligand that is essential for ovary and Müllerian duct development, where it function, in part, to antagonize the male-promoting FGF9 signal. Wnt4 is highly conserved in non-mammalian vertebrates, but it is not known if Wnt4 plays a role in sex determination and/or the differentiation of sex organs outside of mammals. This is an especially interesting question in teleost, such as zebrafish, because they lack an Fgf9 ortholog. Here we show that wnt4a is the ortholog of mammalian Wnt4, and that wnt4b was present in the last common ancestor of humans and zebrafish, but was lost in mammals. We found that wnt4a is expressed in the somatic cells of juvenile gonads during the time sex determination likely occurs. We show that wnt4a loss-of-function mutants develop predominantly as males and conclude that wnt4a activity promotes female sex determination in zebrafish. Additionally, both male and female wnt4a mutants are sterile because their reproductive ducts do not connect to the vent, where wnt4a is normally expressed. Yet when dissected from homozygous wnt4a mutant gonads, both sperm and eggs can produce fertile offspring. Together these results strongly argue that Wnt4a is a conserved regulator of female sex determination and reproductive duct development in non-mammalian vertebrates.SUMMARYWnt4 is a key regulator of ovary development in mammals, but it is not known if it plays a similar role in other vertebrates. Here we show that zebrafish wnt4a is the ortholog of mammalian Wnt4. We show that wnt4a is expressed in zebrafish somatic gonad cells during the time sex determination likely occurs. Through analysis of wnt4a mutants, we show that Wnt4a promotes female sex determination and the development of the male and female reproductive. We conclude that Wnt4/Wnt4a is likely a conserved regulator of ovarian and reproductive duct development in all vertebrates

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Male and female sex determination by fluorescence assay of Barr bodies and Y bodies in interphase cells

European Journal of Obstetrics & Gynecology ◽

10.1016/0028-2243(72)90056-1 ◽

1972 ◽

Vol 2 (1) ◽

pp. 19-27

Author(s):

M.Th. Matton

Keyword(s):

Sex Determination ◽

Fluorescence Assay ◽

Male And Female ◽

Female Sex ◽

Interphase Cells

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Gonadal Development and Tumor Formation at the Crossroads of Male and Female Sex Determination

Sexual Development ◽

10.1159/000329477 ◽

2011 ◽

Vol 5 (4) ◽

pp. 167-180 ◽

Cited By ~ 46

Author(s):

M. Cools ◽

K.P. Wolffenbuttel ◽

S.L.S. Drop ◽

J.W. Oosterhuis ◽

L.H.J. Looijenga

Keyword(s):

Sex Determination ◽

Gonadal Development ◽

Tumor Formation ◽

Male And Female ◽

Female Sex

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Role of sex hormones in lung cancer

Experimental Biology and Medicine ◽

10.1177/15353702211019697 ◽

2021 ◽

pp. 153537022110196

Author(s):

Nathalie Fuentes ◽

Miguel Silva Rodriguez ◽

Patricia Silveyra

Keyword(s):

Lung Cancer ◽

Sex Differences ◽

Sex Hormones ◽

Hormone Receptors ◽

Occupational Exposures ◽

Lung Carcinogenesis ◽

Male And Female ◽

Female Sex ◽

Incidence And Mortality ◽

Cancer Rates

Lung cancer represents the world’s leading cause of cancer deaths. Sex differences in the incidence and mortality rates for various types of lung cancers have been identified, but the biological and endocrine mechanisms implicated in these disparities have not yet been determined. While some cancers such as lung adenocarcinoma are more commonly found among women than men, others like squamous cell carcinoma display the opposite pattern or show no sex differences. Associations of tobacco product use rates, susceptibility to carcinogens, occupational exposures, and indoor and outdoor air pollution have also been linked to differential rates of lung cancer occurrence and mortality between sexes. While roles for sex hormones in other types of cancers affecting women or men have been identified and described, little is known about the influence of sex hormones in lung cancer. One potential mechanism identified to date is the synergism between estrogen and some tobacco compounds, and oncogene mutations, in inducing the expression of metabolic enzymes, leading to enhanced formation of reactive oxygen species and DNA adducts, and subsequent lung carcinogenesis. In this review, we present the literature available regarding sex differences in cancer rates, associations of male and female sex hormones with lung cancer, the influence of exogenous hormone therapy in women, and potential mechanisms mediated by male and female sex hormone receptors in lung carcinogenesis. The influence of biological sex on lung disease has recently been established, thus new research incorporating this variable will shed light on the mechanisms behind the observed disparities in lung cancer rates, and potentially lead to the development of new therapeutics to treat this devastating disease.

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The Sex Determination Cascade in the Silkworm

Genes ◽

10.3390/genes12020315 ◽

2021 ◽

Vol 12 (2) ◽

pp. 315

Author(s):

Xu Yang ◽

Kai Chen ◽

Yaohui Wang ◽

Dehong Yang ◽

Yongping Huang

Keyword(s):

Sex Determination ◽

Molecular Mechanisms ◽

Future Research ◽

Model Species ◽

Male And Female ◽

Master Regulators ◽

Primary Signal ◽

Basic Understanding ◽

Female Specific ◽

Working Mechanisms

In insects, sex determination pathways involve three levels of master regulators: primary signals, which determine the sex; executors, which control sex-specific differentiation of tissues and organs; and transducers, which link the primary signals to the executors. The primary signals differ widely among insect species. In Diptera alone, several unrelated primary sex determiners have been identified. However, the doublesex (dsx) gene is highly conserved as the executor component across multiple insect orders. The transducer level shows an intermediate level of conservation. In many, but not all examined insects, a key transducer role is performed by transformer (tra), which controls sex-specific splicing of dsx. In Lepidoptera, studies of sex determination have focused on the lepidopteran model species Bombyx mori (the silkworm). In B. mori, the primary signal of sex determination cascade starts from Fem, a female-specific PIWI-interacting RNA, and its targeting gene Masc, which is apparently specific to and conserved among Lepidoptera. Tra has not been found in Lepidoptera. Instead, the B. mori PSI protein binds directly to dsx pre-mRNA and regulates its alternative splicing to produce male- and female-specific transcripts. Despite this basic understanding of the molecular mechanisms underlying sex determination, the links among the primary signals, transducers and executors remain largely unknown in Lepidoptera. In this review, we focus on the latest findings regarding the functions and working mechanisms of genes involved in feminization and masculinization in Lepidoptera and discuss directions for future research of sex determination in the silkworm.

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Meiotic gynogenesis revealed not homogametic female sex determination system in Siberian sturgeon (Acipenser baeri Brandt)

Aquaculture ◽

10.1016/j.aquaculture.2010.04.011 ◽

2010 ◽

Vol 305 (1-4) ◽

pp. 174-177 ◽

Cited By ~ 33

Author(s):

Dorota Fopp-Bayat

Keyword(s):

Sex Determination ◽

Siberian Sturgeon ◽

Acipenser Baeri ◽

Female Sex ◽

Determination System ◽

Sex Determination System ◽

Meiotic Gynogenesis

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Gene networks underlying functional sex in Sparidae (Pisces, Teleostei)

10.12681/eadd/44179 ◽

2018 ◽

Author(s):

Αλέξανδρος Τσακογιάννης

Keyword(s):

Gene Expression ◽

Sex Determination ◽

Gene Networks ◽

Expression Patterns ◽

Gene Families ◽

Male And Female ◽

Dentex Dentex ◽

The Common ◽

Model Fish Species ◽

Model Fish

The differences between sexes and the concept of sex determination have always fascinated, yet troubled philosophers and scientists. Among the animals that reproduce sexually, teleost fishes show a very wide repertoire of reproductive modes. Except for the gonochoristic species, fish are the only vertebrates in which hermaphroditism appears naturally. Hermaphroditism refers to the capability of an organism to reproduce both as male and female in its life cycle and there are various forms of it. In sequential hermaphroditism, an individual begins as female first and then can change sex to become male (protogyny), or vice versa (protandry). The diverse sex-phenotypes of fish are regulated by a variety of sex determination mechanisms, along a continuum of environmental and heritable factors. The vast majority of sexually dimorphic traits result from the differential expression of genes that are present in both sexes. To date, studies regarding the sex-specific differences in gene expression have been conducted mainly in sex determination systems of model fish species that are well characterized at the genomic level, with distinguishable heteromorphic sex chromosomes, exhibiting genetic sex determination and gonochorism. Among teleosts, the Sparidae family is considered to be one of the most diversified families regarding its reproductive systems, and thus is a unique model for comparative studies to understand the molecular mechanisms underlying different sexual motifs. In this study, using RNA sequencing, we studied the transcriptome from gonads and brains of both sexes in five sparid species, representatives of four different reproductive styles. Specifically, we explored the sex-specific expression patterns of a gonochoristic species: the common dentex Dentex dentex, two protogynous hermaphrodites: the red porgy Pagrus pagrus and the common pandora Pagellus erythrinus, the rudimentary hermaphrodite sharpsnout seabream Diplodus puntazzo, and the protandrous gilthead seabream Sparus aurata. We found minor sex-related expression differences indicating a more homogeneous and sexually plastic brain, whereas there was a plethora of sex biased gene expression in the gonads. The functional divergence of the two gonadal types is reflected in their transcriptomic profiles, in terms of the number of genes differentially expressed, as well as the expression magnitude (i.e. fold-change differences). The observation of almost double the number of up-regulated genes in males compared to females indicates a male-biased expression tendency. Focusing on the pathways and genes implicated in sex determination/differentiation, we aimed to unveil the molecular pathways through which these non-model fish species develop a masculine or a feminine character. We observed the implicated pathways and major gene families (e.g. Wnt/b-catenin pathway and Retinoic-acid signaling pathway, Notch, TGFβ) behind sex-biased expression and the recruitment of known sex-related genes either to male or female type of gonads in these fish. (e.g Dmrt1, Sox9, Sox3, Cyp19a, Filgla, Ctnnb1, Gsdf9, Stra6 etc.). We also carefully investigated the presence of genes reported to be involved in sex determination/differentiation mechanisms in other vertebrates and fish and compared their expression patterns in the species under study. The expression profiling exposed known candidate molecular-players/genes establishing the common female (Cyp19a1, Sox3, Figla, Gdf9, Cyp26a, Ctnnb1, Dnmt1, Stra6) and male identity (Dmrt1, Sox9, Dnmt3aa, Rarb, Raraa, Hdac8, Tdrd7) of the gonad in these sparids. Additionally, we focused on those contributing to a species-specific manner either to female (Wnt4a, Dmrt2a, Foxl2 etc.) or to male (Amh, Dmrt3a, Cyp11b etc.) characters, and discussed the expression patterns of factors that belong to important pathways and/or gene families in the SD context, in our species gonadal transcriptomes. Taken together, most of the studied genes form part of the cascade of sex determination, differentiation, and reproduction across teleosts. In this study, we focused on genes that are active when sex is established (sex-maintainers), revealing the basic “gene-toolkit” & gene-networks underlying functional sex in these five sparids. Comparing related species with alternative reproductive styles, we saw different combinations of genes with conserved sex-linked roles and some “handy” molecular players, in a “partially- conserved” or “modulated” network formulating the male and female phenotype. The knowledge obtained in this study and tools developed during the process have set the groundwork for future experiments that can improve the sex control of this species and help the in-deep understanding the complex process of sex differentiation in the more flexible multi-component systems as these studied here.

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