Molecular players involved in temperature-dependent sex determination and sex differentiation in Teleost fish

The molecular mechanisms that underlie sex determination and differentiation are conserved and diversified. In fish species, temperature-dependent sex determination and differentiation seem to be ubiquitous and molecular players involved in these mechanisms may be conserved. Although how the ambient temperature transduces signals to the undifferentiated gonads remains to be elucidated, the genes downstream in the sex differentiation pathway are shared between sex-determining mechanisms. In this paper, we review recent advances on the molecular players that participate in the sex determination and differentiation in fish species, by putting emphasis on temperature-dependent sex determination and differentiation, which include temperature-dependent sex determination and genetic sex determination plus temperature effects. Application of temperature-dependent sex differentiation in farmed fish and the consequences of temperature-induced sex reversal are discussed.     

Studies of gonadal sex differentiation

Gonadal differentiation has a determinative influence on sex development in human embryos. Disorders of sexual development (DSD) have been associated with persistent embryonal differentiation stages. Between 1998 and 2015, 139 female patients with various (DSD) underwent operations at the Scientific Center of Obstetrics, Gynaecology and Perynatology in Moscow, Russia. Clinical investigations included karyotyping, ultrasound imaging, hormonal measurement and investigations of gonadal morphology. The male characteristics in the embryo are imposed by testicular hormones. When these are absent or inactive, the fetus may be arrested at between developmental stages, or stay on indifferent stage and become phenotypically female. A systematic analysis of gonadal morphology in DSD patients and a literature review revealed some controversies and led us to formulate a new hypothesis about sex differentiation. Proliferation of the mesonephric system (tubules and corpuscles) in the gonads stimulates the masculinization of gonads to testis. Sustentacular Sertoli cells of the testes are derived from mesonephric excretory tubules, while interstitial Leydig cells are derived from the original mesenchyme of the mesonephros. According of the new hypothesis, the original mesonephric cells (tubules and corpuscles) potentially persist in the ovarian parenchyma. In female gonads, some mesonephric excretory tubules regress and lose the tubular structure, but form ovarian theca interna and externa, becoming analogous to the sustentacular Sertoli cells in the testis. The ovarian interstitial Leydig cells are derived from intertubal mesenchyme of the mesonephros, similar to what occurs in male gonads (testis). Surprisingly, the leading determinative factor in sexual differentiation of the gonads is the mesonephros, represented by the embryonic urinary system.     

No effects of estrogen receptor overexpression on gonadal sex differentiation and reversal in medaka fish

In order to elucidate a possible role of estrogen receptor in the gonadal sex differentiation and the sex reversal with sex steroids, we examined for the formation of testis or ovary in transgenic medaka fish overexpressing the medaka estrogen receptor under the constitutive medaka beta-actin promoter. The transgenic fish underwent the genetically determined gonadal differentiation and showed the same sex-reversal rates as those of wild-type non-transgenic fish after treatments with estrogen and androgen. These results present invaluable data to reconsider the role of estrogen receptor in the gonadal sex determination.     

鱼类性别与性别鉴定

性别分化和性别决定相互联系又有所区别,具双向潜力的未分化性腺经过程序性发生的一系列事件,发育成精巢或卵巢,并出现第二性征的过程称为性别分化,而性别决定则是确定性分化方向的方式。       

Sex determination and sex reversal

Sex determination in mammals is based on a genetic cascade that controls the fate of the gonads. Gonads will then direct the establishment of phenotypic sex through the production of hormones. Different types of sex reversal are expected to occur if mutations disrupt one of the three steps of gonadal differentiation: formation of the gonadal primordia, sex determination, and testis or ovary development.     

Wnt4 action in gonadal development and sex determination

Wnt4 is a growth factor involved in multiple developmental processes such as the formation of the kidney, adrenal, mammary gland, pituitary and the female reproductive system. During mammalian embryogenesis, Wnt4 is expressed in the gonads of both sexes before sex determination events take place and is subsequently down-regulated in the male gonad. Inactivation of the Wnt4 gene in mice has revealed that it is involved at several steps of female reproductive development. Wnt4 is implicated in Müllerian duct regression, the formation of sex-specific vasculature, the inhibition of steroidogenesis and in sex-specific cell migration events. A mouse model of sex-reversal has partially unravelled the molecular pathways in which Wnt4 operates during the development of the female reproductive system. However, the specific molecular mechanism of action of Wnt4 during gonadal development remains unknown. This and downstream signaling pathways involved in Wnt4 action during female gonad development are reviewed and models of Wnt4 action are proposed for Müllerian duct formation, sex-specific vasculature development, and sex determination events. Further identification of critical downstream effectors of the Wnt4 signaling pathway in mouse models and in patients with sex-reversal conditions could help in understanding sex-reversal pathologies in humans.     

Sex chromosomes and sex determination in reptiles

Reptiles occupy a crucial position with respect to vertebrate phylogeny, having roamed the earth for more than 300 million years and given rise to both birds and mammals. To date, this group has been largely ignored by contemporary genomics technologies, although the green anole lizard was recently recommended for whole genome sequencing. Future experiments using flow-sorted chromosome libraries and high-throughout genomic sequencing will help to discover important findings regarding sex chromosome evolution, early events in sex determination, and dosage compensation. This information should contribute extensively toward a general understanding of the genetic control of development in amniotes.     

Sex chromosomes, sex determination, and sex-linked sequences in Microtidae

The Arvicolidae is a widely distributed rodent group with several interesting characteristics in their sex chromosomes. Here, we summarize the actual knowledge of some of these characteristics. This mammalian group has species with abnormal sex determination systems. In fact, some species present the same karyotype in both males and females, with total absence of a Y chromosome, and hence of SRY and ZFY genes. Other species present fertile, sex-reversed XY females, generally due to mutations affecting X chromosomes. Furthermore, in Microtus oregoni males and females are gonosomic mosaic (the females are XO in the soma and XX in the germ cells, while the males are XY in the soma and OY in the germ cells). Regarding sex chromosomes, some species present enlarged (giant) sex chromosomes because of the presence of large blocks of constitutive heterochromatin, which have been demonstrated to be highly heterogeneous. Furthermore, we also consider the alterations affecting composition and localization of sex-linked genes or repeated sequences. Finally, this rodent group includes species with synaptic and asynaptic sex chromosomes. In fact, several species with asynaptic sex chromosomes have been described. It is interesting to note that within the genus Microtus both types of sex chromosomes are present.     

Glucose and pyruvate metabolism during mouse gonadal sex differentiation

In the mouse, gonadal sex differentiation starts around E12 and meiosis begins in the ovary shortly after E13. In the search for metabolic changes that might be correlated to gonadal sex differentiation and/or possibly the onset of meiosis, we investigated the metabolism of glucose and pyruvate in the developing mouse ovary before (E11.5-E12.5), during (E14.5-16.5), and after meiosis (E18.5), and in fetal testes without meiosis. Gonads were cultured with 14C-labeled glucose (0.02 and 5.58 mM) and 14C-pyruvate (0.17 mM). The oxidation expressed as 14CO2 production and the organification expressed as retention of 14C in the tissues were measured and correlated to the protein content of the gonads. Using 0.02 mM glucose, a decline in oxidation and organification was found in ovaries as well as in testes, which is probably related to starvation. Using 5.58 mM glucose, a continuous decline in oxidation was seen only in the testis. Organification of 0.17 mM pyruvate increased at E12.5 and E14.5 in the ovary but not in the testis. This was in despite of an exponential increase of protein content in the testes compared to only a moderate increase in the ovary. The CO2 production from 5.58 mM glucose was equal to that from 0.17 mM pyruvate in gonads of both sexes. In conclusion, an increased metabolism of 5.58 mM glucose and 0.17 mM pyruvate in the ovaries as compared to the testes is related to sex differences during gonadal formation and onset of meiosis in the ovaries. J. Exp. Zool. 288:130-138, 2001.     

Temperature-dependent sex determination in fish revisited: prevalence, a single sex ratio response pattern, and possible effects of climate change

Background

In gonochoristic vertebrates, sex determination mechanisms can be classified as genotypic (GSD) or temperature-dependent (TSD). Some cases of TSD in fish have been questioned, but the prevalent view is that TSD is very common in this group of animals, with three different response patterns to temperature.

Methodology/Principal Findings

We analyzed field and laboratory data for the 59 fish species where TSD has been explicitly or implicitly claimed so far. For each species, we compiled data on the presence or absence of sex chromosomes and determined if the sex ratio response was obtained within temperatures that the species experiences in the wild. If so, we studied whether this response was statistically significant. We found evidence that many cases of observed sex ratio shifts in response to temperature reveal thermal alterations of an otherwise predominately GSD mechanism rather than the presence of TSD. We also show that in those fish species that actually have TSD, sex ratio response to increasing temperatures invariably results in highly male-biased sex ratios, and that even small changes of just 1–2°C can significantly alter the sex ratio from 1∶1 (males∶females) up to 3∶1 in both freshwater and marine species.

Conclusions/Significance

We demonstrate that TSD in fish is far less widespread than currently believed, suggesting that TSD is clearly the exception in fish sex determination. Further, species with TSD exhibit only one general sex ratio response pattern to temperature. However, the viability of some fish populations with TSD can be compromised through alterations in their sex ratios as a response to temperature fluctuations of the magnitude predicted by climate change.     

蜜蜂性别决定与性比调控机理研究

叙述了 4个主要蜜蜂性别决定机理的假说 :即性位点假说、基因平衡假说、蜜蜂性别决定综合假说和性基因数量决定假说。然后就蜜蜂性比由蜂王操纵 ,或是由工蜂操纵进行了论述 ,并对蜜蜂性比调控机理研究提出了一些建议     

Sex chromosomes and sex determination in weird mammals

Weird mammals are of two types. Highly divergent mammals, such as the marsupials and monotremes, have informed us of the evolutionary history of the Y chromosome and sex-determining gene, and the recently specialized rodents can help us predict its future. The Y chromosome has had a short but eventful history, and is already heading briskly for oblivion. It originated as a homologous partner of the X when it acquired a sex-determining gene (not necessarily SRY). Most of the genes on the Y, even those with a male-specific function, evolved from genes now on the X. At the mercy of a high rate of variability and the forces of drift and selection, the Y has lost genes at a rate of 3-6 genes/million years, sparing those that acquired critical male-specific functions. Even these genes have disappeared from one mammalian lineage or another as their functions were usurped by genes elsewhere in the genome. The mammalian testis-determining gene, SRY, is a typical Y-borne gene. It arose by truncation of a gene (SOX3) on the X that is expressed in brain development, and it may work by interacting with (inhibiting?) related genes, including SOX9. Variant sex-determining systems in rodents show that the action of SRY can change, as it evidently has in the mouse, and SRY can be inactivated, as in akodont rodents, or even completely superseded, as in mole voles.     

人类性别决定和性别分化研究进展

SRY基因在人类性别分化中起着关键作用,目前研究认为SRY仅是涉及性别决定过程的基因之一,其他基因和SRY相关基因SOX9,抗副中肾激素基因AMH,编码缁类因子的基因SF1,X－连锁的DAX基因,wilm‘s肿瘤抑制基因WT1等基因都参与了人类性腺分化和发育,本文拟就人类性别决定基因的研究进展及其与人类性别分化的关系作一综述。