Genetic control of spermatogenesis and sex determination in mammals

The material was analyzed on the main problems of genetics of mammalian spermatogenesis, sex determination, its reversion and other defects from the standpoint of current cytological and molecular-genetic concepts of functional activity of the parental genomes after fertilization and behavior of their chromosomes at the early embroyonic stages. On the basis of this analysis, a hypothesis has been proposed, which explains a high percentage (50% or more) of early embryonic mortality in placental mammals under the conditions of natural and extracorporeal fertilization, as well as regular appearance of defects in the course of natural sex determination, including the appearance of representatives of both sex minorities. We do not make pretense to comprehensive and deep analysis of male gametogenesis and sex determination in mammals.     

Genetic evidence for co-occurrence of chromosomal and thermal sex-determining systems in a lizard

An individual's sex depends upon its genes (genotypic sex determination or GSD) in birds and mammals, but reptiles are more complex: some species have GSD whereas in others, nest temperatures determine offspring sex (temperature-dependent sex determination). Previous studies suggested that montane scincid lizards (Bassiana duperreyi, Scincidae) possess both of these systems simultaneously: offspring sex is determined by heteromorphic sex chromosomes (XX-XY system) in most natural nests, but sex ratio shifts suggest that temperatures override chromosomal sex in cool nests to generate phenotypically male offspring even from XX eggs. We now provide direct evidence that incubation temperatures can sex-reverse genotypically female offspring, using a DNA sex marker. Application of exogenous hormone to eggs also can sex-reverse offspring (oestradiol application produces XY as well as XX females). In conjunction with recent work on a distantly related lizard taxon, our study challenges the notion of a fundamental dichotomy between genetic and thermally determined sex determination, and hence the validity of current classification schemes for sex-determining systems in reptiles.     

BioEssays 10/2020

Frequent independent origins of environmental sex determination (ESD) are assumed within amniotes. However, the phylogenetic distribution of sex-determining modes suggests that ESD is likely very ancient and may be homologous across ESD groups. Sex chromosomes are demonstrated to be old and stable in endothermic (mammals and birds) and many ectothermic (non-avian reptiles) lineages, but they are mostly non-homologous between individual amniote lineages. The phylogenetic pattern may be explained by ancestral ESD with multiple transitions to later evolutionary stable genotypic sex determination. It is pointed out here that amniote ESD shares several key aspects with sequential hermaphroditism of fishes such as a lack of sex differences in genomes, biased population sex ratios, and potentially also molecular mechanism related to general stress responses. Here, it is speculated that ESD evolves via a heterochronic shift of the sensitive period of sex change from the adult to the embryonic stage in a hermaphroditic amniote ancestor. Also see the video abstract here https://youtu.be/q2mjtlCefu4 .     

Long-lasting fitness consequences of prenatal sex ratio in a viviparous lizard

Maternal effects and early environmental conditions are important in shaping offspring developmental trajectories. For example, in laboratory mammals, the sex ratio during gestation has been shown to influence fitness-related traits via hormonal interaction between fetuses. Such effects have the potential to shape, or constrain, many important aspects of the organism's life, but their generality and importance in natural populations remain unknown. Using long-term data in a viviparous lizard, Lacerta vivipara, we investigated the relationship between prenatal sex ratio and offspring growth, survival, and reproductive traits as adults. Our results show that females from male-biased clutches grow faster, mature earlier, but have lower fecundity than females from female-biased clutches. Furthermore, male reproduction was also affected by the sex ratio during embryonic development, with males from male-biased clutches being more likely to successfully reproduce at age one than males from female-biased clutches. Thus, the sex ratio experienced during gestation can have profound and long-lasting effects on fitness in natural populations of viviparous animals, with important implications for life-history evolution and sex allocation.     

Environmental sex reversal,Trojan sex genes,and sex ratio adjustment: conditions and population consequences

The great diversity of sex determination mechanisms in animals and plants ranges from genetic sex determination (GSD, e.g. mammals, birds, and most dioecious plants) to environmental sex determination (ESD, e.g. many reptiles) and includes a mixture of both, for example when an individual’s genetically determined sex is environmentally reversed during ontogeny (ESR, environmental sex reversal, e.g. many fish and amphibia). ESD and ESR can lead to widely varying and unstable population sex ratios. Populations exposed to conditions such as endocrine‐active substances or temperature shifts may decline over time due to skewed sex ratios, a scenario that may become increasingly relevant with greater anthropogenic interference on watercourses. Continuous exposure of populations to factors causing ESR could lead to the extinction of genetic sex factors and may render a population dependent on the environmental factors that induce the sex change. However, ESR also presents opportunities for population management, especially if the Y or W chromosome is not, or not severely, degenerated. This seems to be the case in many amphibians and fish. Population growth or decline in such species can potentially be controlled through the introduction of so‐called Trojan sex genes carriers, individuals that possess sex chromosomes or genes opposite from what their phenotype predicts. Here, we review the conditions for ESR, its prevalence in natural populations, the resulting physiological and reproductive consequences, and how these may become instrumental for population management.     

哺乳动物性别决定和性反转

目前已知SRY仅是涉及性别决定过程的基因之一.近年来又发现和克隆了许多可能参与性腺分化与发育的基因,如副中肾抑制基因MIS,也称抗副中肾激素基因AMH;SRY相关基因SOX9;编码甾类因子的基因SFI;X-连锁的DAX基因;Wilm′s肿瘤抑制基因WTI;以及X-连锁的剂量敏感基因DSS等,并新建立了性别决定的Z-基因模型,DSS-基因模型和Jimenez等的模型,较合理地解释了哺乳动物性别决定的分子机理和以前难以解释的各种奇特的性反转现象,使性别决定的研究取得了长足的进展,但仍有一些悬而未决的问题有待于进一步探索.     

Insights into epigenetic patterns in mammalian early embryos

Mammalian fertilization begins with the fusion of two specialized gametes,followed by major epigenetic remodeling leading to the formation of a totipotent embryo.During the development of the pre-implantation embryo,precise reprogramming progress is a prerequisite for avoiding developmental defects or embryonic lethality,but the underlying molecular mechanisms remain elusive.For the past few years,unprecedented breakthroughs have been made in mapping the regulatory network of dynamic epigenomes during mammalian early embryo development,taking advantage of multiple advances and innovations in low-input genome-wide chromatin analysis technologies.The aim of this review is to highlight the most recent progress in understanding the mechanisms of epigenetic remodeling during early embryogenesis in mammals,including DNA methylation,histone modifications,chromatin accessibility and 3D chromatin organization.     

早期胚胎的发育选择:性别决定

性别决定是一个复杂的发育调控过程, 早期胚胎发育过程中, 雌雄二者必居其一的发育选择是胚胎性腺形成必须的发育决定。文章综述了动物性别决定的遗传系统、性腺发生、性别决定关键基因及其作用机制, 从分子进化的角度分析了性染色体与性别决定形成机制, 提示性别决定基因在进化中总是趋向异配性染色体。     

Sex-related differences in developmental rates of bovine embryos produced and cultured in vitro.

The classical concept of sex determination in mammals is that a Y chromosomal gene controls the development of the indifferent gonad into a testis. Subsequent divergence of sexual phenotypes is secondary to this gonadal determination. The most likely candidate gene is SRY (sex-determining region Y) in humans, and Sry in mouse. However, several lines of evidence indicate that sexual dimorphism occurs even before the indifferent gonad appears. Here we present evidence that bovine male embryos generally develop to more advanced stages than do females during the first 8 days after insemination in vitro. Corresponding relationships between both cell numbers and mitotic indices and sex were also seen. Although it is not clear whether this phenomenon involves factors originating before or after fertilization, these findings suggest that sex-related gene expression affects the development of embryos soon after activation of the embryonic genome and well before gonadal differentiation.     

Sex determination in the chicken embryo.

The chicken embryo represents a suitable model for studying vertebrate sex determination and gonadal sex differentiation. While the basic mechanism of sex determination in birds is still unknown, gonadal morphogenesis is very similar to that in mammals, and most of the genes implicated in mammalian sex determination have avian homologues. However, in the chicken embryo, these genes show some interesting differences in structure or expression patterns to their mammalian counterparts, broadening our understanding of their functions. The novel candidate testis-determining gene in mammals, DMRT1, is also present in the chicken, and is expressed specifically in the embryonic gonads. In chicken embryos, DMRT1 is more highly expressed in the gonads and Müllerian ducts of male embryos than in those of females. Meanwhile, expression of the orphan nuclear receptor, Steroidogenic Factor 1 (SF1) is up-regulated during ovarian differentiation in the chicken embryo. This contrasts with the expression pattern of SF1 in mouse embryos, in which expression is down-regulated during female differentiation. Another orphan receptor initially implicated in mammalian sex determination, DAX1, is poorly conserved in the chicken. A chicken DAX1 homologue isolated from a urogenital ridge library lacked the unusual DNA-binding motif seen in mammals. Chicken DAX1 is autosomal, and is expressed in the embryonic gonads, showing somewhat higher expression in female compared to male gonads, as in mammals. However, expression is not down-regulated at the onset of testicular differentiation in chicken embryos, as occurs in mice. These comparative data shed light on vertebrate sex determination in general.     

Female turtles from hot nests: is it duration of incubation or proportion of development at high temperatures that matters?

Summary Mean daily temperature in natural nests of freshwater turtles with temperature-dependent sex determination is known to be a poor predictor of hatchling sex ratios when nest temperatures fluctuate. To account for this, a model was developed on the assumption that females will emerge from eggs when more than half of embryonic development occurs above the threshold temperature for sex determination rather than from eggs that spend more than half their time above the threshold. The model is consistent with previously published data and in particular explains the phenomenon whereby the mean temperature that best distinguishes between male and female nests decreases with increasing variability in nest temperature. The model, if verified by controlled experiments, has important implications for our understanding of temperature-dependent sex determination in natural nests. Both mean nest temperature and hours spent above the threshold will be poor predictors of hatchling sex ratios. Studies designed to investigate latitudinal trends and inter-specific differences in the threshold temperature will need to consider latitudinal and inter-specific variation in the magnitude of diel fluctuations in nest temperature, and variation in factors influencing the magnitude of those fluctuations, such as nest depth. Furthermore, any factor that modifies the relationship between developmental rate and temperature can be expected to influence hatchling sex ratios in natural nests, especially when nest temperatures are close to the threshold.     

Evolutionary transitions between mechanisms of sex determination in vertebrates

Sex in many organisms is a dichotomous phenotype--individuals are either male or female. The molecular pathways underlying sex determination are governed by the genetic contribution of parents to the zygote, the environment in which the zygote develops or interaction of the two, depending on the species. Systems in which multiple interacting influences or a continuously varying influence (such as temperature) determines a dichotomous outcome have at least one threshold. We show that when sex is viewed as a threshold trait, evolution in that threshold can permit novel transitions between genotypic and temperature-dependent sex determination (TSD) and remarkably, between male (XX/XY) and female (ZZ/ZW) heterogamety. Transitions are possible without substantive genotypic innovation of novel sex-determining mutations or transpositions, so that the master sex gene and sex chromosome pair can be retained in ZW-XY transitions. We also show that evolution in the threshold can explain all observed patterns in vertebrate TSD, when coupled with evolution in embryonic survivorship limits.     

Sex determination and differentiation in organisms other than higher plants

The understanding of sex determination in general, but in particular in mammals, has been a subject of scientific speculation for a long time. It has been shown that in many vertebrate and invertebrate species, the sex of an individual is determined by the individual's chromosomal constitution. Initial studies of classical genetic searching for sex-transforming mutations and the scrupulous analyses of modified phenotypes have shed light on the mechanism(s) of sex-determination. They paved the road to successful studies at molecular level. After a brief review on sex determination in chosen model species, the “Drosophila system” is presented to exemplify a possible general principle for sex determinism.     

Evidence of thermolabile sex determination in pejerrey*

Temperature regimes of 17 ± 1°C and 21 ±1°C early in development of pejerrey Odontesthes bonariensis produced nearly all females, whereas at 25 ± 1°C variable, sometimes male-biased sex-ratios were obtained. The critical period of thermolabile sex determination seemed to occur between 25 and 50 days post-hatch (about 11 and 21 mm s.i.) at low temperatures (17–20°C) and between 0 and 25 days (about 7 and 15 mm) at high temperatures (22–25°C). The likelihood of expression of temperature-dependent sex determination in natural populations and the possible adaptive significance of environmental sex determination in pejerrey are discussed.     

Nonautonomous sex determination controls sexually dimorphic development of the Drosophila gonad

Sex determination in Drosophila is commonly thought to be a cell-autonomous process, where each cell decides its own sexual fate based on its sex chromosome constitution (XX versus XY). This is in contrast to sex determination in mammals, which largely acts nonautonomously through cell-cell signaling. Here we examine how sexual dimorphism is created in the Drosophila gonad by investigating the formation of the pigment cell precursors, a male-specific cell type in the embryonic gonad. Surprisingly, we find that sex determination in the pigment cell precursors, as well as the male-specific somatic gonadal precursors, is non-cell autonomous. Male-specific expression of Wnt2 within the somatic gonad triggers pigment cell precursor formation from surrounding cells. Our results indicate that nonautonomous sex determination is important for creating sexual dimorphism in the Drosophila gonad, similar to the manner in which sex-specific gonad formation is controlled in mammals.     

What was the ancestral sex‐determining mechanism in amniote vertebrates?

Amniote vertebrates, the group consisting of mammals and reptiles including birds, possess various mechanisms of sex determination. Under environmental sex determination (ESD), the sex of individuals depends on the environmental conditions occurring during their development and therefore there are no sexual differences present in their genotypes. Alternatively, through the mode of genotypic sex determination (GSD), sex is determined by a sex‐specific genotype, i.e. by the combination of sex chromosomes at various stages of differentiation at conception. As well as influencing sex determination, sex‐specific parts of genomes may, and often do, develop specific reproductive or ecological roles in their bearers. Accordingly, an individual with a mismatch between phenotypic (gonadal) and genotypic sex, for example an individual sex‐reversed by environmental effects, should have a lower fitness due to the lack of specialized, sex‐specific parts of their genome. In this case, evolutionary transitions from GSD to ESD should be less likely than transitions in the opposite direction. This prediction contrasts with the view that GSD was the ancestral sex‐determining mechanism for amniote vertebrates. Ancestral GSD would require several transitions from GSD to ESD associated with an independent dedifferentiation of sex chromosomes, at least in the ancestors of crocodiles, turtles, and lepidosaurs (tuataras and squamate reptiles). In this review, we argue that the alternative theory postulating ESD as ancestral in amniotes is more parsimonious and is largely concordant with the theoretical expectations and current knowledge of the phylogenetic distribution and homology of sex‐determining mechanisms.     

Phylogeny of sex‐determining mechanisms in squamate reptiles: are sex chromosomes an evolutionary trap?

Squamate reptiles possess two general modes of sex determination: (1) genotypic sex determination (GSD), where the sex of an individual is determined by sex chromosomes, i.e. by sex‐specific differences in genotype; and (2) temperature‐dependent sex determination (TSD), where sex chromosomes are absent and sex is determined by nongenetic factors. After gathering information about sex‐determining mechanisms for more than 400 species, we employed comparative phylogenetic analyses to reconstruct the evolution of sex determination in Squamata. Our results suggest relative uniformity in sex‐determining mechanisms in the majority of the squamate lineages. Well‐documented variability is found only in dragon lizards (Agamidae) and geckos (Gekkota). Polarity of the sex‐determining mechanisms in outgroups identified TSD as the ancestral mode for Squamata. After extensive review of the literature, we concluded that to date there is no known well‐documented transition from GSD to TSD in reptiles, although transitions in the opposite direction are plentiful and well corroborated by cytogenetic evidence. We postulate that the evolution of sex‐determining mechanisms in Squamata was probably restricted to the transitions from ancestral TSD to GSD. In other words, transitions were from the absence of sex chromosomes to the emergence of sex chromosomes, which have never disappeared and constitute an evolutionary trap. This evolutionary trap hypothesis could change the understanding of phylogenetic conservatism of sex‐determining systems in many large clades such as butterflies, snakes, birds, and mammals. © 2009 The Linnean Society of London, Zoological Journal of the Linnean Society, 2009, 156 , 168–183.     

Co-occurrence of multiple, supposedly incompatible modes of sex determination in a lizard population

Sex is determined genetically in some species (genotypic sex determination, or GSD) and by the environment (environmental sex determination, or ESD) in others. The two systems are generally viewed as incompatible alternatives, but we have found that sex determination in a species of montane lizard ( Bassiana duperreyi , Scincidae) in south-eastern Australia is simultaneously affected by sex chromosomes and incubation temperatures, as well as being related to egg size. This species has strongly heteromorphic sex chromosomes, and yet incubation at thermal regimes characteristic of cool natural nests generates primarily male offspring. We infer that incubation temperatures can over-ride genetically determined sex in this species, providing a unique opportunity to explore these alternative sex-determining systems within a single population.     

Parental control of sex ratio in Gammarus duebeni,an organism with environmental sex determination

Parental sex ratio control was investigated in Gammarus duebeni, an amphipod with an environmentally mediated sex determining system. The effect on the F2 generation sex ratio of the photoperiodic conditions experienced by a) the P generation during and after copulation, b) the F1 generation before and after sex determination, and c) the F2 generation themselves during the period of sex determination, was tested. The photoperiodic conditions the F2 generation experienced during the period of sex determination had a significant effect on their sex ratio (more males were produced under long-day than under short-day conditions), but the photoperiodic conditions experienced by the F1 generation males and females or the P generation on the F1 male's side had no effect on the F2 sex ratio. However, the photoperiodic conditions the P generation on the F1 female's side experienced significantly affected the F2 sex ratio. When these animals experienced long-day conditions the F2 generation became female biased and when they experienced short-day conditions, male biased. It is proposed that the mechanism of control operates through the F1 generation mothers whilst in an embryonic stage of development in the P generation mother's brood pouch. The photoperiodically mediated effects of the embryonic F1 generation mother and the F2 generation on sex determination are additive. A mechanism by which both F1 generation maternal and F2 generation sex ratio control could operate in the field is proposed.