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[Genes involved in sex determination and differentiation].

Chromosomal sex is established at fertilization by the presence of an X or Y chromosome. The first step of male and female development is gonadal specialization in testes or ovaries; all other processes that follow result from secondary effects produced by testis and ovary hormones. Gonadal determination and differentiation and the development of external genitalia involve time- and tissue-specific expression of genes forming a gene cascade. Those genes, their expression profile and their role in the pathological manifestations related to gonadal and external genitalia development will be discussed in this review.

Animals↗

Yolk steroid hormones and sex determination in reptiles with TSD.

In reptiles with temperature-dependent sex determination (TSD), the temperature at which the eggs are incubated determines the sex of the offspring. The molecular switch responsible for determining sex in these species has not yet been elucidated. We have examined the dynamics of yolk steroid hormones during embryonic development in the snapping turtle, Chelydra serpentina, and the alligator, Alligator mississippiensis, and have found that yolk estradiol (E(2)) responds differentially to incubation temperature in both of these reptiles. Based upon recently reported roles for E(2) in modulation of steroidogenic factor 1, a transcription factor known to be significant in the sex differentiation process, we hypothesize that yolk E(2) is a link between temperature and the gene expression pathway responsible for sex determination and differentiation in at least some of these species. Here we review the evidence that supports our hypothesis.

Animals↗

Sex chromosomes and male functions: where do new genes go?

The position of a gene in the genome may have important consequences for its function. Therefore, when a new duplicate gene arises, its location may be critical in determining its fate. Our recent work in humans, mouse, and Drosophila provided a test by studying the patterns of duplication in sex chromosome evolution. We revealed a bias in the generation and recruitment of new gene copies involving the X chromosome that has been shaped largely by selection for male germline functions. The gene movement patterns we observed reflect an ongoing process as some of the new genes are very young while others were present before the divergence of humans and mouse. This suggests a continuing redistribution of male-related genes to achieve a more efficient allocation of male functions. This notion should be further tested in organisms employing other sex determination systems or in organisms differing in germline sex chromosome inactivation. It is likely that the selective forces that were detected in these studies are also acting on other types of duplicate genes. As a result, future work elucidating sex chromosome differentiation by other mutational mechanisms will shed light on this important process.

Animals↗

Maternal investment. Sex differences in avian yolk hormone levels.

It has been suggested that female birds put more resources into eggs fathered by attractive males by laying larger eggs or by adding more testosterone, but this inference could be undermined if eggs of different sex are provisioned differently, as these studies did not control for sex differences. Here we compare hormone concentrations in the yolks of male and female eggs and find that these are significantly different. Our results indicate that it is premature to conclude that female birds invest more in eggs sired by a preferred male, and raise the possibility that yolk sex steroids may be part of the sex-determining process in birds.

Animals↗

Genes expressed in the Drosophila head reveal a role for fat cells in sex-specific physiology.

The downstream effectors of the Drosophila sex determination cascade are mostly unknown and thought to mediate all aspects of sexual differentiation, physiology and behavior. Here, we employed serial analysis of gene expression (SAGE) to identify male and female effectors expressed in the head, and report 46 sex-biased genes (>4-fold/P < 0.01). We characterized four novel, male- or female-specific genes and found that all are expressed mainly in the fat cells in the head. Tsx (turn on sex-specificity), sxe1 and sxe2 (sex-specific enzyme 1/2) are expressed in males, but not females, and are dependent on the known sex determination pathway, specifically transformer (tra) and its downstream target doublesex (dsx). Female-specific expression of the fourth gene, fit (female-specific independent of transformer), is not controlled by tra and dsx, suggesting an alternative pathway for the regulation of some effector genes. Our results indicate that fat cells in the head express sex-specific effectors, thereby generating distinct physiological conditions in the male and female head. We suggest that these differences have consequences on the male and female brain by modulating sex-specific neuronal processes.

Adipocytes↗

The prototype of sex chromosomes found in Korean populations of Rana rugosa.

The seventh largest chromosome in Japanese populations of the frog Rana rugosa morphologically evolved as a sex chromosome. The sex chromosome is XX/XY type in one geographic form and ZZ/ZW type in another. In contrast, the seventh chromosomes are still homomorphic between the sexes in the other two geographic forms: they are more subtelocentric in the Kanto form and subtelocentric in the western Japanese form. To identify a prototype of the sex chromosomes, we extended our investigation in this study to the Korean form, which is supposed to be close to the phylogenetic origin of this species. The karyotype, a sex-linked gene sequence, and mechanisms of sex determination and gonadal differentiation were all examined. In addition, phylogenetic analyses were performed based on mitochondrial gene sequences and the results of crossings between the Korean and Japanese forms. As a consequence, the more subtelocentric seventh chromosome, shared by the Korean and Japanese Kanto forms, was concluded to be the prototype of the sex chromosomes. Starting at the prototype, a whole process of morphological sex chromosome evolution was reconstructed.

Animals↗

Interspecific hybridization between Oryzias latipes and Oryzias curvinotus causes XY sex reversal.

The teleost fish, Oryzias curvinotus, is a closely related species to the medaka, Oryzias latipes, and both species have the DMY gene, which is required for male development in O. latipes. It suggests that the molecular function of the DMY gene and the following molecular events of sex differentiation are conserved between these two species. In the present study, we obtained interspecific hybrids between O. curvinotus and O. latipes and demonstrated sex-reversed XY females in the hybrids. The incidence of sex-reversed females in F1 XY hybrids between O. curvinotus females and O. latipes males, and hybrids between O. latipes females and O. curvinotus males were 21% and 100%, respectively. These results indicate that DMY does not always determine maleness in hybrid fish even though it is able to specify normal male development on its native genetic background and suggest that there are some differences between DMY(latipes) and DMY(curvinotus) alleles. Appearance of XY females in F1 hybrids also suggests that an autosomal or X-liked gene(s) from the maternal species interferes in the function of the paternal DMY gene in the male-determining process of the hybrid fish. These hybrid fish would supply a new experimental approach for investigating the genetic and molecular pathway of testis determination and differentiation.

Animals↗

Changes in plasma and gonadal steroid hormones in relation to the reproductive cycle and the sex inversion process in the protandrous seabass, Lates calcarifer.

Plasma and gonadal levels of several gonadal steroids (testosterone, 11-ketotestosterone, androstenedione, 11 beta-hydroxyandrostenedione, 17 beta-estradiol, and estrone) were measured by RIA in the protandrous seabass, Lates calcarifer, throughout an annual reproductive cycle. Twenty to 25 fish were killed every month for gonadal and plasma sampling. Very low plasma levels of 11-ketotestosterone in females (monthly means always less than 75 pg/ml), and of 17 beta-estradiol (means always less than 68 pg/ml) and estrone (means always less than 42 pg/ml) in males did not fluctuate significantly during the cycle. Conversely, plasma concentrations of testosterone, estrone, and 17 beta-estradiol peaked during vitellogenesis in females (highest mean: 182 +/- 121, 182 +/- 32 and 598 +/- 369 pg/ml, respectively) and testosterone and 11-ketotestosterone peaked during spermiation in males (highest mean: 189 +/- 91 and 223 +/- 94 pg/ml, respectively). When sex type are compared over the whole cycle, females displayed higher 17 beta-estradiol (172 +/- 233.5 pg/ml) and estrone (79.5 +/- 72 pg/ml) levels than males (57 +/- 7.5 and 44 +/- 62.5 pg/ml, respectively), while males had higher 11-ketotestosterone levels (153 +/- 88 pg/ml) and, to a lesser extent, higher testosterone levels (128 +/- 82 pg/ml) than females (51.5 +/- 28 and 91.5 +/- 60 pg/ml, respectively). Transitional fish always exhibit low plasma levels for these four steroids (testosterone 56.5 +/- 12.5 pg/ml, 11-ketotestosterone 59 +/- 23.5 pg/ml, 17 beta-estradiol 65.6 +/- 36 pg/ml, and estrone 61 +/- 47.5 pg/ml). Among gonadal androgens, 11 beta-hydroxyandrostenedione predominated in testes (3.95 +/- 3 ng/g), except during spermiation (0.8 +/- 0.5 ng/g), and remained low in ovaries (1.05 +/- 1.4 ng/g). No differences were detected in gonads, for testosterone and 11-ketotestosterone whatever the sex type, but their concentrations were higher in vitellogenic and atretic ovaries. Androstenedione levels were slightly higher in testes (2.21 +/- 2 ng/g) than in ovaries (1.53 +/- 1.32 ng/g). Transitional gonads always showed low concentrations for these four androgens (testosterone 0.66 +/- 1.77 ng/g, 11-ketotestosterone 0.14 +/- 0.05 ng/g, androstenedione 0.3 +/- 0.34 ng/g, and 11 beta-hydroxyandrostenedione 0.2 +/- 0.23 ng/g). Gonadal 17 beta-estradiol was nearly undetectable in testes (0.06 +/- 0.07 ng/g), low in ovaries (0.42 +/- 0.46 ng/g), and strikingly high in transitional gonads (2.89 +/- 1.64 ng/g) even at the very beginning of sex inversion. This suggests an important role for this estrogen in the protandrous sex inversion process in the seabass L. calcarifer.

Animals↗

Sex predetermination and the ethics of sex selection.

At present there appear to be two main categories of problems involved in the ethics of sex selection. The first has to do with the status of the embryo, and the second has to do with the social consequences of making sex selection widely available. However, these may not be the only issues. There is growing evidence from evolutionary psychology and biology, which suggests that the sex of the offspring in mammals may not, after all, be a matter of chance. Instead, sex allocation in mammals may be the result of a finely tuned adaptive process involving the current suitability of a mother to conceive an offspring of a particular sex. If so, we need to know more about this process before embarking on a social policy that could have disadvantageous outcomes for children, their parents and society as a whole.

Animals↗

The Y chromosome and its role in testis differentiation and spermatogenesis.

The Y chromosome contains genes and gene families that play critical roles in the processes of testis determination and testis differentiation. Great strides have been made toward defining the genetic pathways associated with the determination of gender. The data are summarized and discussed and clinical ramifications are considered.

Cell Differentiation↗

In ovo exposure to o,p -DDE affects sexual development but not sexual differentiation in Japanese medaka (Oryzias latipes).

Despite being banned in many countries, dichlorodiphenyltrichloroethane (DDT) and its metabolites dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD) continue to be found in fish tissues at concentrations of concern. Like o,p -DDT, o,p -DDE is estrogenic and is believed to exert its effects through binding to the estrogen receptor. The limited toxicologic data for o,p -DDE suggest that it decreases fecundity and fertility of fishes. We conducted an egg injection study using the d-rR strain of medaka and environmentally relevant concentrations of o,p -DDE to examine its effects on sexual differentiation and development. The gonads of exposed fish showed no evidence of sex reversal or intersex. However, other gonad abnormalities occurred in exposed individuals. Females exhibited few vitellogenic oocytes and increased atresia. Male testes appeared morphologically normal but were very small. Gonadosomatic index values for both sexes were lower for exposed fish. Our observations of abnormal female and very small male gonads after in ovo o,p -DDE exposure may be indicative of effects on early endocrine processes important for normal ovarian and testicular development.

Animals↗