Regulation of male sex determination: genital ridge formation and Sry activation in mice

Sex determination is essential for the sexual reproduction to generate the next generation by the formation of functional male or female gametes. In mammals, primary sex determination is commenced by the presence or absence of the Y chromosome, which controls the fate of the gonadal primordium. The somatic precursor of gonads, the genital ridge is formed at the mid-gestation stage and gives rise to one of two organs, a testis or an ovary. The fate of the genital ridge, which is governed by the differentiation of somatic cells into Sertoli cells in the testes or granulosa cells in the ovaries, further determines the sex of an individual and their germ cells. Mutation studies in human patients with disorders of sex development and mouse models have revealed factors that are involved in mammalian sex determination. In most of mammals, a single genetic trigger, the Y-linked gene Sry (sex determination region on Y chromosome), regulates testicular differentiation. Despite identification of Sry in 1990, precise mechanisms underlying the sex determination of bipotential genital ridges are still largely unknown. Here, we review the recent progress that has provided new insights into the mechanisms underlying genital ridge formation as well as the regulation of Sry expression and its functions in male sex determination of mice.     

An overview of factors influencing sex determination and gonadal development in birds

The morphological development of the embryonic gonads is very similar in birds and mammals, and recent evidence suggests that the genes involved in this process are conserved between these classes of vertebrates. The genetic mechanism by which sex is determined in birds remains to be elucidated, although recent studies have reinforced the contention that steroids may play an important role in the structural development of the testes and ovaries in birds. So far, few genes have been assigned to the avian sex chromosomes, but it is known that the Z and W chromosomes do not share significant homology with the mammalian X and Y chromosomes. The commercial importance of poultry breeding has motivated considerable investment in developing physical and genetic maps of the chicken genome. These efforts, in combination with modern molecular approaches to analyzing gene expression, should help to elucidate the sex-determining mechanism in birds in the near future.     

Sex determining mechanisms: an evolutionary perspective

Theories on the evolution of sex determining mechanisms are reviewed for male and female heterogamety, environmental sex determination, and briefly, haplo-diploidy and hermaphroditism. Because of their discrete and well-defined nature, sex determining mechanisms lend themselves to three types of evolutionary questions: what variety occurs and might be expected but does not occur, how do changes occur from one mechanism to another, and why do certain changes occur? All three approaches were illustrated for these different sex determining mechanisms. A generality emerging from these studies is that, at the level of selection of the sex ratio, there are no intrinsic problems in evolving from one sex determining mechanism to another: straightforward transitions between different mechanisms exist under various conditions.     

Endocrine and environmental aspects of sex differentiation in fish

This paper reviews the current knowledge concerning the endocrine and environmental regulations of both gonadal sex differentiation in gonochoristic and sex inversion in hermaphroditic fish. Within the central nervous system, gonadotropins seem to play a role in triggering sex inversion in hermaphroditic fish. In gonochorists, although potentially active around this period, the hypothalamo-pituitary axis is probably not involved in triggering sex differentiation. Although steroids and steroidogenic enzymes are probably not the initial triggers of sex differentiation, new data, including molecular approaches, have confirmed that they are key physiological steps in the regulation of this process. Environmental factors can strongly influence sex differentiation and sex inversion in gonochoristic and hermaphroditic fish, respectively. The most important environmental determinant of sex would appear to be temperature in the former species, and social factors in the latter. Interactions between environmental factors and genotype have been suggested for both gonochoristic and hermaphroditic fish.     

Sex determining mechanisms: An evolutionary perspective

Summary Theories on the evolution of sex determining mechanisms are reviewed for male and female heterogamety, environmental sex determination, and briefly, haplo-diploidy and hermaphroditism. Because of their discrete and well-defined nature, sex determining mechanisms lend themselves to three types of evolutionary questions:what variety occurs and might be expected but does not occur,how do changes occur from one mechanism to another, andwhy do certain changes occur? All three approaches were illustrated for these different sex determining mechanisms. A generality emerging from these studies is that, at the level of selection on the sex ratio, there are no intrinsic problems in evolving from one sex determining mechanism to another: straightforward transitions between different mechanisms exist under various conditions.     

Further chromosomal studies on Ellobius lutescens: heteromorphism of chromosome No. 1 is not associated with sex determination

Twelve animals of the species Ellobius lutescens from two generations were studied with various chromosomal banding techniques. This species carries 17 chromosomes in both sexes. In preceding studies chromosomal sex determination was assigned to different structural variants of chromosome No. 1. In the present study, no definite chromosomal basis for sex determination was found.     

Effect of sex hormones on uric acid metabolism in rats.

The effects of sex hormones on purine metabolism were investigated in rats. No influence on purine synthesis was shown by the injection of estrogen and androgen. The plasma urate levels were significantly lowered from 2.43 +/- 1.04 mg/100 ml to 1.53 +/- 0.57 mg/100 ml by the injection of progesterone. Urinary excretion of uric acid plus allantoin was slightly reduced. These results suggested that progesterone may influence age and sex differences in human plasma urate levels.     

Body size regulation and insulin-like growth factor signaling

How animals achieve their specific body size is a fundamental, but still largely unresolved, biological question. Over the past decades, studies on the insect model system have provided some important insights into the process of body size determination and highlighted the importance of insulin/insulin-like growth factor signaling. Fat body, the Drosophila counterpart of liver and adipose tissue, senses nutrient availability and controls larval growth rate by modulating peripheral insulin signaling. Similarly, insulin-like growth factor I produced from liver and muscle promotes postnatal body growth in mammals. Organismal growth is tightly coupled with the process of sexual maturation wherein the sex steroid hormone attenuates body growth. This review summarizes some important findings from Drosophila and mammalian studies that shed light on the general mechanism of animal size determination.     

Molecular mechanisms in male determination and germ cell differentiation

Sex determination and gametogenesis are key processes in human reproduction, and any defect can lead to infertility. We describe here the molecular mechanisms of male sex determination and testis formation; defects in sex determination lead to a female phenotype despite the presence of a Y chromosome, more rarely to a male phenotype with XX chromosomes, or to intersex phenotypes. Interestingly, these phenotypes are often associated with other developmental malformations. In testis, spermatozoa are produced from renewable stem cells in a complex differentiation process called spermatogenesis. Gene expression during spermatogenesis differs to a surprising degree from gene expression in somatic cells, and we discuss here mechanistic differences and their effect on the differentiation process and male fertility.Received 23 January 2004; received after revision 30 March 2004; accepted 6 April 2004     

Instances of sex inversion in the domesticated swordtail, Xiphophorus helleri Heckel (Pisces, Osteichthyes)

3 protogynous hermaphrodites were found in a domesticated strain of Xiphophorus helleri, confirming much doubted observations by older authors. It therefore seems that sex determination may vary between strains, certain strains being strictly gonochoristic but others being capable of true hermaphroditism.     

Invariability of the H-Y antigen expression in the heterogametic sex of some amphbians and evidence for sexual dimophrism of the antigen expression in Pelodytes punctatus D (Amphibia, Anura)]

The H-Y antigen is studied in some Amphibians whose sexual genetic constitution is known. Thus, in Pelurodeles waltlii, Ambystoma mexicanum, Xenopus laevis and Rana ridibunda, the invariability of the H-Y antigen expression in the heterogametic, sex is confirmed. In Pelodytes punctatus the genetic sex is unknown but the existence of the H-Y antigen in phenotypic males leads to the conclusion of a male heterogamety of the XY type.     

Instances of sex inversion in the domesticated swordtail,Xiphophorus helleri heckel (pisces,osteichthyes)

Summary 3 protogynous hermaphrodites were found in a domesticated strain ofXiphophorus helleri, confirming much doubted observations by older authors. It therefore seems that sex determination may vary between strains, certain strains being strictly gonochoristic but others being capable of true hermaphroditism.     

Karyotype and chromosome banding in the reed frogHyperolius viridiflavus ommatostictus (Amphibia,Anura, Hyperoliidae)

Summary C-banding and mithramycin staining were used to characterize the karyotypes of 10 specimens of the African reed frogHyperolius viridiflavus ommatostictus from Tanzania. The diploid chromosome number is 2n=24. Although no heteromorphic sex chromosomes were present in the mitotic karyotypes, in many diakineses of male meiosis one or two bivalents exhibited an end-to-end arrangement. In the laboratory 7 out of 24 females changed sex spontaneously. This indicates that an XY/XX system of sex determination operates inH. viridiflavus ommatostictus.This study was supported by the Deutsche Forschungsgemeinschaft (Schm 484/2-4). We thank K. E. Linsenmair and C. M. Richards for helpful comments on an earlier draft.     

A frog with highly evolved sex chromosomes

Summary Highly differentiated ZZ/ZW sex chromosomes and an exceptionally low genome, size were found in the karyotypes ofPyxicephalus adspersus (Anura, Ranidae). The W-chromosome is considerably smaller than the Z-chromosome and consists to a very great proportion of constitutive heterochromatin. The DNA content of this species and the chromosome length have the lowest values determined in the Ranidae to date.This study was supported by a grant from the Deutsche Forschungsgemeinschaft. We thank Professor W. Engel for his support and interest.     

Patterns in plant parthenogenesis

Summary Plant taxa that reproduce asexually display some distinct geographical and ecological patterns. A literature review reveals that such taxa 1) tend to have larger ranges, 2) tend to range into higher latitudes, and 3) tend to range to higher elevations than do their sexual relatives. Asexual taxa have a greater tendency than sexual taxa do to colonize once-glaciated areas. These trends have previously been identified as characteristic of parthenogenetic animals as well. While many authors have interpreted these trends as providing support for the biotic uncertainty hypothesis for the maintenance of sex, these trends are consistent with several other interpretations as well. Furthermore, all of these interpretations have ignored the positive correlation that exists between ploidy level and breeding system: asexual plant and animal taxa are generally polyploid, while their sexual relatives are generally diploid. Evidence is presented for plants, and by extension for animals as well, that high ploidy levels alone could (independent of breeding system) endow individuals with the ability to tolerate these extreme environments. For this reason, it appears premature to interpret observed distribution patterns as evidence to support hypotheses about what forces maintain sexual reproduction. Only experimental tests, using sexuals and asexuals of comparable ploidy levels, can permit us to discriminate among the alternatives.     

Chiral influence of sex pheromonal substances on responses of the male American cockroach

Summary In order to elucidate the roles of optical enantiomers of sex pheromonal substances of the American cockroach, behavioral assays with a single enantiomer and with mixtures of enantiomers of sex pheromone mimics were carried out. Inactive enantiomers [(–)-enantiomers] had no influence on the potency of enantiomers active as sex pheromones [(+)-enantiomers]. By analysis of the results from EAG recordings with single and mixed sample of the enantiomers, it was confirmed that (–)-enantiomers did not react with the sex pheromone receptors which are responsive to (+)-enantiomers.We acknowledge technical assistance from Miss R. Kimura.     

Karyotype and chromosome banding in the reed frog Hyperolius viridiflavus ommatostictus (Amphibia, Anura, Hyperoliidae)

C-banding and mithramycin staining were used to characterize the karyotypes of 10 specimens of the African reed frog Hyperolius viridiflavus ommatostictus from Tanzania. The diploid chromosome number is 2n = 24. Although no heteromorphic sex chromosomes were present in the mitotic karyotypes, in many diakineses of male meiosis one or two bivalents exhibited an end-to-end arrangement. In the laboratory 7 out of 24 females changed sex spontaneously. This indicates that an XY/XX system of sex determination operates in H. viridiflavus ommatostictus.     

Der Einfluß der Temperatur auf die Giftwirkung des DDT bei Honigbienen (Apis mellifica L.)

Summary The action of DDT on honey-bees depends to a high extent on the temperature (see graph). At 36°C (breeding temperature) DDT has a far weaker insecticidal action than at 20°C (laboratory temperature). This shows that the insecticidal properties of DDT diminish with the raise of temperature.This resistance to DDT at higher temperature is most propitious for bee-keeping and also explains the fact why in agricultural practice there has been no corroborated case of poisoning of bees, though in laboratory tests DDT avered itself to be toxic to bees.