Function of the Sex Chromosomes in Mammalian Fertility

Heard, Edith; Turner, James M. A.

doi:10.1101/cshperspect.a002675

Cited by 60 publications

(62 citation statements)

References 135 publications

(150 reference statements)

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“…in the pseudoautosomal region), and are therefore present at reduced levels in Turner patients compared to normal males and females. Interestingly, XO mice show no phenotype except for being infertile [16]. This is probably due to the fact that far fewer genes escape XCI in mice ($3%) compared to humans ($15%) and also because the human X carries more pseudoautosomal genes than the mouse X chromosome [17,18].…”

mentioning

confidence: 93%

“…Some behavioral symptoms of Turner patients are specific to cases where the paternal or the maternal X is present, suggesting a role of imprinted genes on the X. While Turner syndrome is associated with reduced levels of escape genes, the XXY Klinefelter syndrome presumably results from increased levels and manifests itself by tall stature, infertility and behavioral abnormalities [16]. Surprisingly, symptoms due to increased X-chromosome copy number are more severe in the male XXY context.…”

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confidence: 97%

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Role and control of X chromosome dosage in mammalian development

Schulz¹,

Heard²

2013

Current Opinion in Genetics & Development

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Many species have evolved sex chromosomes with highly divergent gene content, such as the X and Y chromosomes in mammals. As most non sex-specific genes probably need to be expressed at similar levels in males and females, dosage compensation mechanisms are in place to equalize the gene dosage between the sexes, and possibly also between sex chromosomes and autosomes. In mammals, one out of two X chromosomes is inactivated early during development in a process called X-chromosome inactivation that has been investigated intensively in the 50 years since it was discovered. Less is known about the potential functional roles of X-linked gene dosage, for example in controlling development in a sexspecific manner. In this review, we discuss the evolution of dosage compensation and how it is controlled during embryogenesis of mammals. In addition we will summarize evidence on the potential role of X chromosome number during early development. IntroductionIn many species, sex is determined by sex chromosome composition, such as XY and XX in male and female mammals. The X and Y chromosomes presumably evolved from a pair of autosomes, one of which (the proto-Y) acquired a sex determining gene and subsequently accumulated male beneficial genes. To permanently link these genes to the male sex, the Y chromosome had to cease recombining with the X during meiosis, and this facilitated a progressive loss of Y-linked genes (reviewed in [1]). Therefore for most X-linked genes, only one copy remains, on the X, and this creates a dosage imbalance, both with respect to interacting autosomal genes and between the sexes (XX versus XY). To resolve this dosage imbalance, a variety of dosage compensation mechanisms have evolved (reviewed in [2]). The first step in compensating the loss of Y-linked genes is probably the upregulation of their Xlinked homologs (Ohno's hypothesis [3]). In the wellstudied example of Drosophila this upregulation is restricted to males, thereby restoring both dosage equality between the X chromosome and autosomes, as well as between the sexes. In contrast, worms (Caenorhabditis elegans) and mammals are thought to upregulate the X chromosome in both sexes and therefore require additional mechanisms to balance X-linked gene dosage between males and females. To achieve this, worms downregulate both X's in hermaphrodites (XX), while mammals, on which we focus in this review, silence one of the two X chromosomes in each female cell in a process called Xchromosome inactivation (XCI). Albeit widespread, the extent of dosage compensation between the sexes varies considerably among species. In birds for example, dosage compensation of Z-linked genes is only partial, as males (ZZ) express 1.2-1.4-fold higher levels compared to females (ZW) [2].Although in mammals, dosage compensation for most genes on the X is probably vital, dosage differences might also play a functional role at several levels. In particular, genes that escape X inactivation are thought to contribute to the phenotypic differences between the sexes [4]...

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confidence: 93%

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confidence: 97%

Role and control of X chromosome dosage in mammalian development

Schulz¹,

Heard²

2013

Current Opinion in Genetics & Development

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“…Meiosis in males with X-autosome translocations is typically affected due to failure in XY pairing (see above) and practically all males with X-autosome translocations are infertile due to spermatogenic arrest (54, 78) for which disruption in the formation of the sex vesicle is the obvious cause (53,79). The proper sex vesicle formation is necessary for normal spermatogenesis, and any interference will compromise the process of sperm development (53).…”

Section: X-autosome Translocations In Malesmentioning

confidence: 99%

“…The proper sex vesicle formation is necessary for normal spermatogenesis, and any interference will compromise the process of sperm development (53). In cases of X-autosome translocations, the formation of quadrivalents was proposed, in which the PARs of the Y chromosome associate with the homologous parts of the X chromosome on the derivative X chromosome and the derivative autosome (80).…”

Section: X-autosome Translocations In Malesmentioning

confidence: 99%

“…In contrast, the X and Y chromosomes are not homologous save for the short segments at the end of each chromosome arm, the PARs (39). Both chromosomes differ dramatically in size and gene content and X-Y chromosome homology search and pairing can, therefore, only be mediated by the PARs, conceivably making X-Y segregation particularly difficult (22,28,53).…”

Section: Meiosis and Xy Pairingmentioning

confidence: 99%

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MECHANISMS IN ENDOCRINOLOGY: Aberrations of the X chromosome as cause of male infertility

Röpke

Tüttelmann

2017

European Journal of Endocrinology

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Male infertility is most commonly caused by spermatogenetic failure, clinically noted as oligo-or a-zoospermia. Today, in approximately 20% of azoospermic patients, a causal genetic defect can be identified. The most frequent genetic causes of azoospermia (or severe oligozoospermia) are Klinefelter syndrome (47,XXY), structural chromosomal abnormalities and Y-chromosomal microdeletions. Consistent with Ohno's law, the human X chromosome is the most stable of all the chromosomes, but contrary to Ohno's law, the X chromosome is loaded with regions of acquired, rapidly evolving genes, which are of special interest because they are predominantly expressed in the testis. Therefore, it is not surprising that the X chromosome, considered as the female counterpart of the maleassociated Y chromosome, may actually play an essential role in male infertility and sperm production. This is supported by the recent description of a significantly increased copy number variation (CNV) burden on both sex chromosomes in infertile men and point mutations in X-chromosomal genes responsible for male infertility. Thus, the X chromosome seems to be frequently affected in infertile male patients. Four principal X-chromosomal aberrations have been identified so far: (1) aneuploidy of the X chromosome as found in Klinefelter syndrome (47,XXY or mosaicism for additional X chromosomes). (2) Translocations involving the X chromosome, e.g. nonsyndromic 46,XX testicular disorders of sex development (XX-male syndrome) or X-autosome translocations. (3) CNVs affecting the X chromosome. (4) Point mutations disrupting X-chromosomal genes. All these are reviewed herein and assessed concerning their importance for the clinical routine diagnostic workup of the infertile male as well as their potential to shape research on spermatogenic failure in the next years.

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Sex determination and gender expression: Reproductive investment in snails

Koene

2017

Molecular Reproduction Devel

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SUMMARYSex determination is generally seen as an issue of importance for separate‐sexed organisms; however, when considering other sexual systems, such as hermaphroditism, sex allocation is a less‐binary form of sex determination. As illustrated here, with examples from molluscs, this different vantage point can offer important evolutionary insights. After all, males and females produce only one type of gamete, whereas hermaphrodites produce both. In addition, sperm and accessory gland products are donated bidirectionally. For reciprocal mating, this is obvious since sperm are exchanged within one mating interaction; but even unilaterally mating species end up mating in both sexual roles, albeit not simultaneously. With this in mind, I highlight two factors that play an important role in how reproductive investment is divided in snails: First, the individual's motivation to preferentially donate rather than receive sperm (or vice versa) leads to flexible behavioral performance, and thereby investment, of either sex. Second, due to the presence of both sexual roles within the same individual, partners are potentially able to influence investment in both sexual functions of their partner to their own benefit. The latter has already led to novel insights into how accessory gland products may evolve. Moreover, the current evidence points towards different ways in which allocation to reproduction can be changed in simultaneous hermaphrodites. These often differ from the separate‐sexed situation, highlighting that comparison across different sexual systems may help identify commonalities and differences in physiological, and molecular mechanisms as well as evolutionary patterns. Mol. Reprod. Dev. 84: 132–143, 2017. © 2016 Wiley Periodicals, Inc.

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Function of the Sex Chromosomes in Mammalian Fertility

Cited by 60 publications

References 135 publications

Role and control of X chromosome dosage in mammalian development

Role and control of X chromosome dosage in mammalian development

MECHANISMS IN ENDOCRINOLOGY: Aberrations of the X chromosome as cause of male infertility

Sex determination and gender expression: Reproductive investment in snails

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