Because of its function, the X chromosome has a special status in mammalian genomes, with the specific occurrence of genes that influence both female and male fertility. Long ago, the XO karyotype (Turner syndrome) was associated with infertility, proving the correlation between normal X chromosome dosage and normal female fertility. Nevertheless, the search for specific X-borne fertility genes was not completely successful and suggested, instead, that female X-linked fertility, for example, depends upon groups of X-linked genes. Conversely, X-linked hyperfertility has been observed in sheep, where a mutation in BMP15 leads to a hyperfertile phenotype, but only in the heterozygous state. Many male fertility genes map to the X chromosome, consistent with a genetic model developed in the early 1990s. Ironically, NR0B1 (formerly DAX1), once presented as the paradigm of genes responsible for ovarian development and function, is probably one of these male fertility factors and is active in the maintenance of spermatogenesis. Indeed, duplications of this gene on the human X chromosome lead to XY sex reversal, as NR0B1 is able to counterbalance the effect in humans. Nevertheless, invalidation experiments in mice demonstrate the effect of this factor on male germ-cell production.    

Bardoni B, Zanaria E, Guioli S, Floridia G, Worley KC, Tonini G, Ferrante E, Chiumello G, McCabe ER, Fraccaro M, et al.: A dosage sensitive locus at chromosome Xp21 is involved in male to female sex reversal. Nature Genet 7:497–501 (1994).
Bione S, Sala C, Manzini C, Arrigo G, Zuffardi O, Banfi S, Borsani G, Jonveaux P, Philippe C, Zuccotti M, Ballabio A, Toniolo D: A human homologue of the Drosophila melanogaster diaphanous gene is disrupted in a patient with premature ovarian failure: evidence for conserved function in oogenesis and implications for human sterility. Am J hum Genet 62:533–541 (1998).
Bodensteiner KJ, McNatty KP, Clay CM, Moeller CL, Sawyer HR: Expression of growth and differentiation factor-9 in the ovaries of fetal sheep homozygous or heterozygous for the Inverdale prolificacy gene (FecX(I)). Biol Reprod 62:1479–1485 (2000).
Bradford GE, Quirke JF, Sitorus P, Inounu I, Tiesnamurti B, Bell FL, Fletcher IC, Torell DT: Reproduction in Javanese sheep: evidence for a gene with large effect on ovulation rate and litter size. J anim Sci 63:418–431 (1986).
Branford WW, Zhao GQ, Valerius MT, Weinstein M, Birkenmeier EH, Rowe LB, Potter SS: Spx1, a novel X-linked homeobox gene expressed during spermatogenesis. Mech Dev 65:87–98 (1997).
Burgoyne PS, Mc Laren A: Does X-Y pairing during male meiosis protect the paired region on the X chromosome from subsequent X-inactivation? Hum Genet 70:82–83 (1985).
Clarkson MJ, Harley VR: Sex with two SOX on: SRY and SOX9 in testis development. Trends Endocrinol Metab 13:106–111 (2002).
Crisponi L, Deiana M, Loi A, Chiappe F, Uda M, Amati P, Bisceglia L, Zelante L, Nagaraja R, Porcu S, Ristaldi MS, Marzella R, Rocchi M, Nicolino M, Lienhardt-Roussie A, Nivelon A, Verloes A, Schlessinger D, Gasparini P, Bonneau D, Cao A, Pilia G: The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome. Nature Genet 27:159–166 (2001).
Dale L, Jones CM: BMP signalling in early Xenopus development. BioEssays 21:751–760 (1999).
Davis GH, Dodds KG, Wheeler R, Jay NP: Evidence that an imprinted gene on the X chromosome increases ovulation rate in sheep. Biol Reprod 64:216–221 (2001).
Davis GH, McEwan JC, Fennessy PF, Dodds KG, Farquhar PA: Evidence for the presence of a major gene influencing ovulation rate on the X chromosome of sheep. Biol Reprod 44:620–624 (1991).
Davison RM, Fox M, Conway GS: Mapping of the POF1 locus and identification of putative genes for premature ovarian failure. Mol hum Reprod 6:314–318 (2000).
Davison RM, Quilter CR, Webb J, Murray A, Fisher AM, Valentine A, Serhal P, Conway GS: A familial case of X chromosome deletion ascertained by cytogenetic screening of women with premature ovarian failure. Hum Reprod 13:3039–3041 (1998).
Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM: Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 383:531–535 (1996).
Galloway SM, McNatty KP, Cambridge LM, Laitinen MP, Juengel JL, Jokiranta TS, McLaren RJ, Luiro K, Dodds KG, Montgomery GW, Beattie AE, Davis GH, Ritvos O: Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nature Genet 25:279–283 (2000).
Hickey T, Chandy A, Norman RJ: The androgen receptor CAG repeat polymorphism and X-chromosome inactivation in Australian Caucasian women with infertility related to polycystic ovary syndrome. J clin Endocrinol Metab 87:161–165 (2002).
Kerr SM, Taggart MH, Lee M, Cooke HJ: Ott, a mouse X-linked multigene family expressed specifically during meiosis. Hum molec Genet 5:1139–1148 (1996).
Koopman P: Sry and Sox9: mammalian testis-determining genes. Cell molec Life Sci 55:839–856 (1999).
Krauss CM, Turksoy RN, Atkins L, McLaughlin C, Brown LG, Page DC: Familial premature ovarian failure due to an interstitial deletion of the long arm of the X chromosome. N Engl J Med 317:125–131 (1987).
Mach JM, Lehmann R: An Egalitarian-BicaudalD complex is essential for oocyte specification and axis determination in Drosophila. Genes Dev 11:423–435 (1997).
McElreavey K, Vilain E, Abbas N, Herskowitz I, Fellous M: A regulatory cascade hypothesis for mammalian sex determination: SRY represses a negative regulator of male development. Proc natl Acad Sci, USA 90:3368–3372 (1993).
Montgomery GW, Crawford AM, Penty JM, Dodds KG, Ede AJ, Henry HM, Pierson CA, Lord EA, Galloway SM, Schmack AE, et al.: The ovine Booroola fecundity gene (FecB) is linked to markers from a region of human chromosome 4q [see comments]. Nature Genet 4:410–414 (1993).
Mulsant P, Lecerf F, Fabre S, Schibler L, Monget P, Lanneluc I, Pisselet C, Riquet J, Monniaux D, Callebaut I, Cribiu E, Thimonier J, Teyssier J, Bodin L, Cognie Y, Chitour N, Elsen JM: Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Merino ewes. Proc natl Acad Sci, USA 98:5104–5109 (2001).
Mumm S, Herrera L, Waeltz PW, Scardovi A, Nagaraja R, Esposito T, Schlessinger D, Rocchi M, Forabosco A: X/autosomal translocations in the Xq critical region associated with premature ovarian failure fall within and outside genes. Genomics 76:30–36 (2001).
Ohno S: Sex Chromosomes and Sex-Linked Genes (Springer-Verlag, Berlin 1967).
Pailhoux E, Vigier B, Chaffaux S, Servel N, Taourit S, Furet JP, Fellous M, Grosclaude F, Cribiu EP, Cotinot C, Vaiman D: A 11.7-kb deletion triggers intersexuality and polledness in goats. Nature Genet 29:453–458 (2001).
Piumi F, Schibler L, Vaiman D, Oustry A, Cribiu EP: Comparative cytogenetic mapping reveals chromosome rearrangements between the X chromosomes of two closely related mammalian species (cattle and goats). Cytogenet Cell Genet 81:36–41 (1998).
Powell CM, Taggart RT, Drumheller TC, Wangsa D, Qian C, Nelson LM, White BJ: Molecular and cytogenetic studies of an X;autosome translocation in a patient with premature ovarian failure and review of the literature. Am J med Genet 52:19–26 (1994).
Prueitt RL, Ross JL, Zinn AR: Physical mapping of nine Xq translocation breakpoints and identification of XPNPEP2 as a premature ovarian failure candidate gene. Cytogenet Cell Genet 89:44–50 (2000).
Rao E, Weiss B, Fukami M, Rump A, Niesler B, Mertz A, Muroya K, Binder G, Kirsch S, Winkelmann M, Nordsiek G, Heinrich U, Breuning MH, Ranke MB, Rosenthal A, Ogata T, Rappold GA: Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome. Nature Genet 16:54–63 (1997).
Rice WR: Sexually antagonistic genes: experimental evidence. Science 256:1436–1439 (1992).
Swain A, Narvaez V, Burgoyne P, Camerino G, Lovell-Badge R: Dax1 antagonizes Sry action in mammalian sex determination. Nature 391:761–767 (1998).
Tharapel AT, Anderson KP, Simpson JL, Martens PR, Wilroy Jr RS, Llerena Jr JC, Schwartz CE: Deletion (X)(q26.1→q28) in a proband and her mother: molecular characterization and phenotypic- karyotypic deductions. Am J hum Genet 52:463–471 (1993).
Vaiman D, Pailhoux E: Mammalian intersexes: deciphering the sex determination cascade. Trends Genet 16:488–494 (2000).
Vainio S, Heikkila M, Kispert A, Chin N, McMahon AP: Female development in mammals is regulated by Wnt-4 signalling. Nature 397:405–409 (1999).
Wang PJ, McCarrey JR, Yang F, Page DC: An abundance of X-linked genes expressed in spermatogonia. Nature Genet 27:422–426 (2001).
Yu RN, Ito M, Saunders TL, Camper SA, Jameson JL: Role of Ahch in gonadal development and gametogenesis. Nature Genet 20:353–357 (1998).
Zanaria E, Muscatelli F, Bardoni B, Strom TM, Guioli S, Guo W, Lalli E, Moser C, Walker AP, McCabe ER, et al.: An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita. Nature 372:635–641 (1994).
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.