{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T14:19:46Z","timestamp":1776003586423,"version":"3.50.1"},"reference-count":34,"publisher":"BMJ","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1994,5]]},"abstract":"<jats:p>The susceptibility of females to anencephaly is well established and has been suggested to result from a slower rate of growth and development of female embryos during cranial neurulation. We have tested this hypothesis by measuring the rates of growth and development, both in utero and in vitro, of male and female embryos of the curly tail (ct) mutant mouse strain, in which cranial neural tube defects occur primarily in females. Embryonic growth was assessed by increase in protein content, while development progression was judged from increase in somite number and morphological score. Embryos were sexed by use of the polymerase chain reaction to amplify a DNA sequence specific to the Y chromosome, and by sex chromatin analysis. We find that, during neurulation (between 8.5 and 10.5 days of gestation), males are advanced in growth and development relative to their female litter mates, but that the rates of growth and development do not differ between the sexes during this period. We conclude that rate of embryonic growth and development is unlikely to determine susceptibility to cranial neural tube defects. It seems more likely that male and female embryos differ in some specific aspect(s) of the neurulation process that increases the susceptibility of females to development of anencephaly.<\/jats:p>","DOI":"10.1136\/jmg.31.5.383","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:23:16Z","timestamp":1226330596000},"page":"383-387","source":"Crossref","is-referenced-by-count":37,"title":["Female predisposition to cranial neural tube defects is not because of a difference between the sexes in the rate of embryonic growth or development during neurulation."],"prefix":"10.1136","volume":"31","author":[{"given":"F A","family":"Brook","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J P","family":"Estibeiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A J","family":"Copp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1994,5,1]]},"reference":[{"key":"ref_1","article-title":"Anencephalus: a changing sex ratio. Br 7 Prev Soc Med 1973; 27: 81-4. Female predisposition to cranial neural tube defects","author":"Rogers, S.C.; Morris, M.","unstructured":"Rogers SC, Morris M. Anencephalus: a changing sex ratio. Br 7 Prev Soc Med 1973;27:81-4. Female predisposition to cranial neural tube defects"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/j.1469-8749.1974.tb03442.x","article-title":"Clues to the aetiology of neural tube malformations","volume":"16","author":"Carter, C.O.","year":"1974","unstructured":"Carter CO. Clues to the aetiology of neural tube malformations. Dev Med Child Neurol 1974;16(suppl 32):3-15.","journal-title":"Dev Med Child Neurol"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1002\/ajmg.1320260325","article-title":"Neural tube defects and sex ratios","volume":"26","author":"Seller, M.J.","year":"1987","unstructured":"Seller MJ, Neural tube defects and sex ratios. Am J Med Genet 1987;26:699-707.","journal-title":"Am J Med Genet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1136\/jmg.16.2.129","article-title":"The sex ratio in anencephaly","volume":"16","author":"James, W.H.","year":"1979","unstructured":"James WH. The sex ratio in anencephaly. J Med Genet 1979;16: 129-33.","journal-title":"J Med Genet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1093\/oxfordjournals.aje.a112073","article-title":"Female excess in anencephaly and spina bifida: possible gestational influences","volume":"101","author":"Janerich, D.T.","year":"1975","unstructured":"Janerich DT. Female excess in anencephaly and spina bifida: possible gestational influences. Am J Epidemiol 1975;101:70-6.","journal-title":"Am J Epidemiol"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1136\/jmg.16.3.210","article-title":"spina bifida result from an X- linked defect in a selective abortion mechanism?","volume":"16","author":"Burn, J.; Gibbens, D.","year":"1979","unstructured":"Burn J, Gibbens D. May spina bifida result from an X- linked defect in a selective abortion mechanism? Jf Med Genet 1979;16:210-14.","journal-title":"Jf Med Genet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1136\/jmg.22.4.319-a","article-title":"A possible mechanism underlying the sex selectivity of neural tube defect","volume":"22","author":"James, W.H.","year":"1985","unstructured":"James WH. A possible mechanism underlying the sex selectivity of neural tube defect. J. Med Genet 1985;22:319.","journal-title":"J. Med Genet"},{"key":"ref_8","first-page":"67","article-title":"Anencephaly and spina bifida are usually preventable by avoidance of a specific but unidentified substance present in certain potato tubers","volume":"26","author":"Hypothesis, Renwick J.H.","year":"1972","unstructured":"Renwick JH. Hypothesis. Anencephaly and spina bifida are usually preventable by avoidance of a specific but unidentified substance present in certain potato tubers. Br Jf Prev Soc Med 1972;26:67-88.","journal-title":"Br Jf Prev Soc Med"},{"key":"ref_9","first-page":"19","article-title":"Evidence for an environmental aetiology for anencephalus","volume-title":"Advances in the study of birth defects. Vol 7","author":"Golding, J.","year":"1982","unstructured":"Golding J. Evidence for an environmental aetiology for anencephalus. In: Persaud TVN, ed. Advances in the study of birth defects. Vol 7. New York: Alan R Liss, 1982:19-45."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1530\/jrf.0.0790159","article-title":"Sex difference in mouse embryonic development at neurulation","volume":"79","author":"Seller, M.J.; Perkins-Cole, K.J.","year":"1987","unstructured":"Seller MJ, Perkins-Cole KJ. Sex difference in mouse embryonic development at neurulation. J Reprod Fertil 1987;79:159-61.","journal-title":"J Reprod Fertil"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1136\/bmj.281.6250.1253","article-title":"Ultrasound evidence of sexual difference in fetal size in first trimester","volume":"281","author":"Pedersen, J.F.","year":"1980","unstructured":"Pedersen JF. Ultrasound evidence of sexual difference in fetal size in first trimester. BMJ 1980;281:1253.","journal-title":"BMJ"},{"key":"ref_12","first-page":"52","article-title":"Genetical studies on the skeleton of the mouse. VIII. Curly tail","volume":"52","author":"Gruneberg, H.","year":"1954","unstructured":"Gruneberg H. Genetical studies on the skeleton of the mouse. VIII. Curly tail. _7 Genet 1954;52:52-67."},{"key":"ref_13","first-page":"85","article-title":"Neural tube defects in curly-tail mice. I","volume-title":"Incidence and expression. Proc R Soc Lond B","volume":"206","author":"Embury, S.; Seller, M.J.; Adinolfi, M.; Polani, P.E.","year":"1979","unstructured":"Embury S, Seller MJ, Adinolfi M, Polani PE. Neural tube defects in curly-tail mice. I. Incidence and expression. Proc R Soc Lond B 1979;206:85-94."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1136\/jmg.26.3.160","article-title":"Does lumbosacral spina bifida arise by failure of neural folding or by defective canalisation?","volume":"26","author":"Copp, A.J.; Brook, F.A.","year":"1989","unstructured":"Copp AJ, Brook FA. Does lumbosacral spina bifida arise by failure of neural folding or by defective canalisation?. Med Genet 1989;26:160-6.","journal-title":"Med Genet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/tera.1420240108","article-title":"Quantitation of rat embryonic development in vitro: a morphological scoring system","volume":"24","author":"Brown, N.A.; Fabro, S.","year":"1981","unstructured":"Brown NA, Fabro S. Quantitation of rat embryonic development in vitro: a morphological scoring system. Teratology 1981;24:65-78.","journal-title":"Teratology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry, O.H.; Rosebrough, N.J.; Farr, A.L.; Randall, R.J.","year":"1951","unstructured":"Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. 7 Biol Chem 1951;193:265-75.","journal-title":"7 Biol Chem"},{"key":"ref_17","first-page":"173","article-title":"Extraction of macromolecules from embryonic material","volume-title":"Postimplantation mammalian embryos: a practical approach","author":"Estibeiro, J.P.; Copp, A.J.; Cockroft, D.L.; Brown, N.A.; Clarke, D.O.","year":"1990","unstructured":"Estibeiro JP, Copp AJ, Cockroft DL, Brown NA, Clarke DO. Extraction of macromolecules from embryonic material. In: Copp AJ, Cockroft DL, eds. Postimplantation mammalian embryos: a practical approach. Oxford: IRL Press, 1990:173-204."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1126\/science.2563174","article-title":"Chromosome mapping and expression of a putative testis-determining gene in mouse","volume":"243","author":"Nagamine, C.M.; Chan, K.; Kozak, C.A.; Lau, Y.","year":"1989","unstructured":"Nagamine CM, Chan K, Kozak CA, Lau Y. Chromosome mapping and expression of a putative testis-determining gene in mouse. Science 1989;243:80-3.","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1093\/oso\/9780199630882.003.0016","article-title":"Studying developmental mechanisms in intact embryos","volume-title":"Postimiplantation mammalian embryos: a practical approach","author":"Copp, A.J.","year":"1990","unstructured":"Copp AJ. Studying developmental mechanisms in intact embryos. In: Copp AJ, Cockroft DL, eds. Postimiplantation mammalian embryos: a practical approach. Oxford: IRL Press, 1990:293-316."},{"issue":"8","key":"ref_20","first-page":"1","article-title":"Whole-embryo culture and the study of mammalian embryos during organogenesis","volume":"53","author":"New, D.A.T.","year":"1978","unstructured":"New DAT. Whole-embryo culture and the study of mammalian embryos during organogenesis. Biol Rev 1978;53:8 1-122.","journal-title":"Biol Rev"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/oso\/9780199630882.003.0002","article-title":"Dissection and culture of postimplantation embryos","volume-title":"Postimnplantation mammalian embryos: a practical approach","author":"Cockroft, D.L.","year":"1990","unstructured":"Cockroft DL. Dissection and culture of postimplantation embryos. In: Copp AJ, Cockroft DL, eds. Postimnplantation mammalian embryos: a practical approach. Oxford: IRL Press, 1990:15-40."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3109\/10520297209116541","article-title":"Chromosomes of mouse embryos and newborn young: preparations from membranes and tail tips","volume":"47","author":"Evans, E.P.; Burtenshaw, M.D.; Ford, C.E.","year":"1972","unstructured":"Evans EP, Burtenshaw MD, Ford CE. Chromosomes of mouse embryos and newborn young: preparations from membranes and tail tips. Stain Technol 1972;47:229-34.","journal-title":"Stain Technol"},{"key":"ref_23","article-title":"Statistical methods in biology","author":"Bailey, N.T.","year":"1981","unstructured":"Bailey NT. Statistical methods in biology. London: Edward Arnold, 1981."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/mrd.1120120308","article-title":"Altered sex ratio of live young after transfer of fastand slow-developing mouse embryos","volume":"12","author":"Tsunoda, Y.; Tokunaga, T.; Sugie, T.","year":"1985","unstructured":"Tsunoda Y, Tokunaga T, Sugie T. Altered sex ratio of live young after transfer of fastand slow-developing mouse embryos. Gamete Res 1985;12:301-4.","journal-title":"Gamete Res"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/jez.1402420115","article-title":"Assessment of embryo viability prior to transfer by the non-invasive measurement of glucose uptake","volume":"242","author":"Gardner, D.K.; Leese, H.J.","year":"1987","unstructured":"Gardner DK, Leese HJ. Assessment of embryo viability prior to transfer by the non-invasive measurement of glucose uptake. ] Exp Zool 1987;242:103-5.","journal-title":"Exp Zool"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/0093-691X(91)90306-X","article-title":"Sex and development in bovine in vitro fertilised embryos","volume":"35","author":"Avery, B.; Madison, V.; Greve, R.","year":"1991","unstructured":"Avery B, Madison V, Greve R. Sex and development in bovine in vitro fertilised embryos. Theriogenology 1991;35:953-63.","journal-title":"Theriogenology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1002\/mrd.1080310404","article-title":"Sex-related differences in developmental rates of bovine embryos produced and cultured in vitro","volume":"31","author":"Xu, K.P.; Yadav, B.R.; King, W.A.; Betteridge, K.J.","year":"1992","unstructured":"Xu KP, Yadav BR, King WA, Betteridge KJ. Sex-related differences in developmental rates of bovine embryos produced and cultured in vitro. Mol Reprod Dev 1992;31:249-52.","journal-title":"Mol Reprod Dev"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/274500a0","article-title":"Both X chromosomes function before visible X-chromosome inactivation in female mouse embryos","volume":"274","author":"Epstein, C.J.; Smith, S.; Travis, B.; Tucker, G.","year":"1978","unstructured":"Epstein CJ, Smith S, Travis B, Tucker G. Both X chromosomes function before visible X-chromosome inactivation in female mouse embryos. Nature 1978;274:500-3.","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1242\/dev.118.1.171","article-title":"A paternally imprinted X chromosome retards the development of the early mouse embryo","volume":"118","author":"Thornhill, A.R.; Burgoyne, P.S.","year":"1993","unstructured":"Thornhill AR, Burgoyne PS. A paternally imprinted X chromosome retards the development of the early mouse embryo. Development 1993;118:171-4.","journal-title":"Development"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1242\/dev.117.1.341","article-title":"A Y-chromosomal effect on blastocyst cell number in mice","volume":"117","author":"Burgoyne, P.S.","year":"1993","unstructured":"Burgoyne PS. A Y-chromosomal effect on blastocyst cell number in mice. Development 1993;117:341-5.","journal-title":"Development"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/tera.1420290313","article-title":"Hyperthermia and the induction of neural tube defects in mice","volume":"29","author":"Webster, W.S.; Edwards, M.J.","year":"1984","unstructured":"Webster WS, Edwards MJ. Hyperthermia and the induction of neural tube defects in mice. Teratology 1984;29:417-25.","journal-title":"Teratology"},{"key":"ref_32","first-page":"109","article-title":"Culture of mouse embryos during neurulation. _7 Emlbryol Exp Morphol","volume":"66","author":"Sadler, T.W.; New, D.A.T.","year":"1981","unstructured":"Sadler TW, New DAT. Culture of mouse embryos during neurulation. _7 Emlbryol Exp Morphol 1981;66:109-16."},{"key":"ref_33","first-page":"51","article-title":"Levels of alpha-fetoprotein in amniotic fluids of mice (curly tail) with neural tube defects..7 Med","volume":"13","author":"Adinolfi, M.; Beck, S.E.; Embury, S.; Polani, P.E.; Seller, M.J.","year":"1976","unstructured":"Adinolfi M, Beck SE, Embury S, Polani PE, Seller MJ. Levels of alpha-fetoprotein in amniotic fluids of mice (curly tail) with neural tube defects..7 Med Genet 1976;13:51 1-13.","journal-title":"Genet"},{"key":"ref_34","article-title":"Multifactorial inheritance of neural tube defects: localization of the major gene and recognition of modifiers in ct mutant mice","author":"Neumann, P.E.; Frankel, W.N.; Letts, V.A.; Coffin, J.M.; Copp, A.J.; Bernfield, M.","unstructured":"Neumann PE, Frankel WN, Letts VA, Coffin JM, Copp AJ, Bernfield M. Multifactorial inheritance of neural tube defects: localization of the major gene and recognition of modifiers in ct mutant mice. Nature Genzet (in press).","journal-title":"Nature Genzet"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.31.5.383","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T03:58:19Z","timestamp":1759723099000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.31.5.383"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,5]]},"references-count":34,"journal-issue":{"issue":"5","published-online":{"date-parts":[[1994,5,1]]},"published-print":{"date-parts":[[1994,5]]}},"alternative-id":["10.1136\/jmg.31.5.383"],"URL":"https:\/\/doi.org\/10.1136\/jmg.31.5.383","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,5]]}}}