A Conserved Hox Axis in the Mouse and Human Female Reproductive System: Late Establishment and Persistent Adult Expression of the Hoxa Cluster Genes
Abstract
The mammalian female reproductive system arises from the uniform paramesonephric duct. The molecular mechanisms that establish differential development along this axis are unknown. We determined the pattern and timing of genes of the Hoxa axis in the development of the Müllerian tract. Hoxa-9, Hoxa-10, Hoxa-11, and Hoxa-13 are all expressed along the length of the paramesonephric duct in the embryonic mouse. After birth, a spatial Hox axis is established, corresponding to the postnatal differentiation of this organ system in the mouse. Hoxa-9 is expressed in the fallopian tubes, Hoxa-10 in the uterus, Hoxa-11 in the uterus and uterine cervix, and Hoxa-13 in the upper vagina. This expression pattern follows the paradigm of spatial colinearity but is a novel exception to temporal colinearity that has been considered typical of Hox genes. These genes remain expressed in the adult mouse and are expressed in the same pattern in the human. The female reproductive system undergoes dramatic structural and functional changes during the estrous cycle and in pregnancy, retaining a high degree of developmental plasticity. The late establishment of a Hox axis and persistent expression of Hox genes in the adult may play an important role in preserving this plasticity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In amniotes, the Hox complex is used to specify axial positions in the urogenital tract.
“in amniotes it is used in the specification of axial positions in the urogeni-tal tract (Kondo et al., 1997;Taylor et al., 1997)”
From Bilaterian Origins: Significance of New Experimental Observations (2000) · cites this paper as Taylor et al., 1997
Cites
Homeobox genes and axial patterning
McGinnis, W., & Krumlauf, R. (1992) · Cell · doi:10.1016/0092-8674(92)90471-n · Cited by 2,674 · see citing works
Hox genes in vertebrate development
Krumlauf, R. K. (1994) · Cell · doi:10.1016/0092-8674(94)90290-9 · Cited by 2,048 · see citing works
Induction of Ectopic Eyes by Targeted Expression of the <i>eyeless</i> Gene in <i>Drosophila</i>
Halder, G., Callaerts, P., & Gehring, W. J. (1995) · Science · doi:10.1126/science.7892602 · Cited by 1,573 · see citing works
Quiring, R., Walldorf, U., Kloter, U., & Gehring, W. J. (1994) · Science · doi:10.1126/science.7914031 · Cited by 1,100 · see citing works
Duboule, D., & Dollé, P. (1989) · The EMBO Journal · doi:10.1002/j.1460-2075.1989.tb03534.x · Cited by 941 · see citing works
Sexually dimorphic sterility phenotypes in HoxalO-deficient mice
Satokata, I., Benson, G., & Maas, R. L. (1995) · Nature · doi:10.1038/374460a0 · Cited by 519 · see citing works
Disruption of the Hoxd-13 gene induces localized heterochrony leading to mice with neotenic limbs
Dollé, P., Dierich, A., LeMeur, M., Schimmang, T., Schuhbaur, B., Chambon, P., & Duboule, D. (1993) · Cell · doi:10.1016/0092-8674(93)90378-4 · Cited by 443 · see citing works
Hoxa 11 structure, extensive antisense transcription, and function in male and female fertility
Hsieh‐Li, H. M., Witte, D. P., Weinstein, M. B., Branford, W., Li, H., Small, K. M., & Potter, S. S. (1995) · Development · doi:10.1242/dev.121.5.1373 · Cited by 392 · see citing works
Izpisúa‐Belmonte, J. C., Falkenstein, H., Dollé, P., Renucci, A., & Duboule, D. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb07764.x · Cited by 341 · see citing works
DNA binding specificity of homeodomains
Laughon, A. S. (1991) · Biochemistry · doi:10.1021/bi00112a001 · Cited by 295 · see citing works
HOX-4 genes and the morphogenesis of mammalian genitalia.Preprint
Dollé, P., Izpisúa‐Belmonte, J. C., Brown, J. M., Tickle, C. A., & Duboule, D. (1991) · Genes & Development · doi:10.1101/gad.5.10.1767 · Cited by 283 · see citing works
Axial homeosis and appendicular skeleton defects in mice with a targeted disruption of hoxd-11
Davis, A. P., & Capecchi, M. R. (1994) · Development · doi:10.1242/dev.120.8.2187 · Cited by 258 · see citing works
Cunha, G. R. (1976) · Journal of Experimental Zoology · doi:10.1002/jez.1401960310 · Cited by 230 · see citing works
Brody, J. R., & Cunha, G. R. (1989) · American Journal of Anatomy · doi:10.1002/aja.1001860102 · Cited by 168 · see citing works
Cervicovaginal epithelium: Its origin and development
Forsberg, J. (1973) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(73)90687-x · Cited by 144 · see citing works
Axial skeleton homeosis and forelimb malformations in Hoxd-11 mutant mice.
Favier, B., LeMeur, M., Chambon, P., & Dollé, P. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.1.310 · Cited by 107 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Leyendecker, G., Bilgicyildirim, A., Inacker, M., Stalf, T., Huppert, P., Mall, G., Böttcher, B., & Wildt, L. (2015) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-014-3437-8 · Cited by 261 · see citing works
Environment, lifestyle, and female infertility
Bala, R., Singh, V., Rajender, S., & Singh, K. (2021) · Reproductive Sciences · doi:10.1007/s43032-020-00279-3 · Cited by 242 · see citing works
Rackow, B. W., & Taylor, H. S. (2010) · Fertility and Sterility · doi:10.1016/j.fertnstert.2008.03.029 · Cited by 239 · see citing works
Self-citationNewbold, R. R., Jefferson, W. N., & Padilla-Banks, E. (2009) · Environmental Health Perspectives · doi:10.1289/ehp.0800045 · Cited by 236 · see citing works
Laganà, A. S., Vitale, S. G., Salmeri, F. M., Triolo, O., Ban Frangež, H., Vrtačnik-Bokal, E., Stojanovska, L., Apostolopoulos, V., Granese, R., & Sofo, V. (2017) · Medical Hypotheses · doi:10.1016/j.mehy.2017.03.032 · Cited by 221 · see citing works
Lee, B., Du, H., & Taylor, H. S. (2009) · Biology of Reproduction · doi:10.1095/biolreprod.108.070391 · Cited by 204 · see citing works
Self-citationRegulatory evolution and the origin of the bilaterians
Peterson, K. J., & Davidson, E. H. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.9.4430 · Cited by 139 · see citing works
MicroRNA 135 regulates HOXA10 expression in endometriosis
Petracco, R., Grechukhina, O., Popkhadze, S., Massasa, E., Zhou, Y., & Taylor, H. S. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1231 · Cited by 138 · see citing works
Self-citationBilaterian Origins: Significance of New Experimental Observations
Peterson, K. J., Cameron, R. A., & Davidson, E. H. (2000) · Developmental Biology · doi:10.1006/dbio.1999.9475 · Cited by 133 · see citing works
HOXA9 promotes ovarian cancer growth by stimulating cancer-associated fibroblasts
Ko, S. Y., Barengo, N., Ladanyi, A., Lee, J.-S., Marini, F., Lengyel, E., & Naora, H. (2012) · Journal of Clinical Investigation · doi:10.1172/jci62229 · Cited by 132 · see citing works
HOXA10 expression is decreased in endometrium of women with adenomyosis
Fischer, C. P., Kayisili, U., & Taylor, H. S. (2011) · Fertility and Sterility · doi:10.1016/j.fertnstert.2010.09.060 · Cited by 133 · see citing works
“In endometriosis, a condition commonly seen with adenomyosis, HOXA10 expression does not increase normally during the midsecretory phase (15).”
Self-citationCakmak, H., & Taylor, H. (2010) · Seminars in Reproductive Medicine · doi:10.1055/s-0029-1242996 · Cited by 105 · see citing works
Self-citationFKBP4 is regulated by HOXA10 during decidualization and in endometriosis
Yang, H., Zhou, Y., Edelshain, B., Schatz, F., Lockwood, C. J., & Taylor, H. S. (2012) · Reproduction · doi:10.1530/rep-11-0438 · Cited by 63 · see citing works
Self-citation
- Authors
- Taylor, H. S., Vanden Heuvel, G. B., & Igarashi, P.
- Affiliations
- Yale University (US)
- Venue
- Biology of Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 1997-12-01
- Volume
- 57
- Issue
- 6
- Pages
- 1338-1345
- ISSN
- 0006-3363 (ISSN-L)
- 1529-7268
- OpenAlex
- W2137050072
- Cited by
- 463
- References
- 16
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 11 · 2023: 13 · 2022: 13 · 2021: 18 · 2020: 18 · 2019: 12 · 2018: 12 · 2017: 12 · 2016: 19 · 2015: 16 · 2014: 27 · 2013: 18 · 2012: 21
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biology of Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- Hox genes, HOXA cluster, female reproductive tract development, paramesonephric duct, Müllerian ducts, HOXA10, oviduct, uterus, uterine cervix, vagina, developmental plasticity, estrous cycle, pregnancy, mice, human
- MeSH terms
- Adult, Aging, Animals, Fallopian Tubes, Female, Genes, Homeobox, Genitalia, Female, Humans, Mesonephros, Mullerian Ducts, Pregnancy, Species Specificity, Uterus, Vagina, Trans-Activators, Gene Expression, In Situ Hybridization, Homeodomain Proteins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
