Analysis of obstetric complications and uterine connective tissue in tenascin-X-deficient humans and mice
Open accessAbstract
Tenascin-X (TNX) is a large, multi-domain, extracellular matrix glycoprotein. Complete deficiency of TNX in humans leads to a recessive form of Ehlers-Danlos syndrome (EDS), and TNX haploinsufficiency is a cause of hypermobility type EDS. EDS patients appear to have a higher risk of several complications during pregnancy, such as pelvic instability, premature rupture of membranes, and postpartum hemorrhage. Here, we present a study of genitourinary and obstetric complications in TNX-deficient women of reproductive age. We have found complications, such as uterus prolapses, that are in agreement with previous findings in other EDS types. In TNX knockout (KO) mice, we have observed mild pregnancy-related abnormalities. Morphological and immunohistological analysis of uterine tissues has not revealed obvious quantitative or spatial differences between TNX KO and wildtype mice with respect to collagen types I, III, V, and XII or elastic fibers. We conclude that TNX-deficient women are at risk of obstetric complications, but that TNX KO mice show only a mild phenotype. Furthermore, we show that TNX is involved in the stability of elastic fibers rather than in their initial deposition.
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Demirdas et al. described the gynecologic and obstetric history of seven women in their cohort; four women not previously included reported a total of 10 pregnancies, two of which ended in intrauterine demise.
“Demirdas et al. [2016] described the gynecologic and obstetric history of seven women in their cohort.Three of these women had previously been included in the study by Egging et al. [2008].The other four women reported a total of 10 pregnancies, two of which ended in intrauterine demise of the fetus.”
From The Ehlers–Danlos syndromes, rare types (2017) · cites this paper as Egging et al. [2008]
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Experimental — accuracy not yet measuredUterine and vaginal prolapse regularly occurs in TNX-deficient women, even at a young age, suggesting laxity of the genitourinary tissues.
“However, uterine and vaginal prolapse regularly occurs in TNX-deficient women, even at a young age, suggesting laxity of the genitourinary tissues.”
From The Ehlers–Danlos syndromes, rare types (2017) · cites this paper as Egging et al. [2008]
Pregnancy is without major complications in TNX-deficient patients, apart from one incident of postpartum hemorrhage.
“The authors concluded that pregnancy is without major complications in TNX-deficient patients, apart from one incident of postpartum hemorrhage.”
From The Ehlers–Danlos syndromes, rare types (2017) · cites this paper as Egging et al. [2008]
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Cites
A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency
Schalkwijk, J., Zweers, M. C., Steijlen, P. M., Dean, W. B., Taylor, G., van Vlijmen, I. M., van Haren, B., Miller, W. L., & Bristow, J. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa002939 · Cited by 391 · see citing works
Self-citationTenascin-X deficiency is associated with Ehlers-Danlos syndrome
Burch, G. H., Gong, Y., Liu, W., Dettman, R. W., Curry, C. J., Smith, L., Miller, W. L., & Bristow, J. (1997) · Nature Genetics · doi:10.1038/ng0997-104 · Cited by 366 · see citing works
Mao, J. R., Taylor, G., Dean, W. B., Wagner, D. R., Afzal, V., Lotz, J. C., Rubin, E. M., & Bristow, J. (2002) · Nature Genetics · doi:10.1038/ng850 · Cited by 261 · cited 3× · see citing works
“Bars 50 μm et al. 1997; Egging et al. 2006b; Lindor and Bristow 2005; Mao et al. 2002; Matsumoto et al. 2001; Minamitani et al. 2004; Schalkwijk et al. 2001; Zweers et al. 2004).”
BackgroundMethodHaploinsufficiency of TNXB Is Associated with Hypermobility Type of Ehlers-Danlos Syndrome
Zweers, M. C., Bristow, J., Steijlen, P. M., Dean, W. B., Hamel, B. C., Otero, M., Kucharekova, M., Boezeman, J. B., & Schalkwijk, J. (2003) · The American Journal of Human Genetics · doi:10.1086/376564 · Cited by 242 · see citing works
Self-citationTumour invasion and metastasis are promoted in mice deficient in tenascin‐X
Matsumoto, K., Takayama, N., Ohnishi, J., Ohnishi, E., Shirayoshi, Y., Nakatsuji, N., & Ariga, H. (2001) · Genes to Cells · doi:10.1046/j.1365-2443.2001.00482.x · Cited by 81 · see citing works
Characterization of the bovine Tenascin-X
Elefteriou, F., Exposito, J.-Y., Garrone, R., & Lethias, C. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.36.22866 · Cited by 47 · see citing works
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The Ehlers–Danlos syndromes, rare types
Brady, A. F., Demirdas, S., Fournel‐Gigleux, S., Ghali, N., Giunta, C., Kapferer‐Seebacher, I., Kosho, T., Mendoza‐Londono, R., Pope, M. F., Rohrbach, M., et al. (2017) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31550 · Cited by 249 · see citing works
Merke, D. P., Chen, W., Morissette, R., Xu, Z., Van Ryzin, C., Sachdev, V., Hannoush, H., Shanbhag, S. M., Acevedo, A. T., Nishitani, M., et al. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-3148 · Cited by 82 · see citing works
- Authors
- Egging, D. F., van Vlijmen-Willems, I., Choi, J., Peeters, A. C. T. M., van Rens, D., Veit, G., Koch, M., Davis, E. C., & Schalkwijk, J.
- Affiliations
- Radboud University Medical Center (NL)
- University of Cologne (DE)
- McGill University (CA)
- Corresponding author
- Schalkwijk, Joost
- Venue
- Cell and Tissue Research
- Published
- 2008-03-12
- Volume
- 332
- Issue
- 3
- Pages
- 523-532
- ISSN
- 0302-766X (ISSN-L)
- 1432-0878
- PMC
- PMC2386751
- OpenAlex
- W2075531286
- Cited by
- 27
- References
- 6
- Citations by year
- 2025: 1 · 2023: 1 · 2021: 4 · 2020: 2 · 2019: 1 · 2017: 2 · 2016: 3 · 2013: 2 · 2012: 2
- FWCI
- 1.71
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Cell and Tissue Research (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- Radboud Universiteit
- Canadian Institutes of Health Research
- Lawrence Berkeley National Laboratory
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy-related medical research
- Health Sciences › Medicine › Rheumatology › Pelvic floor disorders treatments
- Keywords
- tenascin-X, Ehlers-Danlos syndrome, pregnancy complications, uterine prolapse, elastic fibers, collagen, knockout mice, pregnancy, premature rupture of membranes, postpartum hemorrhage, pelvic instability, genitourinary complications, extracellular matrix
- MeSH terms
- Adult, Animals, Ehlers-Danlos Syndrome, Elastic Tissue, Female, Humans, Middle Aged, Pregnancy, Pregnancy Complications, Uterus, Mice, Knockout, Tenascin, Fibrillar Collagens, Mice, Female Urogenital Diseases
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