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Cite this page: Hill, M.A. (2016) Embryology Vagina Development. Retrieved May 26, 2016, from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Vagina_Development
10 Most Recent Papers
Note - This sub-heading shows an automated computer PubMed search using the listed sub-heading term. References appear in this list based upon the date of the actual page viewing. Therefore the list of references do not reflect any editorial selection of material based on content or relevance. In comparison, references listed on the content page and discussion page (under the publication year sub-headings) do include editorial selection based upon relevance and availability. (More? Pubmed Most Recent)
E Kudela, K Biringer, P Kasajova, M Nachajova, M Adamkov Perivascular epithelioid cell tumors of the uterine cervix. Pathol. Res. Pract.: 2016; PubMed 27083240
Xuyin Zhang, Tiantian Han, Jingxin Ding, Keqin Hua Split thickness skin graft for cervicovaginal reconstruction in congenital atresia of cervix. Fertil. Steril.: 2015, 104(4);e9 PubMed 26211885
Anna Chiarini, Daisong Liu, Ubaldo Armato, Ilaria Dal Prà Bcl10 crucially nucleates the pro-apoptotic complexes comprising PDK1, PKCζ and caspase-3 at the nuclear envelope of etoposide-treated human cervical carcinoma C4-I cells. Int. J. Mol. Med.: 2015; PubMed 26202083
Emily S Miller, Allie Sakowicz, William A Grobman The association between cervical dysplasia, a short cervix, and preterm birth. Am. J. Obstet. Gynecol.: 2015; PubMed 26116102
M Rodríguez-Piñón, C Tasende, D Casuriaga, A Bielli, P Genovese, E G Garófalo Collagen and matrix metalloproteinase-2 and -9 in the ewe cervix during the estrous cycle. Theriogenology: 2015; PubMed 26116057
Ivan Varga, Ladislav Urban, Marianna Kajanová, Štefan Polák Functional histology and possible clinical significance of recently discovered telocytes inside the female reproductive system. Arch. Gynecol. Obstet.: 2016; PubMed 27142517
Tengfei Liu, Xiaoya Chu, Yufei Huang, Ping Yang, Quanfu Li, Lisi Hu, Hong Chen, Qiusheng Chen Androgen-related sperm storage in oviduct of Chinese Soft-Shelled Turtle in vivo during annual cycle. Sci Rep: 2016, 6;20456 PubMed 26847578
Theodoros Petridis, Dimitra Giannakopoulou, Vassiliki Stamatopoulou, Katerina Grafanaki, Christos G Kostopoulos, Helen Papadaki, Christina J Malavaki, Nikos K Karamanos, Stathianna Douroumi, Dionysios Papachristou, George E Magoulas, Dionissios Papaioannou, Denis Drainas Investigation on Toxicity and Teratogenicity in Rats of a Retinoid-Polyamine Conjugate with Potent Anti-Inflammatory Properties. Birth Defects Res. B Dev. Reprod. Toxicol.: 2016; PubMed 26762583
Jesús Ángel Fernández Fernández, Luis Parodi Hueck [Congenital recto-vaginal fistula associated with a normal anus (type H fistula) and rectal atresia in a patient. Report of a case and a brief revision of the literature]. [Asociación de fistula rectovaginal congénita con ano normal (Fístulas Tipo H) y atresia rectal en una paciente. Reporte de un caso y breve revisi6n de la literatura.] Invest Clin: 2015, 56(3);301-7 PubMed 26710545
Quanfu Li, Lisi Hu, Ping Yang, Qian Zhang, Yasir Waqas, Tengfei Liu, Linli Zhang, Shuai Wang, Wei Chen, Yuan Le, Shakeeb Ullah, Qiusheng Chen Expression of TLR2/4 in the sperm-storing oviduct of the Chinese soft-shelled turtle Pelodiscus sinensis during hibernation season. Ecol Evol: 2015, 5(19);4466-4479 PubMed 26664692
The comprehensiveness of the ESHRE/ESGE classification of female genital tract congenital anomalies: a systematic review of cases not classified by the AFS system
Hum Reprod. 2015 May;30(5):1046-1058. Epub 2015 Mar 18.
Di Spiezio Sardo A1, Campo R1, Gordts S1, Spinelli M2, Cosimato C3, Tanos V1, Brucker S1, Li TC1, Gergolet M1, De Angelis C1, Gianaroli L1, Grimbizis G4.
STUDY QUESTION: How comprehensive is the recently published European Society of Human Reproduction and Embryology (ESHRE)/European Society for Gynaecological Endoscopy (ESGE) classification system of female genital anomalies? SUMMARY ANSWER: The ESHRE/ESGE classification provides a comprehensive description and categorization of almost all of the currently known anomalies that could not be classified properly with the American Fertility Society (AFS) system. WHAT IS KNOWN ALREADY: Until now, the more accepted classification system, namely that of the AFS, is associated with serious limitations in effective categorization of female genital anomalies. Many cases published in the literature could not be properly classified using the AFS system, yet a clear and accurate classification is a prerequisite for treatment. STUDY DESIGN, SIZE AND DURATION: The CONUTA (CONgenital UTerine Anomalies) ESHRE/ESGE group conducted a systematic review of the literature to examine if those types of anomalies that could not be properly classified with the AFS system could be effectively classified with the use of the new ESHRE/ESGE system. An electronic literature search through Medline, Embase and Cochrane library was carried out from January 1988 to January 2014. Three participants independently screened, selected articles of potential interest and finally extracted data from all the included studies. Any disagreement was discussed and resolved after consultation with a fourth reviewer and the results were assessed independently and approved by all members of the CONUTA group. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among the 143 articles assessed in detail, 120 were finally selected reporting 140 cases that could not properly fit into a specific class of the AFS system. Those 140 cases were clustered in 39 different types of anomalies. MAIN RESULTS AND THE ROLE OF CHANCE: The congenital anomaly involved a single organ in 12 (30.8%) out of the 39 types of anomalies, while multiple organs and/or segments of Müllerian ducts (complex anomaly) were involved in 27 (69.2%) types. Uterus was the organ most frequently involved (30/39: 76.9%), followed by cervix (26/39: 66.7%) and vagina (23/39: 59%). In all 39 types, the ESHRE/ESGE classification system provided a comprehensive description of each single or complex anomaly. A precise categorization was reached in 38 out of 39 types studied. Only one case of a bizarre uterine anomaly, with no clear embryological defect, could not be categorized and thus was placed in Class 6 (un-classified) of the ESHRE/ESGE system. LIMITATIONS, REASONS FOR CAUTION: The review of the literature was thorough but we cannot rule out the possibility that other defects exist which will also require testing in the new ESHRE/ESGE system. These anomalies, however, must be rare. WIDER IMPLICATIONS OF THE FINDINGS: The comprehensiveness of the ESHRE/ESGE classification adds objective scientific validity to its use. This may, therefore, promote its further dissemination and acceptance, which will have a positive outcome in clinical care and research. STUDY FUNDING/COMPETING INTERESTS: None. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. KEYWORDS: ESHRE/ESGE system; Müllerian anomalies; classification; complex anomaly; comprehensiveness
- three systems have been proposed for the classification of female genital tract anomalies: that of the American Fertility Society (AFS), now the American Society of Reproductive Medicine system (AFS, 1988); the embryological–clinical classification system of genito-urinary malformations (Acién et al., 2004a; Acién and Acién, 2011); and the Vagina, Cervix, Uterus, Adnexa and associated Malformations (VCUAM) system, based on the Tumor, Nodes, Metastases principle in oncology (Oppelt et al., 2005).
Development of epithelial and mesenchymal regionalization of the human fetal utero-vaginal anlagen
J Anat. 2013 Apr;222(4):462-72. doi: 10.1111/joa.12029. Epub 2013 Feb 13.
Fritsch H1, Hoermann R, Bitsche M, Pechriggl E, Reich O.
Literature on the development of the human vagina is abundant; however, contributions concerning the prenatal development of the entire utero-vaginal anlagen (UVA) are rare or carried out in rodents. The primary epithelial characteristics in the adult vagina and uterus are determined during prenatal development and depend on epithelio-mesenchymal stroma interaction; thus an investigation summarizing the spatiotemporal distribution of relevant molecular markers in the entire human UVA will be of current interest. We phenotyped epithelial and mesenchymal characteristics in sagittal sections from 24 female fetuses of 14-34 weeks of gestation and two female newborns by immunostaining with cytokeratins 8, 13, 14 and 17, p63, bcl-2, bmp4, HOX A13, CD31, VEGF, SMA, Pax2 and vimentin. Epithelial differentiation followed a caudal-to-cranial direction in the UVA. Due to the cytokeratin profile of cytokeratins 8, 13 and 14, the characteristics of the different epithelial zones in the UVA could already be recognized in middle-age fetuses. Vaginal epithelium originated from the urogenital sinus in the lower portion and initiated the transformation of vimentin-positive Müllerian epithelium in the upper vaginal portion. During prenatal development the original squamo-columnar junction was clearly detectable from week 24 onwards and was always found in the cervical canal. Early blc-2 positivity within the surrounding mesenchyme of the entire vagina including the portio region pointed to an organ-specific mesenchymal influence. Prenatal findings in human specimens clearly show that fornix epithelium up to the squamo-columnar junction is of vaginal Müllerian origin, and the cervical epithelium cranial to the squamo-columnar junction is of uterine Müllerian origin and includes cells with enough plasticity to transform into squamous epithelium.
© 2013 The Authors Journal of Anatomy © 2013 Anatomical Society.
Normal and abnormal epithelial differentiation in the female reproductive tract
Differentiation. 2011 Oct;82(3):117-26. doi: 10.1016/j.diff.2011.04.008. Epub 2011 May 25.
Kurita T. Source Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. email@example.com
In mammals, the female reproductive tract (FRT) develops from a pair of paramesonephric or Müllerian ducts (MDs), which arise from coelomic epithelial cells of mesodermal origin. During development, the MDs undergo a dynamic morphogenetic transformation from simple tubes consisting of homogeneous epithelium and surrounding mesenchyme into several distinct organs namely the oviduct, uterus, cervix and vagina. Following the formation of anatomically distinctive organs, the uniform MD epithelium (MDE) differentiates into diverse epithelial cell types with unique morphology and functions in each organ. Classic tissue recombination studies, in which the epithelium and mesenchyme isolated from the newborn mouse FRT were recombined, have established that the organ specific epithelial cell fate of MDE is dictated by the underlying mesenchyme. The tissue recombination studies have also demonstrated that there is a narrow developmental window for the epithelial cell fate determination in MD-derived organs. Accordingly, the developmental plasticity of epithelial cells is mostly lost in mature FRT. If the signaling that controls epithelial differentiation is disrupted at the critical developmental stage, the cell fate of MD-derived epithelial tissues will be permanently altered and can result in epithelial lesions in adult life. A disruption of signaling that maintains epithelial cell fate can also cause epithelial lesions in the FRT. In this review, the pathogenesis of cervical/vaginal adenoses and uterine squamous metaplasia is discussed as examples of such incidences. Copyright © 2011. Published by Elsevier B.V.
Vaginal microbiome of reproductive-age women
Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4680-7. Epub 2010 Jun 3.
Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, Karlebach S, Gorle R, Russell J, Tacket CO, Brotman RM, Davis CC, Ault K, Peralta L, Forney LJ.
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA. firstname.lastname@example.org
The means by which vaginal microbiomes help prevent urogenital diseases in women and maintain health are poorly understood. To gain insight into this, the vaginal bacterial communities of 396 asymptomatic North American women who represented four ethnic groups (white, black, Hispanic, and Asian) were sampled and the species composition characterized by pyrosequencing of barcoded 16S rRNA genes. The communities clustered into five groups: four were dominated by Lactobacillus iners, L. crispatus, L. gasseri, or L. jensenii, whereas the fifth had lower proportions of lactic acid bacteria and higher proportions of strictly anaerobic organisms, indicating that a potential key ecological function, the production of lactic acid, seems to be conserved in all communities. The proportions of each community group varied among the four ethnic groups, and these differences were statistically significant [χ(2)(10) = 36.8, P < 0.0001]. Moreover, the vaginal pH of women in different ethnic groups also differed and was higher in Hispanic (pH 5.0 ± 0.59) and black (pH 4.7 ± 1.04) women as compared with Asian (pH 4.4 ± 0.59) and white (pH 4.2 ± 0.3) women. Phylotypes with correlated relative abundances were found in all communities, and these patterns were associated with either high or low Nugent scores, which are used as a factor for the diagnosis of bacterial vaginosis. The inherent differences within and between women in different ethnic groups strongly argues for a more refined definition of the kinds of bacterial communities normally found in healthy women and the need to appreciate differences between individuals so they can be taken into account in risk assessment and disease diagnosis.
Search pubmed: Mullerian ducts
Developmental origin of vaginal epithelium
Differentiation. 2010 Sep-Oct;80(2-3):99-105. doi: 10.1016/j.diff.2010.06.007. Epub 2010 Jul 17.
Abstract The developmental origin of vaginal epithelium has been controversial for nearly a century, with speculation that vaginal epithelium originates from the Müllerian duct, Wolffian duct, and/or urogenital sinus. None of these possibilities have been definitively proven or disproven by direct scientific data. To define precisely the origin of vaginal epithelium, epithelial cells of the Müllerian duct, Wolffian duct, or urogenital sinus were fluorescently labeled in mouse embryos by crossing tdTomato-EGFP dual-reporter transgenic mice with transgenic mouse lines that express Cre-recombinase in each type of epithelium. In embryos and newborn mice, the vagina consisted of fused Müllerian ducts plus the sinus vagina of urogenital sinus origin. However, the proportion of the sinus vagina was significantly reduced as the Müllerian vagina grew caudally. By postpartum day 7, the Müllerian vagina extended to the caudal end of the body, whereas the sinus vagina remained only at the junction between the vagina and perineal skin. As the vagina opened in puberty, urogenital sinus epithelium was detected only in the vulva, but not in the vagina. Additionally, from embryo to adult stages, residual Wolffian duct epithelium was present in the dorsolateral stromal wall of the vagina, but not within vaginal or vulvar epithelium. In conclusion, adult mouse vaginal epithelium is derived solely from Müllerian duct epithelium.
Copyright © 2010 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.
Comment in Derivation of vaginal epithelium finally resolved: broader implications regarding mechanism and pathogenic considerations. [Differentiation. 2010] PMID 20638775
Revisiting old vaginal topics: conversion of the Müllerian vagina and origin of the "sinus" vagina
- "Vaginal development has been a longstanding controversy, which hampers studies on vaginal diseases as well as cervical and uterine diseases. Most concerns center on: why is the vaginal epithelium different from the uterine epithelium; and where does the vagina originate from? It is commonly held that the rodent vagina has a dual origin: the cranial part is derived from the Mullerian duct (Mullerian vagina) and the caudal part derived from the urogenital sinus (sinus vagina). This concept was deduced from morphological observations. However, it cannot explain the difference between the Mullerian vagina and the uterus. Moreover, accumulating new data from genetic and molecular studies contradicts the urogenital sinus origin of the sinus vagina. The present review summarizes previous morphological observations and new findings from genetic and molecular studies, and addresses molecular mechanisms underlying the origin and organogenesis of the vagina in rodents. It provides evidence to show that the whole vagina is derived the Mullerian duct. BMP4 reshapes the intermediate mesoderm-derived Mullerian duct into the vaginal primordium. The latter thus exhibits different features from the uterus, including the stratified squamous epithelium and insensitivity to anti-Mullerian hormone. The sinus vagina is formed by extrinsic BMP4-mediated caudal extension of the Mullerian duct. The present review thus shows how a century of controversy over the origin and organogenesis of the vagina has been resolved. This new understanding will provide additional insight into genetic diseases and tumors of the female reproductive tract."
Fetal development of the female external urinary sphincter complex: an anatomical and histological study
Sebe P, Fritsch H, Oswald J, Schwentner C, Lunacek A, Bartsch G, Radmayr C. J Urol. 2005 May;173(5):1738-42; discussion 1742. PMID: 15821572
Experimental contributions to the study of the embryology of the vagina
Sánchez-Ferrer ML, Acién MI, Sánchez del Campo F, Mayol-Belda MJ, Acién P. Hum Reprod. 2006 Jun;21(6):1623-8. Epub 2006 Feb 13.
BACKGROUND: Acién's hypothesis, deduced from patients with malformations of the female genital tract, especially those with renal agenesis and ipsilateral blind hemivagina, affirms the embryology of the human vagina as deriving from the Wolffian ducts and the Müllerian tubercle and could explain the embryological origin of all the female genital malformations reported. In this study, we investigated the hypothesis in rats.
METHODS: Twenty-five pregnant rats were used to analyse female embryos (64) from day 15 (stage indifferent) to day 20 postcoitum (vagina completely formed). We performed transverse and longitudinal sections of embryos, haematoxylin-eosin tinction and immunohistochemical staining using markers specific to Wolffian derivatives. We also analysed the presence of these markers in the vagina of four adult rats.
RESULTS: The Müller ducts converge until they fuse into one tube, but caudally they diverge and finally they fuse with the 'urogenital sinus bulbs' that are actually the distal portion of the Wolffian ducts according to the immunohistochemical marking with GZ1 and GZ2. The Müllerian tubercle is observed between those elements. Then, the immunohistochemical staining can be seen all along the completely formed vagina, which is also observed in the vagina of the adult rat.
CONCLUSION: We prove the participation of Müller tubercle and Wolffian ducts in the formation of the vagina in rats, so we confirm experimentally Acién's hypothesis about the human vagina embryology.
PMID: 16476676 http://www.ncbi.nlm.nih.gov/pubmed/16476676
Lifetime changes in the vulva and vagina
Farage M, Maibach H. Arch Gynecol Obstet. 2006 Jan;273(4):195-202. Epub 2005 Oct 6. Review. PMID: 16208476
- "The morphology and physiology of the vulva and vagina change over a lifetime. The most salient changes are linked to puberty, the menstrual cycle, pregnancy, and menopause. The cutaneous epithelia of the mons pubis, labia, and clitoris originate from the embryonic ectoderm and exhibit a keratinized, stratified structure similar to the skin at other sites. The mucosa of the vulvar vestibule, which originates from the embryonic endoderm, is non-keratinized. The vagina, derived from the embryonic mesoderm, is responsive to estrogen cycling. At birth, the vulva and vagina exhibit the effects of residual maternal estrogens. During puberty, the vulva and vagina acquire mature characteristics in a sequential fashion in response to adrenal and gonadal maturation. A trend to earlier pubertal onset has been observed in Western developed countries. In women of reproductive age, the vaginal mucosa responds to steroid hormone cycling, exhibiting maximal thickness and intracellular glycogen content at mid-cycle. Vulvar skin thickness remains unchanged but menstrual cycle-associated changes in ortho- and parakeratosis occur at the cytological level. The vulva and vagina further adapt to the needs of pregnancy and delivery. After menopause, tissue atrophy ensues. Post-menopausal changes in skin barrier function, skin hydration, and irritant susceptibility have been observed on exposed skin but not on the vulva. Nevertheless, older women with incontinence are at increased risk for developing incontinence dermatitis. A combination of factors, such as tissue atrophy, slower dissipation of excess skin hydration, shear forces associated with limited mobility, and lower tissue regeneration capacity increase the risk of morbidity from incontinence dermatitis in older women."
Baseline dimensions of the human vagina
Barnhart KT, Izquierdo A, Pretorius ES, Shera DM, Shabbout M, Shaunik A. Hum Reprod. 2006 Jun;21(6):1618-22. Epub 2006 Feb 14. PMID: 16478763
- magnetic resonance imaging (MRI) to quantify distribution of a vaginal gel. Seventy-seven MRI scans were performed on 28 women before gel application to establish baseline vaginal measurements. Average dimensions were calculated for each woman and for the population. The influence of potential covariates (age, height, weight and parity) on these dimensions was assessed. ...Mean vaginal length from cervix to introitus was 62.7 mm. Vaginal width was largest in the proximal vagina (32.5 mm), decreased as it passed through the pelvic diaphragm (27.8 mm) and smallest at the introitus (26.2 mm)."
New concepts on the development of the vagina
Shapiro E, Huang H, Wu XR. Adv Exp Med Biol. 2004;545:173-85. Review. No abstract available. PMID: 15086027
Fetal development of the female external urinary sphincter complex: an anatomical and histological study
Sebe P, Fritsch H, Oswald J, Schwentner C, Lunacek A, Bartsch G, Radmayr C. J Urol. 2005 May;173(5):1738-42; discussion 1742. PMID: 15821572
- Helper function of the Wolffian ducts and role of androgens in the development of the vagina. Drews U. Sex Dev. 2007;1(2):100-10. PMID: 18391520
- "Here experiments with the complete androgen receptor defect in the testicular feminisation (Tfm) mouse are reported which show that the vagina is formed by caudal migration of Wolffian and Müllerian ducts. The cranial ends of the Wolffian ducts successively regress while the Müllerian ducts fuse to form the vagina. Immunohistochemistry of the androgen receptor reveals that the caudal ends of the Wolffian ducts remain in the indifferent stage and therefore have been mistaken as sinuvaginal bulbs. The Wolffian ducts do not contribute to the vagina itself but have a helper function during downward movement of the vaginal bud in the female. In the male the caudal ends serve as androgen operated switch for the negative control of vaginal development. The results indicate that the rudimentary vagina in the complete androgen insensitivity syndrome (CAIS) corresponds to non obliterated caudal ends of the Müllerian ducts. Selective atresia of the vagina in the MRKH (Mayer-Rokitansky-Kuster-Hauser) syndrome may be explained by the failure of Wolffian and Müllerian ducts to descend caudally"
Preliminary Note on the Development of the Clitoris, Vagina, and Hymen
J Anat Physiol. 1896 Oct;31(Pt 1):18-28.11.
PMID: 17232227 http://www.ncbi.nlm.nih.gov/pubmed/17232227
PMCID: PMC1327808 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1327808
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome
text and table below from http://www.ojrd.com/content/2/1/13
Surgical creation of a neovagina A number of techniques are appropriate for the correction of vaginal agenesis and there is no consensus regarding the best option, the approach being most often based on the surgeon's experience. Three methods are currently in use:
- The Abbe-McIndoe operation: this involves the dissection of a space between the rectum and the bladder, placement of a mold covered with a skin graft into the space, and diligent postoperative vaginal dilatation. Modifications of this procedure rely on spontaneous epithelialization or on the use of different materials such as peritoneum , minora labia grafting, or synthetic materials [112,113].
- The Vecchietti operation is a mixture of surgical and nonsurgical methods. It has been performed frequently in Europe over the last 20 years . This procedure involves the creation of a neovagina via dilatation with a traction device attached to the abdomen, sutures placed subperitoneally by laparotomy, and a plastic olive placed in the vaginal dimple. A laparoscopic or celioscopic modification is often preferred and leads to comparable results .
- Sigmoidal colpoplasty: this technique involves vaginal replacement or creation of a neovagina by grafting a 12–18 cm long segment of sigmoid , providing that a single and/or left pelvic kidney does not impair the procedure. Sigmoidal colpoplasty is believed to be an efficient procedure giving excellent results, although complete adequacy for coital function often requires prolonged care and support .
|Summary of differential diagnosis between MRKH syndrome and isolated vaginal atresia, WNT4 syndrome, and androgen insensitivity syndrome.|
|Morcel et al. Orphanet Journal of Rare Diseases 2007 2:13 doi:10.1186/1750-1172-2-13|
Complex malformations of the female genital tract. New types and revision of classification. Acién P, Acién M, Sánchez-Ferrer M. Hum Reprod. 2004 Oct;19(10):2377-84. Epub 2004 Aug 27. PMID: 15333604
The development of the human vagina
BULMER D. J Anat. 1957 Oct;91(4):490-509.No abstract available. PMID: 13475148 | PMCID: 1244904
- Yi Cai Revisiting old vaginal topics: conversion of the Müllerian vagina and origin of the "sinus" vagina. Int. J. Dev. Biol.: 2009, 53(7);925-34 PubMed 19598112