Molecular mechanisms of development of the human fetal female reproductive tract

Autor: Laurence S. Baskin, Joel Shen, Takeshi Kurita, Gerald R. Cunha, Stanley J. Robboy, Mei Cao
Rok vydání: 2017
Předmět:
0301 basic medicine
Receptors
Steroid
Cancer Research
Squamous Differentiation
Uterus
Reproductive health and childbirth
Epithelium
Cervix
Androgen
Mice
0302 clinical medicine
Receptors
Estrogen receptor
Developmental
Mullerian Ducts
Progesterone
Pediatric
Reproduction
Gene Expression Regulation
Developmental
Cell Differentiation
Genitalia
Female
Müllerian duct
medicine.anatomical_structure
Receptors
Androgen
Vagina
Keratins
Female
Receptors
Progesterone
medicine.medical_specialty
Cell signaling
Mullerian duct
1.1 Normal biological development and functioning
Mesenchyme
Embryonic Development
Biology
Article
Paediatrics and Reproductive Medicine
Andrology
03 medical and health sciences
Uterovaginal canal
Underpinning research
Internal medicine
Progesterone receptor
medicine
Animals
Humans
Genitalia
Urothelium
Steroid
Molecular Biology
Homeodomain Proteins
Contraception/Reproduction
Estrogen Receptor alpha
Cell Biology
Estrogen
Androgen receptor
030104 developmental biology
Endocrinology
Gene Expression Regulation
Biochemistry and Cell Biology
030217 neurology & neurosurgery
Developmental Biology
Zdroj: Cunha, GR; Kurita, T; Caoa, M; Shen, J; Robboy, S; & Baskin, L. (2017). Molecular mechanisms of development of the human fetal female reproductive tract. DIFFERENTIATION, 97, 54-72. doi: 10.1016/j.diff.2017.07.003. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/3h03j6mx
Differentiation; research in biological diversity, vol 97
ISSN: 0301-4681
DOI: 10.1016/j.diff.2017.07.003
Popis: Human female reproductive tract development rests mostly upon hematoxilyn and eosin stained sections despite recent advances on molecular mechanisms in mouse studies. We report application of immunohistochemical methods to explore the ontogeny of epithelial and mesenchymal differentiation markers (keratins, homobox proteins, steroid receptors), transcription factors and signaling molecules (TP63 and RUNX1) during human female reproductive tract development. Keratins 6, 7, 8, 10, 14 and 19 (KRT6, KRT7, KRT8, KRT10, KRT14, KRT19) were expressed in a temporally and spatially dynamic fashion. The undifferentiated Müllerian duct and uterovaginal canal, lined by simple columnar epithelia, expressed KRT7, KRT8 and KRT19. Glandular derivatives of the Müllerian duct (uterine tube, uterine corpus and endocervix) maintained expression of these keratins, while tissues that undergo stratified squamous differentiation (exocervix and vagina) expressed KRT6, KRT14 and KRT10 during development in an age-dependent fashion. TP63 and RUNX1 were expressed prior to KRT14, as these two transcription factors are known to be upstream from KRT14 in developing Müllerian epithelium. In the vagina, KRT10, a marker of terminal differentiation, appeared after endogenous estrogens transformed the epithelium to a thick glycogenated squamous epithelium. Uroplakin, a protein unique to urothelium, was expressed only in the bladder, urethra and vaginal introitus, but not in the female reproductive tract itself. Mesenchymal differentiation was examined through immunostaining for HOXA11 (expressed in uterine mesenchyme) and ISL1 (expressed in vaginal mesenchyme). A detailed ontogeny of estrogen receptor alpha (ESR1), progesterone receptor (PGR) and the androgen receptor (AR) provides the mechanistic underpinning for the teratogenicity of estrogens, progestins and androgens on female reproductive tract development. Immunohistochemical analysis of differentiation markers and signaling molecules advance our understanding of normal development of the human female reproductive tract. These observations demonstrate remarkable similarities in mouse and human female reproductive tract development, but also highlight some key differences.
Databáze: OpenAIRE
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