Molecular and cellular mechanisms for differentiation and regeneration of the uterine endometrium

Tetsuo Maruyama, Yasunori Yoshimura

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

The human endometrium undergoes cyclical changes including proliferation, differentiation, tissue breakdown, and shedding (menstruation) throughout a woman's reproductive life. The postovulatory rise in ovarian progesterone induces profound remodeling and differentiation of the estradiol-primed endometrium. This change, termed decidualization, is crucial for embryo implantation and maintenance of the pregnancy. To date, activation and crosstalk of cAMP- and progesterone-mediated signaling pathways have emerged as key cellular events to drive integrated changes at both the transcriptome and the proteome levels. This results in the induction and maintenance of the decidual phenotype and function. Our recent series of studies highlights the critical role of SRC kinase activation (v-src sarcoma viral oncogene homolog) and STAT5 (signal transducer and activator of transcription 5) phosphorylation in decidualization. After separation of the functional layer of the differentiated endometrium that follows progesterone withdrawal, i.e., menstruation, the basal layer of the endometrium, under the influence of estradiol, regrows and initiates a unique form of angiogenesis and regenerates a new functional layer. The molecular and cellular mechanisms for this process remain elusive, mainly because of difficulties in reproducing menstrual tissue breakdown, shedding, and subsequent tissue regeneration in vitro. We have recently developed a "humanized" mouse model in which a functional human endometrium is reconstituted. It may be used as an in vivo experimental tool for the study of endometrial angiogenesis and regeneration. This model may also be used to identify and test new therapeutic strategies for endometriosis, endometrial cancer, implantation failure, and infertility related to endometrial dysfunction.

Original languageEnglish
Pages (from-to)795-810
Number of pages16
JournalEndocrine Journal
Volume55
Issue number5
DOIs
Publication statusPublished - 2008

Fingerprint

Endometrium
Regeneration
Progesterone
Menstruation
Estradiol
STAT5 Transcription Factor
Pregnancy Maintenance
Endometriosis
Proteome
Endometrial Neoplasms
Oncogenes
Transcriptome
Sarcoma
Infertility
Phosphotransferases
Maintenance
Phosphorylation
Phenotype
Therapeutics

Keywords

  • Animal model
  • Decidualization
  • Endometrium
  • Progesterone
  • Regeneration
  • SRC

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Molecular and cellular mechanisms for differentiation and regeneration of the uterine endometrium. / Maruyama, Tetsuo; Yoshimura, Yasunori.

In: Endocrine Journal, Vol. 55, No. 5, 2008, p. 795-810.

Research output: Contribution to journalArticle

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