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Heart-61

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Protein-12

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Chapter category: Development

Uterine Glands

Chapter authors:
Thomas E. Spencer, Karen D. Carpenter, Kanako Hayashi and Jianbo Hu

This chapter focuses on the comparative development and mechanisms regulating branch ing morphogenesis of endometrial glands in the mammalian uterus. All uteri contain endometrial glands that secrete substances, termed histotroph, essential for conceptus (embryo/fetus and associated extraembryonic membranes) survival, implantation, development and growth. Uterine adenogenesis is the process whereby endometrial glands develop and is primarily a postnatal event in domestic livestock, rodents and humans. Adenogenesis involves initial differentiation and budding of glandular epithelium from luminal epithelium followed by invagination and extensive tubular coiling and branching morphogenesis through the endometrial stroma to the myometrium. The endocrine, cellular and molecular mechanisms regulating uterine adenogenesis are not well defined in any species. In neonatal rodents and pigs, uterine adenogenesis is ovary- and steroid- independent. Estrogen receptor alpha regulates the initial stage of endometrial gland budding and differentiation in the pig, but not rodent or sheep. However, the ovary and uterine estrogen receptor alpha regulate later stages of endometrial gland coiling and branching morphogenesis in sheep. In rodents, pigs and sheep, uterine adenogenesis is a critical period that is sensitive to the detrimental effects of steroid-based endocrine disruptors, which cause functional defects in the adult. In neonatal sheep, pituitary prolactin acts on receptors, expressed exclusively in the nascent and proliferating endometrial glands, to regulate their coiling and branching morphogenetic differentiation. Following postnatal adenogenesis, humans and menstruating primates undergo recurrent endometrial growth and uterine gland branching morphogenesis during the proliferative phase after menstruation. This regrowth is regulated by ovarian estrogen and intrinsic growth factors. In domestic animals, extensive endometrial gland hyperplasia and hypertrophy occur during gestation to provide increasing histotrophic nutrition for fetoplacental growth. In sheep, the sequential actions of ovarian steroid hormones (estrogen and progesterone), the pregnancy recognition signal (interferon tau), and somatolactogenic hormones from the placenta (placental lactogen and growth hormone) constitute a servomechanism that directly regulates endometrial gland morphogenesis and terminal differentiated function. An increased understanding of the mechanisms regulating uterine gland branching morphogenesis is important, because aberrations in this important process can cause infertility, fetal growth retardation, and disease.

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