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a Center for Animal Biotechnology and Genomics, Department of Animal Science, Texas A&M University, College Station, Texas 77843
b Department of Animal and Dairy Sciences, Program in Cell and Molecular Biosciences, Auburn University, Auburn, Alabama 36849
All mammalian uteri contain endometrial glands that synthesize or transport and secrete substances essential for survival and development of the conceptus (embryo/fetus and associated extraembryonic membranes). In rodents, uterine secretory products of the endometrial glands are unequivocally required for establishment of uterine receptivity and conceptus implantation. Analyses of the ovine uterine gland knockout model support a primary role for endometrial glands and, by default, their secretions in peri-implantation conceptus survival and development. Uterine adenogenesis is the process whereby endometrial glands develop. In humans, this process begins in the fetus, continues postnatally, and is completed during puberty. In contrast, endometrial adenogenesis is primarily a postnatal event in sheep, pigs, and rodents. Typically, endometrial adenogenesis involves differentiation and budding of glandular epithelium from luminal epithelium, followed by invagination and extensive tubular coiling and branching morphogenesis throughout the uterine stroma to the myometrium. This process requires site-specific alterations in cell proliferation and extracellular matrix (ECM) remodeling as well as paracrine cell-cell and cell-ECM interactions that support the actions of specific hormones and growth factors. Studies of uterine development in neonatal ungulates implicate prolactin, estradiol-17ß, and their receptors in mechanisms regulating endometrial adenogenesis. These same hormones appear to regulate endometrial gland morphogenesis in menstruating primates and humans during reconstruction of the functionalis from the basalis endometrium after menses. In sheep and pigs, extensive endometrial gland hyperplasia and hypertrophy occur during gestation, presumably to provide increasing histotrophic support for conceptus growth and development. In the rabbit, sheep, and pig, a servomechanism is proposed to regulate endometrial gland development and differentiated function during pregnancy that involves sequential actions of ovarian steroid hormones, pregnancy recognition signals, and lactogenic hormones from the pituitary or placenta. That disruption of uterine development during critical organizational periods can alter the functional capacity and embryotrophic potential of the adult uterus reinforces the importance of understanding the developmental biology of uterine glands. Unexplained high rates of peri-implantation embryonic loss in humans and livestock may reflect defects in endometrial gland morphogenesis due to genetic errors, epigenetic influences of endocrine disruptors, and pathological lesions.
1 Supported in part by NIH grant R01-HD38274 to T.E.S., NRI Competitive Grants Program/USDA grant 98-35203-6322 to T.E.S. and grant 95-37203-1995 to F.F.B., and NIH grant P30 ES09106.
2 Correspondence: Thomas E. Spencer, Center for Animal Biotechnology and Genomics, 442 Kleberg Center, 2471 TAMU, Texas A&M University, College Station, TX 77843-2471. FAX: 979 862 2662; tspencer{at}ansc.tamu.edu
3 Current address: Department of Animal and Veterinary Science, Center for Reproductive Biology, University of Idaho, Moscow, ID 83844-2330.
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B. J. Tarleton, T. D. Braden, A. A. Wiley, and F. F. Bartol Estrogen-Induced Disruption of Neonatal Porcine Uterine Development Alters Adult Uterine Function Biol Reprod, April 1, 2003; 68(4): 1387 - 1393. [Abstract] [Full Text] [PDF]
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S. Noel, A. Herman, G. A. Johnson, C. A. Gray, M. D. Stewart, F. W. Bazer, A. Gertler, and T. E. Spencer Ovine Placental Lactogen Specifically Binds to Endometrial Glands of the Ovine Uterus Biol Reprod, March 1, 2003; 68(3): 772 - 780. [Abstract] [Full Text] [PDF]
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K. D. Carpenter, C. A. Gray, S. Noel, A. Gertler, F. W. Bazer, and T. E. Spencer Prolactin Regulation of Neonatal Ovine Uterine Gland Morphogenesis Endocrinology, January 1, 2003; 144(1): 110 - 120. [Abstract] [Full Text] [PDF]
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Q. Li, H. Wang, Y. Zhao, H. Lin, Q. A. Sang, and C. Zhu Identification and specific expression of matrix metalloproteinase-26 in rhesus monkey endometrium during early pregnancy Mol. Hum. Reprod., October 1, 2002; 8(10): 934 - 940. [Abstract] [Full Text] [PDF]
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