Sheep Uterine Gland Knockout (UGKO) Model

Abstract

Endometrial gland development is a postnatal event in the ovine uterus that can be inhibited epigenetically by chronic exposure of ewe lambs to a synthetic progestin after birth. The uterus of neonatally progestinized ewes lack endometrial glands and display a uterine gland knockout (UGKO) phenotype. Progestin ablation of endometrial gland development is specific, because it does not affect development of extra-uterine reproductive tract structures or the hypothalamic-pituitary-ovarian axis. The UGKO ewe is a useful model for study of uterine development and the role of endometrial glands in uterine function during the estrous cycle and pregnancy. UGKO ewes exhibit altered estrous cycles due to the inability of the uterus to produce luteolytic pulses of prostaglandin F2alpha. UGKO ewes are infertile, and blastocysts hatch normally but fail to survive or elongate during early pregnancy. This pregnancy defect is primarily due to the absence of endometrial glands and their secretions rather than alterations in expression of either anti-adhesive or adhesive molecules on the endometrial epithelium. Genomics and proteomics are being used to identify specific components of histotroph that are absent or diminished in the UGKO ewe and will serve as markers of endometrial function and uterine receptivity.