Endometrial glands are required for preimplantation conceptus elongation and survival

Endometrial glands secrete molecules hypothesized to support conceptus grow th and development. In sheep, endometrial gland morphogenesis occurs postna tally and can be epigenetically ablated by neonatal progestin exposure. The resulting stable adult uterine gland knockout (UGKO) phenotype was used he re to test the hypothesis that endometrial glands are required for successf ul pregnancy. Mature UGKO ewes were bred repeatedly to fertile rams, but no pregnancies were detected by ultrasound on Day 25. Day 7 blastocysts from normal superovulated ewes were then transferred synchronously into Day 7 co ntrol or UGKO ewes. Ultrasonography on Days 25-65 postmating indicated that pregnancy was established in control, but not in UGKO ewes. To examine ear ly uterine-embryo interactions, four control and eight UGKO ewes were bred to fertile rams. On Day 14, their uteri were flushed. The uterus of each co ntrol ewe contained two filamentous conceptuses of normal length. Uteri fro m four UGKO ewes contained no conceptus. Uteri of three UGKO ewes contained a single severely growth-retarded tubular conceptus, whereas the remaining ewe contained a single filamentous conceptus. Histological analyses of the se uteri revealed that endometrial gland density was directly related to co nceptus survival and developmental state. Day 14 UGKO uteri that were devoi d of endometrial glands did not support normal conceptus development and co ntained either no conceptuses or growth-retarded tubular conceptuses. The D ay 14 UGKO uterus with moderate gland development contained a filamentous c onceptus. Collectively, these results demonstrate that endometrial glands a nd, by inference, their secretions are required for periimplantation concep tus survival and development.