Proteins released by cultured Day 15-16 conceptuses prolong luteal maintenance when introduced into the uterine lumen of cyclic ewes

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Abstract
Experiments were performed to determine whether proteins, produced and released into the incubation medium by day 15-16 sheep conceptuses cultured for 24-48 h, could prolong the functional lifespan of the corpus luteum (CL) when infused into the uterine lumen of cyclic ewes. Beginning on day 12 (estrus = day 0) either a concentrated (2 ml) solution of total conceptus culture medium protein (2.2 mg) or diluted sheep serum (2.2 mg protein) was introduced daily via an indwelling catheter into the uterine lumen of 3 ewes for 7 days (days 12-18). Peripheral blood samples were collected daily for 14 days (days 12-25). On day 25 all ewes were laparotomized and ovaries observed to determine whether CL previously marked with India ink were maintained. All controls had ovulated, and formed new cL. By contrast none of the conceptus protein-treated ewes had ovulated, and their peripheral progesterone levels remained elevated. One ewe maintained a functional CL until day 52 when she was hysterectomized. Light microscopy of histological sections prepared from the endometrium revealed glandular development comparable to that in the endometrium of cyclic animals during late diestrus. The cells of the CL were similar to those from cyclic animals during mid- to late diestrus. Ovine trophoblast protein (oTP-1), a major protein secreted by the sheep conceptus between days 13 and 21 of pregnancy, was purified from conceptus incubation medium and injected (0.2 mg protein/day) into the uterine lumen of 3 animals. Plasma progesterone concentrations indicated that oTP-1-treated animals maintained luteal function 4 days longer than did control animals. Evidently, conceptus proteins and specifically oTP-1 are involved in the maintenance of luteal function during early pregnancy, and this action is probably mediated through interaction with the uterine endometrium.