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Teolytic signal in the horse conceptus thus differs from domestic ruminants and pigs. In 1989, Sharp et al.  published evidence that the antiluteolytic agent secreted by the TAK-385 manufacturer equine conceptus has a molecular weight between 1,000 and 6,000. However, molecules fitting into this molecular mass like PGE2 or insulin failed to prolong lifespan of the corpus luteum in cyclic mares when infused into the uterine lumen [5, 17]. Development of an endometrial explant in vitro culture system appeared promising to support further research for identification and characterization of the equine conceptus factor responsible for maternal recognition of pregnancy . Unfortunately further relevant results have not been published. Before and on day 14 of pregnancy, the equine yolk sac produces a characteristic pattern of proteins thatcompletely changes thereafter. It was suggested that one or more of these proteins might be involved in jir.2014.0227 the anti-luteolytic mechanism of the horse conceptus , but this has never been proven. The switch in protein expression by the yolk sac around day 14 is most likely associated with development of the mesoderm with its blood-forming islets [3, 18]. Uterocalin which has mainly received consideration as an endometrial protein (see below) is also expressed in conceptus tissue with decreasing expression between days 8 and 14 of pregnancy . Persistence of the corpus luteum is also seen in a certain percentage of non-pregnant mares after introduction of a glass marble  or fluid-filled rubber ball  into the uterine lumen during the first days after ovulation. The presence of a spherical intrauterine device has thus been suggested to resemble the presence of a conceptus by exerting contact or pressure directly on the uterine wall . This may induce changes in the endometrial epithelia similar to those induced by presence of a conceptus. Interestingly, the effect seems to depend on adequate perfusion and drainage of the endometrium and is less effective in aged mares . These results suggest that the embryonic signal for maternal recognition of pregnancy in the horse might be at least in part mechanical rather than secretory in origin. This assumption was further supported by modulation of prostaglandin production and prolonged corpus luteum lifespan reported after intrauterine administration of different plant oils into the uterine lumen of luteal phase mares . The authors could not exclude the possibility that physical interference with the endometrium was involved in this phenomenon. However, in contradiction to this hypothesis, intrauterine administration of mineral oil did not prevent luteolysis.Sources of progestin during equine pregnancyIn domestic animal species, pregnancy is maintained by secretion of progesterone from the corpus luteum, the placenta or a combination of both. The situation is more complicated in pregnant mares where not only different sources for progestin secretion exist, but also a variety of progestins as well as estrogens are secreted [24, 25]. From ovulation until approximately day 40 of pregnancy, progestins fpsyg.2017.00007 and estrogens are solely secreted from the primary corpus luteum [26?9]. Besides progesterone the progestins 5-pregnane-3,20-dione and 3-hydroxy5-pregnan-20-one are detectable in the circulation . Progestin concentrations in blood of mares increase rapidly after ovulation and peak around day 5 of pregnancy. From then onwards concentrations in maternal plasma gradually.