In sheep or cattle, 30 - 40% of cows or ewes bred to a single mating will not become pregnant.  Seventy percent of this loss occurs during early pregnancy, while 30% of the lost pregnancies occur later.  In sheep, 10 percent of ewes diagnosed pregnant at 60 days of the 150 day pregnancy lose their fetuses.  Thus far, we have learned 8 significant pieces of information concerning the corpus luteum, placenta, and secretion of progesterone, pregnancy specific protein B (PSPB), estradiol-17ß, prostaglandin E2 (PGE2) and prostaglandin F2a (PGF2a ) during pregnancy using sheep and cattle.  The corpus luteum of pregnancy at 90 days in sheep or 200 days in cattle, is no longer capable of responding to luteinizing hormone (LH) as a luteotropin to stimulate progesterone secretion, although progesterone is required throughout gestation to maintain pregnancy.  Instead, the corpus luteum responds to PGE2 as a luteotropin to regulate secretion of progesterone.   The PGE2 regulating secretion of progesterone by the corpus luteum of pregnancy comes from the corpus luteum.  Regulation of PGE2 secretion by the corpus luteum at 90 days in sheep or 200 days in cattle is by PSPB from the placenta.  PSPB also regulates placental secretion of progesterone in cows and sheep and indomethacin, an inhibitor of PBE2 secretion, decreases progesterone secretion by the CL or placenta in vitro or in vivo.   Since the maternal pituitary is the source of LH and is no longer needed after day 50 of pregnancy, these data suggest the corpus luteum of the estrous cycle is converted to the corpus luteum of pregnancy but undergoes a series of developmental changes.  PSPB is secreted  by day 13 ovine or day 16 bovine embryos (Garth Sasser, U. of Idaho).   We suggest that PSPB is an initial trigger to convert the corpus luteum of the estrous cycle to the corpus luteum of pregnancy, which no longer needs LH after day 50 in sheep and uses PGE2 as the luteotropin of pregnancy after day 50. 

Stress increases secretion of PSPB and the only source of PSPB is the placenta.  Estradiol-17ß appears to regulate placental secretion of PSPB.   Ninety percent of the circulating estradiol-17ß at 90 days of pregnancy in sheep is from the placenta.  However, when estradiol-17ß and PGF2a are given every 6 hours together, endogenous estradiol-17ß and PGF2a   are increased linearly and pregnancies are lost in sheep.  Thus, estradiol-17ß is both beneficial and detrimental to the success of the pregnancy.