PHYSIOLOGY OF PREGNANCY MAINTENANCE

Gestation in the cow extends 270 to 292 days after breeding. Once conception has occurred, progesterone is essential for pregnancy maintenance. Both luteal and extraovarian sources of progesterone must be eliminated for successful induction of abortion. Although the maternal endocrine events of the first 15 days of cycle and of pregnancy are similar, the conceptus secretes a range of products, including steroids, prostaglandins, and proteins, beginning at 12 to 13 days of gestation. At least one of these products, interferon-γ, results in maternal recognition of pregnancy by inhibition of luteolysis and prolonged luteal lifespan.¹^–³ These effects are mediated by attenuation of endogenous prostaglandin F₂ alpha (PGF_2α) secretion.⁴

The functional life of the corpus luteum (CL) is controlled by a balance of luteotropic factors, including luteinizing hormone, and luteolytic factors, including PGF_2α. PGF_2α is the naturally occurring luteolysin, acting both directly and indirectly on the CL. PGF_2α may cause local vasoconstriction of luteal blood flow; however, PGF_2α receptors are present on luteal cells, and PGF_2α has a direct effect on luteal progesterone secretion.⁵ Endogenous luteolysis occurs in response to a cascade of hormonal events that result in pulsatile PGF_2α secretion. It has been proposed that as part of this cascade, estradiol induces oxytocin receptors on endometrial cells.⁶ Oxytocin activates those receptors, resulting in the synthesis and secretion of PGF_2α.

Peripheral progesterone levels fluctuate between 6 and 15 ng/mL throughout gestation,⁷ with a gradual decline in the 2 to 4 weeks preceding parturition.⁸ Pregnant cows that undergo ovariectomy before the first 3 to 5 months of gestation will abort. In cows ovariectomized after 200 days of gestation, progesterone secretion is maintained, although at significantly lower levels than before ovariectomy.⁹ These cows do not abort, but parturition is advanced by 2 weeks and may be accompanied by dystocia and retained fetal membranes. The adrenal gland may contribute 1 to 4 ng/mL of progesterone.¹⁰

In summary, progesterone is luteal in origin for the first 150 days of gestation. Between 150 and 250 days, the placenta acts as additional source of progesterone. In the final month of gestation, placental progesterone declines and pregnancy is again dependent on luteal progesterone. Successful treatment to induce abortion must lower circulating progesterone below 1 ng/mL, which is the threshold necessary to maintain pregnancy,¹¹ and must be directed specifically at the source of progesterone appropriate for the stage of gestation at the time of treatment.