What regulates placental steroidogenesis in 90-day pregnant ewes?

By day-90, the placenta secretes half of the circulating progesterone and 85% of the circulating estradiol-17β [Weems YS, Vincent D, Tanaka Y, et al. Effects of prostaglandin F2α on sources of progesterone and pregnancy in intact, ovariectomized, and hysterectomized 90-100 day pregnant ewes. Prostaglandins 1992;43:203-22; Weems YS, Vincent DL, Nusser K, et al. Effects of prostaglandin F2α (PGF2α) on secretion of estradiol-17β and cortisol in 90-100 day hysterectomized, intact, or ovariectomized pregnant ewes. Prostaglandins 1994;48:139-57]. Ovariectomy (OVX) or prostaglandin (PG) F2α (PGF2α) does not abort intact or OVX 90-day pregnant ewes and PGF2α regresses the corpus luteum, but does not affect placental progesterone secretion in vivo [Weems YS, Vincent D, Tanaka Y, et al. Effects of prostaglandin F2α on sources of progesterone and pregnancy in intact, ovariectomized, and hysterectomized 90-100 day pregnant ewes. Prostaglandins 1992;43:203-22]. Luteal progesterone secretion in vitro at day-90 of pregnancy in ewes is regulated by PGE1 and/or PGE2, not by ovine luteinizing hormone (LH; 3). Concentrations of PGE in uterine or ovarian venous plasma averaged 6 ng/ml at 90-100 days of pregnancy in ewes [Weems YS, Vincent DL, Tanaka Y, Nusser K, Ledgerwood KS, Weems CW. Effect of prostaglandin F2α on uterine or ovarian secretion of prostaglandins E and F2α (PGE; PGF2α) in vivo in 90-100 day hysterectomized, intact or ovariectomized pregnant ewes. Prostaglandins. 1993;46:277-96]. Ovine placental PGE secretion is regulated by LH up to day-50 and by pregnancy specific protein B (PSPB) after day-50 of pregnancy [Weems YS, Kim L, Humphreys V, Tsuda V, Weems CW. Effect of luteinizing hormone (LH), pregnancy specific protein B (PSPB), or arachidonic acid (AA) on ovine endometrium of the estrous cycle or placental secretion of prostaglandins E2 (PGE2) and F2α (PGF2α), and progesterone in vitro. Prostaglandins Other Lipid Mediators 2003;71:55-73]. Indomethacin (INDO), a prostaglandin synthesis inhibitor [Lands WEM. The biosynthesis and metabolism of prostaglandins. Annu Rev Physiol 1979;41:633-46], lowers jugular venous progesterone [Bridges PJ, Weems YS, Kim L, et al. Effect of prostaglandin F2α (PGF2α), indomethacin, tamoxifen or estradiol-17β on pregnancy, progesterone and pregnancy specific protein B (PSPB) secretion in 88-90 day pregnant ewes. Prostaglandins Other Lipid Mediators 1999;58:113-24] and inferior vena cava PGE of pregnant ewes with ovaries by half at day-90 [Bridges PJ, Weems YS, Kim L, LeaMaster BR, Vincent DL, Weems CW. Effect of prostaglandin F2α (PGF2α), indomethacin, tamoxifen or estradiol-17β on prostaglandin E (PGE), PGF2α and estradiol-17β secretion in 88-90 day pregnant sheep. Prostaglandins Other Lipid Mediators 1999;58:167-78]. In addition, treatment of 90 day ovine diced placental slices with androstenedione in vitro increased placental estradiol-17β, but treatment with PGF2αin vitro did not decrease placental progesterone secretion, which indicates that ovine placenta progesterone secretion is resistant to the luteolytic action of PGF2α [Weems YS, Bridges PJ, LeaMaster BR, Sasser RG, Vincent DL, Weems CW. Secretion of progesterone, estradiol-17β, prostaglandins (PG) E (PGE), F2α (PGF2α), and pregnancy specific protein B (PSPB) by day 90 intact or ovariectomized pregnant ewes. Prostaglandins Other Lipid Mediators 1999;58:139-48]. This also explains why ovine uterine secretion of decreased around day-50 [Weems YS, Kim L, Humphreys V, Tsuda V, Weems CW. Effect of luteinizing hormone (LH), pregnancy specific protein B (PSPB), or arachidonic acid (AA) on ovine endometrium of the estrous cycle or placental secretion of prostaglandins E2 (PGE2) and F2α (PGF2α), and progesterone in vitro. Prostaglandins Other Lipid Mediators 2003;71:55-73], when placental estradiol-17β secretion is increasing [Weems C, Weems Y, Vincent D. Maternal recognition of pregnancy and maintenance of gestation in sheep. In: Reproduction and animal breeding: advances and strategies. Enne G, Greppi G, Lauria A, editors, Elsevier Pub., Amsterdam 1995. p. 277-93]. Treatment of 90 day pregnant ewes with estradiol-17β+ PGF2α, but not either treatment alone, caused a linear increase in both estradiol-17β and PGF2α and ewes were aborting [Bridges PJ, Weems YS, Kim L, Sasser RG, LeaMaster BR, Vincent DL, Weems CW. Effect of prostaglandin F2α (PGF2α), indomethacin, tamoxifen or estradiol-17β on pregnancy, progesterone and pregnancy specific protein B (PSPB) secretion in 88-90 day pregnant ewes. Prostaglandins Other Lipid Mediators 1999;58:113-24; Bridges PJ, Weems YS, Kim L, LeaMaster BR, Vincent DL, Weems CW. Effect of prostaglandin F2α (PGF2α), indomethacin, tamoxifen or estradiol-17β on prostaglandin E (PGE), PGF2α and estradiol-17β secretion in 88-90 day pregnant sheep. Prostaglandins Other Lipid Mediators 1999;58:167-78]. Pregnant ewes OVX on day 83 of pregnancy and placental slices cultured in vitro secretes 2-3-fold more estradiol-17β, PSPB, PGE, and progesterone than placental slices from 90 day intact pregnant ewes, but placental PGF2α secretion by placental slices from intact or OVX ewes did not change [Denamur R, Kann G, Short R V. How does the corpus luteum of the sheep know that there is an embryo in the uterus? In: Pierrepont G, editor. Endocrinology of pregnancy and parturition, vol. 2. Cardiff, Wales, UK: Alpha Omega Pub Co.; 1973. p. 4-38]. The objective of these experiments was to determine what regulates ovine placental progesterone and estradiol-17β secretion at day-90 of pregnancy, since the hypophysis [Casida LE, Warwick J. The necessity of the corpus luteum for maintenance of pregnancy in the ewe. J Anim Sci 1945;4:34-9] or ovaries [Weems CW, Weems YS, Randel RD. Prostaglandins and reproduction in female farm animals. Vet J 2006;171:206-28] are not necessary after day-55 to maintain pregnancy. In Experiment 1, diced placental slices from day-90 intact or OVX pregnant ewes that were ovariectomized or laparotomized and ovaries were not removed on day 83 were collected on day-90 and incubated in vitro in M-199 with Vehicle, ovine luteinizing hormone (oLH), ovine follicle stimulating hormone (oFSH), ovine placental lactogen (oPL), PGEl, PGE2, PGD2, PGI2, insulin-like growth factor (IGF) 1 or 2 (IGFl; IGF2), leukotriene C4 (LTC4), platelet activating factor (PAF) 16 or 18 (PAF-16; PAF-18) at doses of 0, 1, 10, or 100 ng/ml for 4 h. In Experiment 2, placental slices from day-90 intact and OVX (intact or OVX laporotomized 7 days earlier) pregnant ewes were incubated in vitro with vehicle, INDO, Meclofenamate (MECLO), PGEl, PGE2, INDO + PGE1, MECLO + PGEl, INDO + PGE2, or MECLO + PGE2 for 4 h. Media were analyzed for progesterone, estradiol-17β, PGE, or PGF2α by RIA. Hormone data in media were analyzed in Experiment 1 by a 2 × 3 × 13 and in Experiment 2 by a 2 × 9 Factorial Design for ANOVA. In Experiment 1, placental progesterone, PGE, or estradiol-17β secretion were increased (P ≤ 0.05) two-fold by OVX. Progesterone was not increased (P ≥ 0.05) by any treatment other than OVX and only FSH increased (P ≤ 0.05) estradiol-17β secretion by placental slices in both OVX and intact ewes 90-day pregnant ewes. In Experiment 2, INDO or MECLO decreased (P ≤ 0.05) placental progesterone secretion by 88% but did not decrease (P ≥ 0.05) placental estradiol-17β secretion from intact or OVX ewes. PGEl or PGE2 increased (P ≤ 0.05) progesterone secretion only in ewes treated with INDO or MECLO. It is concluded that FSH probably regulates day-90 ovine placental estradiol-17β secretion, while PGEl or PGE2 regulates day-90 placental progesterone secretion.