Effects of LPA2, LPA3, EP1, 2, 3 and 4, sirtuins, 1, 2 and 3, or estradiol-17β receptor agonists or antagonists on luteal or endometrial function in ewes

Laporte, Magen Elizabeth
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[Honolulu] : [University of Hawaii at Manoa], [December 2010]
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Loss of luteal progesterone secretion is due to endometrial secretion of PGF2α in ewes. Secretion, transport, and binding of PGF2α are not reduced during early pregnancy in ewes. Instead, the ovine embryo imparts resistance to the luteolytic effects of PGF2α, causing an increase in PGE1 and PGE2 in the endometrium and uterine venous plasma during early pregnancy. Sirtuins 1, 2 and 3 are histone deacetylase proteins and regulators of lifespan, apoptosis, transcription and energy metabolism that are proposed to alter prostaglandin synthesis. LPA receptor signaling has been implicated in the regulation of implantation timing and prostaglandin secretion in mice. The objective of experiment 1 was to determine whether treatment with LPA2, LPA3 and EP4 receptor agonists affected luteal weights, circulating progesterone, luteal mRNA for LH receptors, and luteal occupied and unoccupied receptors for LH in vivo. Day-10 non-pregnant ewes received a single injection of vehicle, DP (LPA2 agonist), OMPT (LPA3 agonist), or CAY10580 (EP4 agonist) into the interstitial tissue of the ovarian vascular pedicle adjacent to the luteal-containing ovary. Jugular venous blood was collected every hour for the first six hours and every six hours thereafter until 48 hours for analysis of progesterone by RIA. At 48 hours corpora lutea were collected, weighed, and frozen in liquid nitrogen until analysis for mRNA for LH receptors and occupied and unoccupied receptors for LH. DP, OMPT, and CAY10580 did not affect luteal weights, circulating concentrations of progesterone, or occupied receptors for LH in ovine luteal tissue. DP and CAY10580, but not OMPT, increased (P ≤ 0.05) luteal mRNA for LH receptors compared to vehicle. DP, OMPT, and CAY10580 increased (P ≤ 0.0001) luteal unoccupied receptors for LH compared to vehicle. The objective of experiment 2 was determine whether LPA, LPA receptor agonists, EP receptor agonists, estradiol-17β receptor agonists or antagonists, sirtuins, sirtuin activators and TNF-α affected secretion of progesterone, PGF2α, or PGE in luteal or endometrial tissue in vitro. Corpora lutea and endometrial caruncles were collected on day-12 postestrus, weighed, diced, and incubated in vitro for 1 hour in the absence of treatments and for four and eight hours with treatments. Media collected at four and eight hours were stored at-20°C until analysis of progesterone, PGF2α, or PGE by RIA. None of the treatments tested in vitro affected luteal secretion of progesterone or PGF2α. CAY10580 increased (P ≤ 0.0001) PGE secretion by ovine luteal tissue in vitro and tended to decrease (P = 0.066) PGF2α. CAY10580 increased (P ≤ 0.0001) PGE secretion by ovine endometrial caruncles in vitro, but did not affect PGF2α. Sirtuin-1 increased (P ≤ 0.0001) PGE secretion by caruncles in vitro at eight hours compared to vehicle at eight hours. EP4 receptors may mediate the antiluteolytic/luteotropic effects of PGE1 and PGE2 by increasing the ratio of PGE: PGF2α secreted by ovine corpora lutea and endometrial caruncles. LPA2 and LPA3 receptor agonists do not appear to regulate progesterone secretion by ovine luteal tissue in vivo or in vitro or prostaglandin secretion by ovine luteal and endometrial tissue in vitro.
M.S. University of Hawaii at Manoa 2010.
Includes bibliographical references.
ewes, luteal function, endometrial function
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Theses for the degree of Master of Science (University of Hawaii at Manoa). Animal Sciences.
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