Effects of exogenous progesterone on the expression of mineral regulatory molecules by ovine endometrium and placentomes

Abstract

This study aimed to determine whether the acceleration of conceptus development induced by administration of exogenous progesterone (P4) during the pre-implantation period of pregnancy alters calcium, phosphate, and vitamin D signaling at the maternal-conceptus interface. Suffolk ewes (n = 48) were mated to fertile rams and received daily intramuscular injections of either corn oil vehicle (CO) or 25 mg progesterone in CO (P4) for the first 8 days of pregnancy and hysterectomized on either Day 9 (CO n = 5; P4 n = 6), 12 (CO n = 9; P4 n = 4) or 125 (CO n = 14; P4 n = 10) of gestation. Expression of S100A12 (P < 0.05) and FGFR2 (P < 0.01) mRNAs was lower in endometria from P4-treated ewes on Day 12. Expression of ADAM10 (P < 0.05) mRNA was greater in endometria from P4-treated ewes on Day 125. Expression of ADAM10 (P < 0.01), FGFR2 (P < 0.05), SLC20A1 (P < 0.05), TRPV5 (P < 0.05), and TRPV6 (P < 0.01) mRNAs was greater, but KL mRNA expression was lower (P < 0.05) in placentomes from P4-treated ewes at Day 125. There was lower endometrial and greater placentomal expression of mRNAs involved in mineral metabolism and transport in twin compared to singleton pregnancies. Further, expression of mRNAs involved in mineral metabolism and transport was greater in P4-treated twin placentomes. KL, FGF23, VDR, S100A9, S100A12, S100G, and CYP27B1 proteins were immunolocalized in endometria and placentomes. Exogenous P4 in early pregnancy altered expression of regulators of calcium, phosphate, and vitamin D on Day 125 of pregnancy indicating a novel effect of P4 on mineral transport at the maternal-conceptus interface.

Phosphate, calcium, and vitamin D signaling, transport, and metabolism in the endometria of cyclic ewes

“…Results of our recent investigations indicate regulatory roles for P4 and IFNT, both alone and synergistically, to affect expression of regulators of calcium, phosphate, and vitamin D signaling, transport, and metabolism in the ovine endometrium in pseudo pregnant ewes [ 29 ]. Further, treatment of ewes with exogenous P4 during the pre-implantation period of pregnancy had long-term effects on mineral signaling in both endometria and placentomes in late gestation [ 33 ]. However, the effects of changes in E2, ESR1, P4, and PGR on expression of mRNAs and proteins critical for mineral signaling in the endometria of sheep are poorly understood.…”

“…It is important to note that FGF23 not only localizes to uterine epithelial cells, but also localizes to some uterine stromal cells. Ewes treated with exogenous P4 had lower expression of FGFR2 mRNA than controls on Day 12 of gestation [ 33 ]. Further, endometrial expression of FGFR2 mRNA expression decreases in pregnant ewes between Days 12 and 17 [ 18 ].…”

“…The concentrations of 25(OH)D in plasma and endometrial homogenates were quantified by ELISA (Eagle Biosciences, Amherst, NH, USA; VID91-K01), as described previously [ 33 ]. Absorbance was read on a spectrophotometric plate reader (SynergyH1, BioTek) at 450 nm.…”

Uptake of Phosphate, Calcium, and Vitamin D by the Pregnant Uterus of Sheep in Late Gestation: Regulation by Chorionic Somatomammotropin Hormone

“…It has been suggested that, in pregnant ewes, the placenta is responsible for the generation of approximately 40% of the 1,25-dihydroxycholecalciferol in fetal blood and that local metabolism of vitamin D in the pregnant uterus is critical for the regulation of fetal growth. In fact, the cytochrome P450 (CYP) enzymes critical for the metabolism of vitamin D, and the vitamin D receptor, are expressed at the maternal-conceptus interface in late gestation (Day 125) in sheep [ 17 , 20 ]. This finding is not unique to sheep as the expression of vitamin D regulatory molecules in the female reproductive tract in pigs, humans, and rodents has been reported [ 39 , 40 , 41 , 42 ], suggesting important roles of vitamin D in the establishment and maintenance of pregnancy, and in the regulation of conceptus growth and development.…”

“…It has been suggested that interferon tau (IFNT), the maternal signal for pregnancy recognition in ruminants, and progesterone (P4) act both independently and synergistically to alter endometrial expression of mRNAs and proteins important for calcium, phosphate, and vitamin D signaling, transport, and utilization during the peri-implantation period of pregnancy [ 19 ]. Furthermore, it was recently reported that exogenous P4 supplementation for the first eight days of pregnancy altered expression of mRNAs and proteins of regulators of calcium, phosphate, and vitamin D signaling, transport, and utilization in both the endometrium and placentomes on Day 125 of pregnancy [ 20 ]. While these studies have provided compelling evidence for endocrine (P4) and paracrine (IFNT) regulation of mineral transport in the pregnant ewe, other conceptus (embryo/fetus and associated extra-embryonic membranes) derived signals may be important regulators of phosphate, calcium, and vitamin D signaling, transport, and utilization at the maternal-conceptus interface.…”