Changes in calcium levels in the endometrium throughout pregnancy and the role of calcium on endometrial gene expression at the time of conceptus implantation in pigs

Choi, Yohan; Jang, Hyejeong; Seo, Heewon; Yoo, Inkyu; Han, Jisoo; Kim, Minjeong; Lee, Soohyung; Ka, Hakhyun

doi:10.1002/mrd.23166

Cited by 24 publications

(12 citation statements)

References 48 publications

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“…Studies in both pigs and sheep indicate that calcium and phosphate increase in uterine flushings during the peri-implantation period of pregnancy, and are more abundant in uterine flushings from pregnant than cyclic animals during the mid-luteal phase of the estrous cycle [ 18 , 19 , 27 , 28 ]. Further, temporal changes in the abundance of minerals in the uterine lumen during the peri-implantation period are accompanied with striking alterations in the expression of molecules with regulatory roles in phosphate, calcium, and vitamin D transport and signaling [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

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

Stenhouse

Newton

Halloran

et al. 2023

J Animal Sci Biotechnol

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Background Recent evidence suggests important roles for progesterone (P4) and interferon tau in the regulation of calcium, phosphate, and vitamin D signaling in the uteri of pregnant sheep. However, the effects of P4 and estradiol (E2), with respect to the expression of their receptors PGR and ESR1, respectively, in uterine epithelia on mineral signaling during the estrous cycle has not been investigated. Estrous cycles of mature Suffolk ewes were synchronized, prostaglandin F2α was administered, and ewes were observed for estrus (designated as Day 0) in the presence of vasectomized rams. On Days 1, 9, or 14 of the estrous cycle, hysterectomies were performed. Results 25-hydroxyvitamin D was more abundant in plasma from ewes on Day 14 than Day 1 (P < 0.05). Expression of fibroblast growth factor receptor 2 (FGFR2), a disintegrin and metalloprotease 17 (ADAM17), and parathyroid hormone-related protein (PTHrP) mRNAs was greater in endometria on Day 9 compared to Days 1 and 14 (P < 0.01). Similarly, expression of transient receptor potential cation channel subfamily V member 6 (TRPV6) mRNA was greater in endometria on Day 9 than Day 1 (P < 0.05). ATPase plasma membrane Ca2+ transporting 4 (ATP2B4) and S100 calcium binding protein G (S100G) mRNA expression was greater in endometria on Day 14 than on Days 1 and 9 (P < 0.01). In contrast, endometrial expression of vitamin D receptor (VDR) mRNA was lower on Days 9 and 14 than Day 1 (P < 0.01). Expression of klotho (KL) (P < 0.05) and cytochrome P450 family 24 subfamily A member 1 (CYP24) (P < 0.01) mRNAs was lower on Day 14 than Days 1 and 9. ADAM17, FGF23, CYP2R1, CYP27B1, KL, and VDR proteins immunolocalized to the uterine myometrium, blood vessels, and uterine luminal (LE), superficial glandular (sGE), and glandular (GE) epithelia. S100A9 protein was weakly expressed in the uterine myometrium, LE, sGE, and GE. Immunoreactivity of CYP2R1 and KL proteins in uterine LE and sGE was less on Day 1 than on Days 9 and 14. In contrast, S100G protein was expressed exclusively by GE, and immunoreactive S100G protein was less on Day 9. S100A12 protein localized to stromal cells of the uterine stratum spongiosum and blood vessels, but not by uterine epithelial cells. Conclusion Collectively, these results implicate E2, P4, and PGR in the regulation of phosphate, calcium, and vitamin D signaling in cyclic ewes.

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Section: Introductionmentioning

confidence: 99%

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

Stenhouse

Newton

Halloran

et al. 2023

J Animal Sci Biotechnol

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“…Calcium ions are key regulators for both embryo implantation and microvilli formation, and they can provide a greater surface area on the apical side of the cells; thus allowing asymmetric localization of membrane transporters, cytoskeletal proteins, and enzymes on EECs, eventually enhancing cell polarity [35]. Previous studies have revealed that blocking endometrial calcium channels can cause complete implantation failure in mice during the implantation window stage [43].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the mRNA expression of proliferation-related PCNA in the EEC in the HS treatment group was remarkably lower than that in the control group (Figure 7C). MUC1 and ZO-1 have been reported to be related to embryo implantation and cell adhesion [35,36]. The cultured porcine endometrial epithelial cells exposed to heat stress at 42 • C for 0 h were used as a control to obtain the relative mRNA expression of MUC1 and ZO-1.…”

Section: Effects Of Heat Stress On Porcine Endometrial Epithelial Cellsmentioning

confidence: 99%

Heat Stress Impairs Maternal Endometrial Integrity and Results in Embryo Implantation Failure by Regulating Transport-Related Gene Expression in Tongcheng Pigs

et al. 2022

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Heat stress (HS) poses a significant threat to production and survival in the global swine industry. However, the molecular regulatory effects of heat stress on maternal endometrial cells are poorly understood in pigs during early embryo implantation. In this study, we systematically examined morphological changes in the endometrium and the corresponding regulation mechanism in response to HS by combining scanning electron microscopy (SEM), hematoxylin/eosin (H&E) staining, western blot, and RNA-seq analyses. Our results showed that HS led to porcine endometrium damage and endometrial thinness during embryo implantation. The expression levels of cell adhesion-related proteins, including N-cadherin and E-cadherin, in the uterus were significantly lower in the heat stress group (39 ± 1 °C, n = 3) than in the control group (28 ± 1 °C, n = 3). A total of 338 up-regulated genes and 378 down-regulated genes were identified in porcine endometrium under HS. The down-regulated genes were found to be mainly enriched in the pathways related to the microtubule complex, immune system process, and metalloendopeptidase activity, whereas the up-regulated genes were mainly involved in calcium ion binding, the extracellular region, and molecular function regulation. S100A9 was found to be one of the most significant differentially expressed genes (DEGs) in the endometrium under HS, and this gene could promote proliferation of endometrial cells and inhibit their apoptosis. Meanwhile, HS caused endometrial epithelial cell (EEC) damage and inhibited its proliferation. Overall, our results demonstrated that HS induced uterine morphological change and tissue damage by regulating the expression of genes associated with calcium ions and amino acid transport. These findings may provide novel molecular insights into endometrial damage under HS during embryo implantation.

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“…During implantation, the trophoblast cells in the blastocyst create tissue and physiological connections with the endometrial epithelium, which stabilize the development of the blastocyst in the uterus [ 7 , 8 ]. The critical phase in pigs is day 12 of gestation (gd12), whereby the embryonic morphology changes dramatically from tubular to filamentous, accompanied by the secretion of large amounts of estrogen and interleukins; estrogen levels peak on gd12 and can be harnessed to validate pregnancy to facilitate embryo implantation [ 9 , 10 , 11 ]. Given that the porcine embryo floats in the uterine luminal fluid (ULF) before implantation, the ULF serves as a necessary route of maternal–fetal interaction, and extracellular vesicles (EVs) in the ULF participate in information transmission [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of miR-143-3p from Extracellular Vesicles of Porcine Uterine Luminal Fluid on Porcine Trophoblast Cells

Ding

Gan

et al. 2022

Animals

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Extracellular vesicles (EVs) in uterine luminal fluid (ULF) can reportedly affect the proliferation and migration function of porcine trophoblast cells (PTr2 cells) by mediating the maternal–fetal exchange of information. miR-143-3p is considered a crucial miRNA in early pregnancy in mammals; however, little is currently known about how it regulates the function of PTr2 cells. This study aimed to investigate the effects of ssc-miR-143-3p in ULF-EVs on the function of PTr2 cells during porcine embryo implantation. The uptake of ULF-EVs by PTr2 cells was confirmed, which significantly increased the expression of ssc-miR-143-3p. Ssc-miR-143-3p was found to facilitate the proliferation and migration of PTr2 cells in the CCK-8, EdU and wound-closure assays, while the opposite findings were observed after the knockdown of ssc-miR-143-3p. Bioinformatics analysis and the luciferase reporter assay showed that glycerol-3 phosphate dehydrogenase 2 (GDP2) was directly targeted by miR-143-3p. Inhibition of miR-143-3p was validated in mice to inhibit embryo implantation. In summary, ssc-miR-143-3p in ULF-EVs affects the proliferation and migration of PTr2 cells by mediating GPD2, thereby affecting embryo implantation.

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Changes in calcium levels in the endometrium throughout pregnancy and the role of calcium on endometrial gene expression at the time of conceptus implantation in pigs

Cited by 24 publications

References 48 publications

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

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

Heat Stress Impairs Maternal Endometrial Integrity and Results in Embryo Implantation Failure by Regulating Transport-Related Gene Expression in Tongcheng Pigs

Effect of miR-143-3p from Extracellular Vesicles of Porcine Uterine Luminal Fluid on Porcine Trophoblast Cells

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