• Asian-Australasian Journal of Animal Sciences
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• v.32 no.9
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• pp.1355-1362
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• 2019

Objective: S100A7A, a member of the S100 protein family, is involved in various biological processes, including innate immunity, antimicrobial function, and epithelial tumorigenesis. However, the expression and function of S100A7A in the endometrium during the estrous cycle and pregnancy are not well understood in pigs. Therefore, this study determined the expression and regulation of S100A7A at the maternal-conceptus interface in pigs. Methods: We obtained endometrial tissues from pigs throughout the estrous cycle and pregnancy, conceptus tissues during early pregnancy, and chorioallantoic tissues during midto late pregnancy and analyzed the expression of S100A7A in these tissues. We also determined the effects of steroid hormones, estradiol-$17{\beta}$ ($E_2$) and progesterone, and interleukin-$1{\beta}$ (IL1B) on S100A7A expression in endometrial tissues. Results: We found that S100A7A was expressed in the endometrium during the estrous cycle and pregnancy in a pregnancy status- and stage-dependent manner and was localized to endometrial luminal epithelial (LE) and superficial glandular epithelial cells with strong intensity in LE cells on day 12 of pregnancy. Early stage conceptuses and chorioallantoic tissues from day 30 to term pregnancy also expressed S100A7A. The expression of S100A7A was increased by $E_2$ and IL1B in endometrial tissues. Conclusion: S100A7A was expressed at the maternal-conceptus interface at the initiation of implantation in response to conceptus-derived estrogen and IL1B and could be a unique endometrial epithelial marker for conceptus implantation in pigs. These findings provide an important insight into the understanding of conceptus-endometrial interactions for the successful establishment of pregnancy in pigs.

• Animal Bioscience
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• v.35 no.4
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• pp.533-543
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• 2022

Objective: Caspase-mediated apoptosis plays a crucial role in the regulation of endometrial and placental function in females. Caspase activity is tightly controlled by members of the inhibitors of apoptosis proteins (IAPs) family. However, the expression and regulation of IAPs at the maternal-conceptus interface has not been studied in pigs. Therefore, we determined the expression of IAP family members baculovirus IAP repeat-containing 1 (BIRC1) to BIRC6 at the maternal-conceptus interface in pigs. Methods: We obtained endometrial tissues from pigs at various stages of the estrous cycle and pregnancy, conceptus tissues during early pregnancy, and chorioallantoic tissues during mid- to late pregnancy and analyzed the expression of IAPs. Furthermore, we determined the effects of the steroid hormones estradiol-17β (E2) and progesterone on the expression of IAPs in endometrial explant tissue cultures. Results: During the estrous cycle, BIRC2 and BIRC5 expression varied cyclically, and during pregnancy, endometrial BIRC1, BIRC2, BIRC3, BIRC4, and BIRC5 expression varied in a stage-specific manner. Conceptus and chorioallantoic tissues also expressed IAPs during pregnancy. The BIRC2 and BIR3 mRNAs were localized to luminal epithelial cells, and BIRC4 proteins to glandular epithelial cells in the endometrium. Exposure of endometrial tissues to E2 increased the expression of BIRC6, while progesterone increased the expression of BIRC1, BIRC4, and BIRC6 in a dose-dependent manner. Conclusion: These results indicated that IAPs were expressed in the endometrium during the estrous cycle and at the maternal-conceptus interface during pregnancy in a stage-specific manner. In addition, steroid hormones were found to be responsible for the expression of some IAPs in pigs. Together, the results suggested that IAPs may play important roles in endometrial and placental functions by regulating caspase action and apoptosis at the maternal-conceptus interface.

• Animal Bioscience
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• v.36 no.7
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• pp.1034-1043
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• 2023

Objective: Two serine protease inhibitors, peptidase inhibitor 3 (PI3) and secretory leukocyte protease inhibitor (SLPI), play important roles in protease inhibition and antimicrobial activity, but their expression, regulation, and function at the maternal-fetal interface in pigs are not fully understood. Therefore, we determined the expression and regulation of PI3 and SLPI in the endometrium throughout the estrous cycle and at the maternal-fetal interface in pigs. Methods: Endometrial tissues during the estrous cycle and pregnancy, conceptus tissues during early pregnancy, and chorioallantoic tissues during mid to late pregnancy were obtained, and the expression of PI3 and SLPI was analyzed. The effects of the steroid hormones estradiol-17β (E2) and progesterone (P4) on the expression of PI3 and SLPI were determined in endometrial explant cultures. Results: PI3 and SLPI were expressed in the endometrium during the estrous cycle and pregnancy, with higher levels during mid to late pregnancy than during the estrous cycle and early pregnancy. Early-stage conceptuses and chorioallantoic tissues during mid to late pregnancy also expressed PI3 and SLPI. PI3 protein and SLPI mRNA were primarily localized to endometrial epithelia. In endometrial explant cultures, the expression of PI3 was induced by increasing doses of P4, and the expression of SLPI was induced by increasing doses of E2 and P4. Conclusion: These results suggest that the PI3 and SLPI expressed in the endometrium and conceptus tissues play an important role in antimicrobial activity for fetal protection against potential pathogens and in blocking protease actions to allow epitheliochorial placenta formation.

• Animal Bioscience
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• v.36 no.8
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• pp.1167-1179
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• 2023

Objective: Matrix metalloproteinases (MMPs) are a family of endoproteases produced by various tissues and cells and play important roles in angiogenesis, tissue repair, immune response, and endometrial remodeling. However, the expression and function of MMPs in the pig endometrium during the estrous cycle and pregnancy have not been fully elucidated. Thus, we determined the expression, localization, and regulation of MMP2, MMP8, MMP9, MMP12, and MMP13 in the endometrium throughout the estrous cycle and at the maternal-conceptus interface during pregnancy in pigs. Methods: Endometrial tissues during the estrous cycle and pregnancy and conceptus and chorioallantoic tissues during pregnancy were obtained and the expression of MMPs was analyzed. The effects of steroid hormones and cytokines on the expression of MMPs were determined in endometrial explant cultures. Results: Expression levels of MMP12 and MMP13 changed during the estrous cycle, while expression of MMP2, MMP9, MMP12, and MMP13 changed during pregnancy. Expression of MMP2, MMP8, and MMP13 mRNAs was cell type-specific at the maternal-conceptus interface. Gelatin zymography showed that enzymatically active MMP2 was present in endometrial tissues. In endometrial explant cultures, estradiol-17β induced the expression of MMP8 and MMP12, progesterone decreased the expression of MMP12, interleukin-1β increased the expression of MMP2, MMP8, MMP9, and MMP13, and interferon-γ increased the expression of MMP2. Conclusion: These results suggest that MMPs expressed in response to steroids and cytokines play an important role in the establishment and maintenance of pregnancy by regulating endometrial remodeling and processing bioactive molecules in pigs.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.2
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• pp.159-168
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• 2010

Objective: The purpose of this study was to evaluate the correlation between the expression pattern of vascular endothelial growth factor (VEGF) in endometrium and the pathogenesis of endometriosis by investigating VEGF expression patterns and their difference between eutopic endometrium of patients with endometriosis and that of normal controls without endometriosis. Methods: Endometrial sections were obtained from 64 hysterectomy specimens from women under age of 40, who had undergone hysterectomies and had histological evidence of endometriosis, with stage 3 and 4 according to the revised American Society for Reproductive Medicine classification. As for controls, 37 sections were gained from women diagnosed as having cervical intraepithelial neoplasia (CIN) of the uterine cervix and without evidence of pelvic endometriosis or adenomyosis during their operation. The VEGF content was evaluated immunohistochemically in the eutopic endometrium from 64 patients with endometriosis and 37 normal controls. Histological semiquantitative score (H-score) was calculated and compared between study group and control group throughout the menstrual cycle. Results: There was no significant difference in the H-score of VEGF in the eutopic endometrium between patients with endometriosis and controls without endometriosis when compared according to the same phase of the cycle, although the H-score of the study group was significantly higher in the secretory phase than the proliferative phase. Conclusion: The VEGF expression in the eutopic endometrium of women with endometriosis was not different from that of women without endometriosis. This study suggests VEGF expression in eutopic endometrium is unlikely associated with the pathogenesis of endometriosis.

• Clinical and Experimental Reproductive Medicine
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• v.9 no.1_2
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• pp.55-68
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• 1982

The present investigation has been undertaken to understand the mechanism of implantation process, by demonstrating the role of ovarian steroids in connection with phosphatase activity in the differentiation of uterine endometrium for implantation. The results obtained are as followings: The differentiation of the uterine endometrial tissue was closely influenced by the ovarian steroid hormones; at first, 17${\beta}$-estradiol initiated the differentiation of the uterine luminal and glandular epithelial cells, and then progesterone induced differentiation of stromal cells, and thereby two steroids maintain decidualization of the uterine tissues. We observed that the phosphatase activities seem to be dependent upon the ovarian steroids; that is the activity showed higher level in progesterone treated group than in estradiol treated one, and the highest activity was found in the group treated with both estradiol and progesterone. Acid phosphatase showed the highest activity whereas alkaline phosphatase showed the lowest in the rat uterine endometrium during early pregnancy.

• Clinical and Experimental Reproductive Medicine
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• v.15 no.1
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• pp.53-60
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• 1988

The aim of this study was to examine the presence of ${\beta}$-endorphin in female reproductive organs. A total of 104 fresh tissue samples were obtained from normal ovary, tube, endometrium, placenta, amniotic membrane and umbilical cord, and immunostained by the method using biotin-streptoavidin amplified system. The results were as follows: 1. In reproductive age, corpus luteum only showed ${\beta}$-endorphin immunostained cells but no cells in ovaries during proliferative phase of menstrual cycle were stained. 2. Secretory endometrium revealed positive reactions in the cytoplasm of glandular epithelial cells and around the vessels, while proliferative endometrium negative reactions. 3. All the tissues of menopausal women were negative to ${\beta}$-endorphin antibody. 4. In the pregnant women, there are no ${\beta}$-endorphin containing cells in the placenta, amniotic membrane and umbilical cord regardless of gestational age.

• Journal of Embryo Transfer
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• v.27 no.4
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• pp.211-221
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• 2012

The process of embryo implantation requires physical contact and physiological communication between the conceptus trophectoderm and the maternal uterine endometrium. During the peri-implantation period in pigs, the conceptus undergoes significant morphological changes and secretes estrogens, the signal for maternal recognition of pregnancy. Estrogens secreted from the conceptus act on uterine epithelia to redirect $PGF_2{\alpha}$, luteolysin, secretion from the uterine vasculature to the uterine lumen to prevent luteolysis as well as to induce expression of endometrial genes that support implantation and conceptus development. In addition, conceptuses secrete cytokines, interferons, growth factors, and proteases, and in response to these signals, the uterine endometrium produces hormones, protease inhibitors, growth factors, transport proteins, adhesion molecules, lipid molecules, and calcium regulatory molecules. Coordinated interactions of these factors derived from the conceptus and the uterus play important roles in the process of implantation in pigs. To better understand mechanism of implantation process in pigs, this review provides information on signaling molecules at the conceptus-uterine interface during early pregnancy, including recently reported data reported.

• Clinical and Experimental Reproductive Medicine
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• v.38 no.3
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• pp.119-125
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• 2011

Implantation of an embryo occurs during the mid-secretory phase of the menstrual cycle, known as the "implantation window." During this implantation period, there are significant morphologic and functional changes in the endometrium, which is followed by decidualization. Many immune cells, such as dendritic and natural killer (NK) cells, increase in number in this period and early pregnancy. Recent works have revealed that antigen-presenting cells (APCs) and NK cells are involved in vascular remodeling of spiral arteries in the decidua and lack of APCs leads to failure of pregnancy. Paternal and fetal antigens may play a role in the induction of immune tolerance during pregnancy. A balance between effectors (i.e., innate immunity and helper T [Th] 1 and Th17 immunity) and regulators (Th2 cells, regulatory T cells, etc.) is essential for establishment and maintenance of pregnancy. The highly complicated endocrine-immune network works in decidualization of the endometrium and at the fetomaternal interface. We will discuss the role of immune cells in the implantation period and during early pregnancy.

• Clinical and Experimental Reproductive Medicine
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• v.8 no.2
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• pp.1-11
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• 1981

The quantitative analyses of the phosphatase activity in the endometrium of the rat ovariectomized on Day 2 of pregnancy was carried out in comparison with the intact one, in order to investigate the hormonal dependency of the uterus prior to the implantation, and to study the phosphatase activity in the endometrial tissues in vitro incubated in different acidity of the medium. The results obtained were as follows: 1. The activity of the total phosphatase was the highest at Day 3 of pregnancy of the intact animals irrespective of acidity of the medium. However, the ovariectomized rat showed its peak somewhat delayed. The time of the highest activity of the enzymes was matched with the time of high secretion of the ovarian hormones. 2. The activity of acid phosphatase in the endometrium was twice or four times as much high as that of neutral or alkaline phosphatase, respectively. 3. The activity of alkaline phosphatase was rather steady in Day 3 through Day 5 of the pregnancy of the rat intact or ovariectomized but with low level compared to those of other phosphatase. 4. The present re~lt indicated more important role by $Mg^{2+}$-dependent phosphatase than by $K^+$-dependent one for the preparation for decidualization.