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In mammals, the establishment of pregnancy is dependent upon coordinated biochemical signaling and physical interactions between the developing conceptus and uterine endometrium. These essential forms of communication between the conceptus and its maternal environment result in continued production of progesterone from the corpus luteum (CL) and the initiation of implantation/placentation. During the peri-implantation period, conceptuses in ruminant ungulates secrete interferon-tau (IFNT), which acts on uterine endometrium and attenuates endometrial production of the luteolysin, prostaglandin F2α, resulting in the maintenance of CL function. Expression of the ovine IFNT (olFNT) genes is restricted to the mononuclear cells of the trophoblast and the protein is produced for only a relatively short and discrete window of time during early pregnancy. This review deals with identification, characterization and regulation of IFNT gene transcription, and uterine responses associated with pregnancy establishment in ruminants.
Synchronous embryonic development and uterine differentiation is crucial to successful implantation and to pregnancy outcome; reciprocal interactions between the implantation-competent blastocyst and receptive uterus are necessary for successful implantation. Implantation involves the interplay of numerous signaling molecules, and the process is complicated and varies across species. Therefore, investigations into embryo and uterus crosstalk, including comparative research among species are necessary to improve reproductive biomedicine and animal husbandry. We herein focus on species-specific morphological changes, hormonal control, and molecular interactions that occur in the uterus and embryo during implantation in laboratory animals.
Recent advances in assisted reproductive technologies (ART) have resulted in higher fertilization rates for infertile couples. However, successful pregnancy is prevented by failure of the embryo to implant in the endometrium. Human embryo implantation involves apposition and adhesion, followed by penetration through the endometrial epithelial layer and invasion of the embryo into the endometrial stroma. Human implantation is a multi-step event requiring the orchestrated regulation of endometrial cells, involving cell proliferation, differentiation, motility, and adhesion. Reversible histone acetylation affects functional protein expression by regulating gene transcription. Histone deacetylase inhibitors (HDACIs) can induce expression of specific proteins, thereby affecting cell function. At present, HDACIs are used in anticancer therapy to induce cancer cell apoptosis. In this review, we discuss the potential of HDACIs for supportive therapy of infertility caused by endometrial dysfunction, and introduce recent reports that HDACIs target and affect various cell functions.
Attachment to endometrial epithelium is an essential process for human embryos. Although it is widely accepted that this process is largely regulated by the endocrine system, the precise molecular mechanism(s) remains unclear. Recent evidence suggests that immune cells actively contribute to the establishment of embryo implantation. In accordance with this, we found that peripheral blood immune cells positively affect the differentiation of maternal endometrium to facilitate embryo implantation during early pregnancy. From these findings, we propose a novel concept that circulating immune cells are important regulators of embryo implantation. Lately, implantation failure in patients treated with in vitro fertilization and embryo transfer has received increasing attention. Based on our hypothesis, we have successfully developed a new therapy for implantation failure using autologous peripheral blood immune cells. These findings suggest that supportive mechanisms via the immune system facilitate embryo implantation and will be useful in the field of assisted reproductive technology.
Dramatic advances in assisted reproductive technologies have greatly improved the pregnancy rate for infertile couples. Recently, however, the recent pregnancy rates and live-birth rates have not significantly increased, mainly because there are very few effective treatments available for implantation failure and subsequent early pregnancy loss. Successful implantation requires good embryo quality, appropriately timed and arranged endometrial receptivity, and the efficient crosstalk between the embryo and the receptive endometrium. It is thought that impairment of any one of these factors or biological processes may result in implantation failure. In this review article, I have focused on endometrial dysfunction as a cause of implantation failure, and discuss its possible etiologies and therapeutic strategies.
The aim of this study was to clarify the mechanism underlying the low implantation rate in patients with thin endometrium. Endometrial thickness during postovulation days 5–7 (mid-luteal phase) during a total of 1,035 natural cycles in 205 patients was analyzed retrospectively. We designated patients with endometrial thicknesses ≤ 6 mm as the thin group (n = 12) and those with endometrial thicknesses ≥ 7 mm as the normal group (n = 193), based on the markedly lower pregnancy rate in the thin group (thin: 8.3% vs. normal: 51.3%). Levels of steroid receptor, transforming growth factor α (TGFα) and oxidative stress were compared between the two groups. Oxidative stress was higher in the stroma of thin endometrium. In addition, expression of progesterone and estrogen receptors was higher, and TGF α expression was significantly lower in thin endometrium. Altered regulation of oxidative stress and levels of steroid receptors and TGF α appear to underlie the low implantation rate seen in patients with thin endometrium.
The effect of cysteamine added to maturation medium on nuclear maturation, ATP content and glutathione (GSH) content of porcine oocytes was investigated. The nuclear maturation up to the metaphase stage of second meiotic division (the M-II stage) of cumulus cell-enclosed oocytes (COs) matured with various concentrations (0, 15, 45, 150, and 450 µM) of cysteamine was observed. The maturation rate of the 150 µM group was significantly higher (P < 0.05) than that of the control (0 µM) group. Although the ATP content of oocytes derived from COs matured with 150 µM cysteamine was the same as that of the immature group, the ATP content of COs matured without cysteamine was significantly higher (P < 0.05) than that of the immature group. Conversely, the GSH content of oocytes derived from COs matured with 150 µM cysteamine was significantly higher (P < 0.05) than that of the immature group. However, the content of the group matured without cysteamine was not significantly different from that of the immature group. These results indicate that cysteamine added to maturation medium may stimulate the nuclear maturation of porcine oocytes by increasing the GSH content without enhancing the oocyte ATP content.
In this study, we used SrCl2 treatment to activate mouse oocytes. The objectives of this study were to compare the development of parthenogenic and fertilized mouse embryos, and the effect of insulin-like growth factor II (IGF-II) on their development to blastocysts; glucose and methionine metabolism were also examined. Compared to normal fertilized embryos, parthenogenically developed embryos exhibited delayed development, reduced total cell number, and reduced trophectoderm cell (TC) and inner cell mass (ICM) cell numbers of blastocysts. Supplementation of IGF-II to the culture medium enhanced parthenogenic embryo development, cell number, and TC and ICM cell numbers but not to the same level as that of normal fertilized embryos (P < 0.05). Incorporation and oxidation of glucose and protein synthesis from methionine were lower in parthenogenic blastocysts than in fertilized blastocysts (P < 0.05).
The effects of β-hydroxybutyrate (BHB) added to a modified NCSU37 medium during in vitro maturation (IVM) on nuclear maturation, and ATP and glutathione (GSH) contents of porcine oocytes were investigated. Nuclear maturation up to the metaphase stage of the second meiotic division (the M-II stage) of cumulus cell-enclosed oocytes (COs) matured with various concentrations (0.0, 2.3, 3.1, 3.9 and 4.7 mM) of BHB was observed. The nuclear maturation rate of the oocytes of the 3.1 mM group was significantly higher (P < 0.05) than that of the control (0.0 mM) group. Both the ATP and GSH contents of the oocytes matured with or without 3.1 mM BHB and removed from cumulus cells after IVM were not significantly different. These results indicate that 3.1 mM BHB added to the maturation medium may stimulate the nuclear maturation of porcine oocytes without changing their ATP and GSH contents.