The onset of pregnancy is marked by the formation of a zygote, while the culmination of gestation is manifested by the delivery of a fetus. Meanwhile, a successful pregnancy entails a meticulously coordinated sequence of events from embryo implantation to sustained decidualization of the uterus to placental development and childbirth. The decidual reaction, a pivotal process occurring within the endometrium during pregnancy, is finely regulated by sex steroids and cytokines. Notably, fibroblast growth factors (FGFs), particularly FGF2, play a critical role in this physiological cascade. Dysregulated FGF expression may trigger inadequate decidualization, precipitating a spectrum of adverse pregnancy outcomes, including preeclampsia, recurrent implantation failure, and miscarriage. Furthermore, the human decidua, distinct from most mammalian species and similar to great apes, undergoes regular cycles of formation and shedding, independent of the presence of the embryo in the endometrium. This process is also tightly controlled by various FGFs. In this review, we comprehensively compare diverse research decidualization models, delineate the trend of endometrial FGFs during the menstrual cycle, and provide a synopsis of endometrial diseases triggered by FGF dysregulation.
Humans ; Female ; Pregnancy ; Decidua/physiology* ; Animals ; Endometrium/physiology* ; Fibroblast Growth Factors/metabolism* ; Embryo Implantation ; Menstrual Cycle/physiology*

OBJECTIVETo investigate the biological features of human decidua basalis-derived mesenchymal stem cells (PDB-MSCs) in vitro and identify their capacity of multilineage differentiation.

METHODSPDB-MSCs were harvested from the decidua basalis of term placental by enzymatic digestion and density gradient centrifugation, and the growth characteristics and morphological changes of the MSCs were observed by inverted microscope. The proliferative ability of the cells was assessed by Cell Counting Kit-8. The cell cycle and expressions of the surface markers (CD29, CD44, CD73, CD90, CD34, CD45, and CD14) of the MSCs were identified by flow cytometry. Multilineage differentiation capacity of the cells was tested by inducing their differentiation toward osteoblasts, adipocytes and chondroblasts in vitro.

RESULTSMSCs isolated from human decidua basalis of term placental exhibited a morphology similar to that of bone marrow-derived MSCs, and grew into colonies in in vitro culture, where the cells proliferated rapidly after passage with a cell doubling time of 2.21∓0.21 days. More than 70% of the cells stayed in the resting stage (G(0)/G(1)) and showed positivity for CD29, CD44, CD73 and CD90, but not for CD14, CD34 or CD45. After induction, the cells showed positive results of alizarin red staining, oil red O staining and Alcian blue staining.

CONCLUSIONHuman decidua basalis contains a rich source of MSCs, which can be easily isolated and cultured without affecting their capacity of multilineage differentiation. The PDB-MSCs may have the potential as a novel source of stem cells.

Cell Differentiation ; physiology ; Cell Separation ; Cells, Cultured ; Decidua ; cytology ; Female ; Humans ; Mesenchymal Stromal Cells ; cytology ; Multipotent Stem Cells ; cytology ; Placenta ; cytology ; Pregnancy

BACKGROUNDBAFF, the B cell activation factor, is a member of the tumor necrosis factor (TNF) ligand family that binds to BCMA, TACI, and BAFF-R. Previous studies have shown that members of the TNF family are detected in human placental trophoblast cells, but the expression patterns of BAFF involved in human decidua and the differential expression of BAFF between normal pregnancy and miscarriage are still incompletely documented or unknown. This study was designed to investigate the expression of BAFF and BAFF-R in the trophoblast and decidua of normal early pregnant women and recurrent spontaneous abortion (RSA) patients.

METHODSForty-five patients with RSA and 45 normal pregnant women were included in this study. By reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemical experiments, we explored the expression of BAFF and BAFF-R in the maternal-fetal interface of normal early pregnant women and RSA patients.

RESULTSAnalysis by RT-PCR and Western blotting revealed that BAFF was detected in both trophoblast and decidua of all the samples, and the expression level was higher in the tissues of normal early pregnant women (P<0.05) than that of recurrent spontaneous abortion patients under the same gestational weeks. Messages for BAFF-R were absent. Immunohistochemical experiments showed that expression of BAFF was cell-specific which was localized to villous cytotrophoblast and syncytiotrophoblast cells in trophoblast and to stromal cells in decidua. Whereas BAFF was prominent on the trophoblast and decidua of normal early pregnant women, it was decreased in the tissues of RSA patients.

CONCLUSIONSBAFF might steer maternal leukocytes away from a harmful immune response and toward a favorable one and play a potentially vital role for successful pregnancy.

Abortion, Habitual ; metabolism ; B-Cell Activating Factor ; analysis ; genetics ; physiology ; Decidua ; chemistry ; metabolism ; Female ; Humans ; Immunohistochemistry ; Interleukin-10 ; genetics ; Pregnancy ; RNA, Messenger ; analysis ; Th1 Cells ; immunology ; Th2 Cells ; immunology ; Trophoblasts ; chemistry ; metabolism

OBJECTIVETo develop a convenient method for isolation and purification of human extravillous cytotrophoblasts (EVCTs) and decidual stromal cells (DSCs) and establish a co-culture system.

METHODSThe DSCs were digested with trypsin and purified by Percoll gradient. The EVCTs were digested with trypsin and purified by BSA gradient. Immunohischemistry and immunofluorescent study are performed to characterize these isolated cells. The EVCTs and DSCs were placed in Matrigel-coated Transwell upper and lower chamber, respectively, to study the invasive ability of the EVCTs.

RESULTSImmunohischemistry revealed that the purity of EVCTs and DSC exceeded 95%. Cultured EVCTs retained their capacity to invade Matrigel-coated Transwell filters with the invasion index of 3.22-/+0.04.

CONCLUSIONThis co-culture model established by isolating highly purified EVCTs and DSCs in vitro can be useful for studying the trophoblast invasion mechanisms.

Cell Communication ; physiology ; Cells, Cultured ; Chorion ; cytology ; Coculture Techniques ; Decidua ; cytology ; Female ; Humans ; Models, Biological ; Stromal Cells ; cytology ; Trophoblasts ; cytology ; physiology

To investigate the expression of the subunit p65 of NF-kappaB and inhibitor kappa B alpha (IkappaBalpha) in mouse uterus during peri-implantation, thereby investigating whether transient activation of nuclear factor-kappaB (NF-kappaB) takes place during embryo implantation in mice. Immunohistochemical technique was used to examine the expression and localization of p65 in endometrium or deciduas, and Western blot analysis was employed to detect the levels of IkappaBalpha protein in mouse endometrium or deciduas. P65 protein was detected in stromal cells, epithelial cells of endometrium as well as in myometrium. Staining was predominately seen in the cytoplasm of the cells. Staining intensity for p65 was stronger in the epithelial compartment than the stromal compartment and myometrium. Staining intensity increased slightly during pregnancy, and it reached a high level on pregnancy day 5 and day 8. In contrast to p65, the level of IkappaBalpha protein was lowest on pregnancy day 5 in all groups. Our results suggested that NF-kappaB may regulate embryo implantation by its transient activation in mice.
Animals ; Decidua ; metabolism ; Embryo Implantation ; physiology ; Endometrium ; metabolism ; Female ; I-kappa B Proteins ; biosynthesis ; Mice ; NF-KappaB Inhibitor alpha ; NF-kappa B ; biosynthesis ; Pregnancy ; Time Factors ; Uterus ; metabolism ; physiology

To investigate the expression of the subunit p65 of NF-kappaB and inhibitor kappa B alpha (IkappaBalpha) in mouse uterus during peri-implantation, thereby investigating whether transient activation of nuclear factor-kappaB (NF-kappaB) takes place during embryo implantation in mice. Immunohistochemical technique was used to examine the expression and localization of p65 in endometrium or deciduas, and Western blot analysis was employed to detect the levels of IkappaBalpha protein in mouse endometrium or deciduas. P65 protein was detected in stromal cells, epithelial cells of endometrium as well as in myometrium. Staining was predominately seen in the cytoplasm of the cells. Staining intensity for p65 was stronger in the epithelial compartment than the stromal compartment and myometrium. Staining intensity increased slightly during pregnancy, and it reached a high level on pregnancy day 5 and day 8. In contrast to p65, the level of IkappaBalpha protein was lowest on pregnancy day 5 in all groups. Our results suggested that NF-kappaB may regulate embryo implantation by its transient activation in mice.
Decidua/metabolism ; Embryo Implantation/*physiology ; Endometrium/metabolism ; I-kappa B Proteins/*biosynthesis ; NF-kappa B/*biosynthesis ; Time Factors ; Uterus/*metabolism ; Uterus/physiology

The enzyme complex 3b-hydroxysteroid dehydrogenase/delta(5)-delta(4)-isomerase (3beta-HSD) is involved in the biosynthesis of all classes of active steroids. The expression of 3beta-HSD in human uterine endometrium during the menstrual cycle and decidua was examined in an effort to understand its role during ova implantation. 3beta-HSD was weakly expressed in the glandular epithelium of the proliferative phase and moderately expressed in the glandular epithelium of secretory phase of the endometrium. In the decidua of the ectopic pregnancy, 3beta-HSD was strongly expressed. The human uterine endometrial 3beta-HSD was identified as being the same type as the placental 3beta-HSD by RT-PCR and sequence analysis. In addition to the expression of 3beta-HSD, P450scc was expressed in the decidua of the ectopic pregnancy. These results suggest that pregnenolone might be synthesized from cholesterol by P450scc de novo and then, it is converted to progesterone by 3beta-HSD in the uterine endometrium. The data implies that the endometrial 3beta-HSD can use not only the out-coming pregnenolone from the adrenal gland but also the self- made pregnenolone to produce progesterone. The de novo synthesis of progesterone in the endometrium might be a crucial factor for implantation and maintenance of pregnancy.
Cholesterol/chemistry ; Cholesterol Side-Chain Cleavage Enzyme/*biosynthesis/genetics ; Decidua/enzymology ; Endometrium/*enzymology ; Female ; Gene Expression/physiology ; Human ; Menstrual Cycle/physiology ; Multienzyme Complexes/*biosynthesis/genetics ; Placenta/enzymology ; Pregnancy ; Pregnenolone/biosynthesis ; Progesterone/biosynthesis ; Progesterone Reductase/*biosynthesis/genetics ; Steroid Isomerases/*biosynthesis/genetics