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Decidualization of uterine stromal cells plays an important role in the establishment of normal pregnancy. Previous studies have demonstrated that Acyl-CoA binding protein (Acbp) is critical to cellular proliferation, differentiation, mitochondrial functions, and autophagy. The characterization and physiological function of Acbp during decidualization remain largely unknown. In the present study, we conducted the expression profile of Acbp in the endometrium of early pregnant mice. With the occurrence of decidualization, the expression of Acbp gradually increased. Similarly, Acbp expression was also strongly expressed in decidualized cells following artificial decidualization, both in vivo and in vitro. We applied the mice pseudopregnancy model to reveal that the expression of Acbp in the endometrium of early pregnant mice was not induced by embryonic signaling. Moreover, P4 significantly upregulated the expression of Acbp, whereas E2 appeared to have no regulating effect on Acbp expression in uterine stromal cells. Concurrently, we found that interfering with Acbp attenuated decidualization, and that might due to mitochondrial dysfunctions and the inhibition of fatty acid oxidation. The level of autophagy was increased after knocking down Acbp. During induced decidualization, the expression of ACBP was decreased with the treatment of rapamycin (an autophagy inducer), while increased with the addition of Chloroquine (an autophagy inhibitor). Our work suggests that Acbp plays an essential role in the proliferation and differentiation of stromal cells during decidualization through regulating mitochondrial functions, fatty acid oxidation, and autophagy.

Trophoblast development is a crucial event in placentation and pregnancy complications but its underlying mechanisms remain unclear. Thus, we aimed at investigating the role of DiOThe placental villous expression of DiODiODuring placentation, DiO

Maternal exposure to endocrine-disrupting chemicals (EDCs) is associated with long-term hormone-dependent effects that are sometimes not revealed until maturity, middle age, or adulthood. The aim of this study was to conduct descriptive reviews on animal experimental and human epidemiological evidence of the adverse health effects of in utero and lactational exposure to selected EDCs on the first generation and subsequent generation of the exposed offspring. PubMed, Web of Science, and Toxline databases were searched for relevant human and experimental animal studies on 29 October 29 2018. Search results were screened for relevance, and studies that met the inclusion criteria were evaluated and qualitative data extracted for analysis. The search yielded 73 relevant human and 113 animal studies. Results from studies show that in utero and lactational exposure to EDCs is associated with impairment of reproductive, immunologic, metabolic, neurobehavioral, and growth physiology of the exposed offspring up to the fourth generation without additional exposure. Little convergence is seen between animal experiments and human studies in terms of the reported adverse health effects which might be associated with methodologic challenges across the studies. Based on the available animal and human evidence, in utero and lactational exposure to EDCs is detrimental to the offspring. However, more human studies are necessary to clarify the toxicological and pathophysiological mechanisms underlying these effects.

It is well known that maternal folate deficiency results in adverse pregnancy outcomes. In addition to aspects in embryonic development, maternal uterine receptivity and the decidualization of stromal cells is also very important for a successful pregnancy. In this study, we focused on endometrium decidualization and investigated whether apoptosis, which is essential for decidualization, was impaired. Flow cytometry and TUNEL detection revealed that apoptosis of mouse endometrium decidual cells was suppressed in the dietary folate-deficient group on Days 7 and 8 of pregnancy (Day 1 = vaginal plug) when decidua regression is initiated. The endometrium decidual tissue of the folate deficiency group expressed less Bax compared to the normal diet group while they had nearly equal expression of Bcl2 protein. Further examination revealed that the mitochondrial transmembrane potential (ΔΨm) decreased, and the fluorescence of diffuse cytoplasmic cytochrome c protein was detected using laser confocal microscopy in normal decidual cells. However, no corresponding changes were observed in the folate-deficient group. Western blotting analyses confirmed that more cytochrome c was released from mitochondria in normal decidual cells. Taken together, these results demonstrated that folate deficiency could inhibit apoptosis of decidual cells via the mitochondrial apoptosis pathway, thereby restraining decidualization of the endometrium and further impairing pregnancy.

To assess the relationship between folate biomarkers levels and IGF2 imprinting status among second trimester pregnant Chinese women.Three hundred women in their second trimester were screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for analysis of IGF2 imprinting status. Statistical differences of folate biomarkers levels were calculated in the groups with different imprinting status.Of the 300 women analyzed, 133 (44.33%) cases were homozygous allele with A, 3 (1.00%) cases were homozygous allele with G, while 164 (54.67%) cases were heterozygous with A and G, qualifying them for analysis of loss of imprinting (LOI). Among the 164 cases undergoing LOI analysis, 44 (26.83%) were IGF2 LOI cases, while 120 (73.17%) were IGF2 retention of imprinting (ROI) ones. The mean level of serum folate, vitamin B12 and tHcy was 28.46 +/- 10.74 ng/mL, 380.20 +/- 206.13 pg/mL, 14.24 +/- 6.34 micromol/L among women with IGF2 ROI, and 30.89 +/- 9.97 ng/mL, 394.28 +/- 195.92 pg/ mL, and 13.12 +/- 6.23 micromol/L among women with IGF2 LOI, respectively.No significant difference of folate biomarkers levels was observed between IGF2 ROI and IGF2 LOI groups.

To investigate the expression of human spindle mitosis arrest deficiency gene (hsMAD2) in spontaneous abortion embryos and the relationship between low expression of hsMAD2 and numerical chromosomal aberration. METHODS Spontaneous abortion embryo tissues were collected, including 23 cases of once spontaneous abortion tissue and 10 cases of twice or more spontaneous abortion tissue and induced abortion embryos (35 cases) from the Department of Gynaecology and Obstetrics of the Affiliated Hospitals of Chongqing University of Medical Science during the period of March 2006 to March 2007. FQ-PCR and western blot were used to evaluate the endogenous expression level of hsMAD2 mRNA and hsMAD2 protein; primary culturing of cells from the induced abortion embryos was conducted and 5 embryonic cells were selected by chromosomes karyotype analysis. Recombinant shRNA plasmids targeting hsMAD2 gene were constructed to inhibit the expression of endogenous hsMAD2 genes in embryonic cells which have normal karyotypes; the groups were defined as the first experimental group (transfected with pshRNA-hsMAD2-1) , the second experimental group (transfected with pshRNA-hsMAD2-2), the third experimental group (transfected with pshRNA-hsMAD2-3), the first control group (transfected with nothing), the second control group (transfected with pTZU6 + 1) and the independent group (transfected with pshRNA-N1). Interference efficiency was demonstrated by FQ-PCR and western blot; cell proliferation was measured by methyl thiazolyl tetrazolium (MTT) assay; cell-cycle was assessed by flow cytometry (FCM); the chromosome numbers were calculated to analyze the variation of chromosomes.(1) The mRNA levels of hsMAD2 in the once spontaneous abortion tissue, twice or more spontaneous abortion tissue and induced abortion tissue were 0.00879 +/- 0.00035, 0.00901 +/- 0.00033 and 0.00941 +/- 0.00026 respectively, and there was no significant difference (P0.05) compared with each other; however, the protein levels of hsMAD2 in three groups were 0.2791 +/- 0.0311, 0.0431 +/- 0.0020 and 0.5790 +/- 0.0331 respectively, and there were significant differences (P0.05) compared with each other. (2) Recombinant shRNA plasmids could significantly and specifically inhibit hsMAD2 gene expression in embryonic cells. Compared with the first control group (4%) and the second control group (3%), the recombinant shRNA could inhibit embryonic cell proliferation to 54% at 48 h after transfection (P0.05); compared with the first control group (8.2%) and the second control group (8.0%), the ratios of G2/M phase cells in the experimental group (17.9%)was significantly increased (P0.05); compared with the first control group (4.8%), the ratios of abnormal chromosomes in the experimental group was increased to 30.0% (P0.05).Down-expression of hsMAD2 gene may be one of the mechanisms inducing numerical chromosome aberration, abnormal embryo development and the occurrence of spontaneous abortion.

The expression and distribution of the imprinted paternally expressed gene 10 (PEG10) in decidual tissues of 36 patients with inevitable abortion and 36 normal pregnant (NP) women were examined by RT-PCR, immunohistochemistry, in situ hybridization and Western blot. Decidual PEG10 mRNA expression was significantly lower in the patients than that in the NP group by RT-PCR (P0.05). The characteristic PEG10 expression was confirmed by in situ hybridization. As shown by Western blot and immunohistochemistry, PEG10 protein expression was consistent with the mRNA expression pattern. The results showed that maintaining sufficient levels of PEG10 may be important during early pregnancy. Lower levels of PEG10 might be one of reasons that underlie inevitable abortion.

To survey the role of hepatocyte growth factor activator inhibitor type 1 (HAI-1) in early embryo development, we study the HA-1 gene expressing in villous tissue after embryo implantation.Fifty villous tissue samples from pregnant 6 w to 10 w were divided into five groups and each group included ten samples. The HAI-1 gene and protein expressing in the villous tissue were detected by RT-PCR and immunohistochemistry.The expression of HAI-1 had a gradual increase with the pregnancy weeks added. The HAl-1 gene expression was very low at pregnant 6 w(A(260/280) 0.3142), From pregnant 7 w to 9 w, the expression was increased gradually (A(260/280) 0.3476 in 7 w and 0.3910 in 8 w) and reached the pinnacle in 9 w (A(260/280) 0.4876). And then the pinnacle value lasted until 10 w (A(260/280) 0.4909). The proportion of HAI-1 mRNA/beta-actin mRNA between 9 w and 10 w was not significantly different (Por = 0.05). But among the other 3 groups, the proportion was significantly different (P0.01). The proportion of 9 w and 10 w was significantly different from the other 3 groups (P0.01). The results of HAI-1 protein expression showed the similar conclusion by immunohistochemical analysis.The HAI-1 gene may play an important role in early embryo development in human.

The nm23 gene family was involved in cellular multiphysiopathological processes including differentiation, development, apoptosis and cancer promotion, progression or metastasis. Some data indicate that nm23 plays an important role in regulating reproductive processes. In the present study, we analyzed the proteome of the implantation sites and the peri-implantation sites in NIH. mice on Day 5 of gestation by using two-Dimensional gel electrophoresis (2-D PAGE), while the virgin mice as the control. A protein spot with pI 7.1, Mr 18 kDa showed up-regulated expression in endometrium during the blastocysts adhesiveness. Using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS), this protein was identified as nm23-M2/NDPK B. The nm23-M2 expression in mice endometrium was shown progressive increase on Day 5 of gestation by RT-PCR, which was consistent with the result obtained by immunohistochemistry. These findings suggest that nm23-M2/NDPK B was involved in the process of blastocyst implantation.

The nm23 gene was originally identified as a metastasis suppressor gene by differential hybridization of non-metastatic and metastatic clones of murine K-1735 melanoma cell lines. Subsequently, other highly homologous genes were characterized and shown to code for nucleoside diphosphate kinase (NDPK) isotypes. These enzymes have been evidenced in a wide variety of organisms. In human, up to eight distinct but highly related genes have been discovered. The nm23-H1 and nm23-H2 gene products share 88% identity and are about 95% and 98% identical to the murine nm23-M1 and nm23-M2 proteins respectively. A number of data indicate that nm23 family, initially documented as metastasis suppressors in some cancer types, are involved in the control of normal development, differentiation and apoptosis. The trophoblast cells of blastocyst and of the normal first-trimester placenta share some phenotypic similarities with malignant cells, such as rapid proliferation and ability to invade neighbouring tissues, including basement membrane, during the process of implantation and placental development, but do not have the ability for unlimited growth or metastasis, as few trophoblast cells can be identified in the deciduas, and trophoblasts rarely penetrate the maternal blood vessels. Although some data indicate that nm23 family play an important role in regulation of reproductive processes, little is know about its actual mechanism. In our studies, we performed RT-PCR, Western blot and immunohistochemical analyses of nm23-M1/NDPK A expression during the blastocyst adhesiveness in the mouse endometrium. The nm23-M1 mRNA expression was shown progressive increase in D5 mice endometrium by RT-PCR, which was consistent with the result obtained by Western blot and immunohistochemistry. It is suggested that nm23-M1/NDPK A was involved in the process of blastocyst implantation.