Human Platelet-Rich Plasma Facilitates Angiogenesis to Restore Impaired Uterine Environments with Asherman's Syndrome for Embryo Implantation and Following Pregnancy in Mice.

Asherman's syndrome (AS) is caused by intrauterine adhesions and inactive endometrium from repeated curettage of the uterine endometrium. AS is a major cause of recurrent implantation failure and miscarriage and is very difficult to treat because of the poor recovery of endometrial basal cells. Platelet-rich plasma (PRP) has abundant growth factors that may induce angiogenesis and cell proliferation.

Voltage Dependent N Type Calcium Channel in Mouse Egg Fertilization.

Repetitive changes in the intracellular calcium concentration ([Ca]i) triggers egg activation, including cortical granule exocytosis, resumption of second meiosis, block to polyspermy, and initiating embryonic development. [Ca]i oscillations that continue for several hours, are required for the early events of egg activation and possibly connected to further development to the blastocyst stage. The sources of Ca ion elevation during [Ca]i oscillations are Ca release from endoplasmic reticulum through inositol 1,4,5 tri-phosphate receptor and Ca ion influx through Ca channel on the plasma membrane.

Recovery of ovarian function by human embryonic stem cell-derived mesenchymal stem cells in cisplatin-induced premature ovarian failure in mice.

Background: Clinical use of mesenchymal stem cells (MSCs) requires a uniform cell population, and their harvesting is invasive and produces a limited number of cells. Human embryonic stem cell-derived MSCs (hESC-MSCs) can differentiate into three germ layers and possess immunosuppressive effects in vitro. Anticancer treatment is a well-known risk factor for premature ovarian failure (POF).

Hyperandrogenic Milieu Dysregulates the Expression of Insulin Signaling Factors and Glucose Transporters in the Endometrium of Patients With Polycystic Ovary Syndrome.

Purpose: Subfertility associated with polycystic ovary syndrome (PCOS) mainly originates from oligoovulation/anovulation. Although insulin resistance and androgen excess are known to cause PCOS-associated implantation failure, the consequences of PCOS on endometrial homeostasis and pathophysiology have not been comprehensively understood. In this study, we examined whether the pathophysiologic milieu of PCOS intrinsically affects expression profiles of genes related to insulin signaling and facilitative glucose transporters (GLUTs) in the human endometrium and/or during in vitro decidualization.

Hyperandrogenic Milieu Dysregulates the Expression of Insulin Signaling Factors and Glucose Transporters in the Endometrium of Patients With Polycystic Ovary Syndrome.

Purpose:: Subfertility associated with polycystic ovary syndrome (PCOS) mainly originates from oligoovulation/anovulation. Although insulin resistance and androgen excess are known to cause PCOS-associated implantation failure, the consequences of PCOS on endometrial homeostasis and pathophysiology have not been comprehensively understood. In this study, we examined whether the pathophysiologic milieu of PCOS intrinsically affects expression profiles of genes related to insulin signaling and facilitative glucose transporters (GLUTs) in the human endometrium and/or during in vitro decidualization.

PLGA nanoparticles with multiple modes are a biologically safe nanocarrier for mammalian development and their offspring.

Nano-sized particles (NPs) of various materials have been extensively used as therapeutic and diagnostic agents, drug delivery systems, and biomedical devices. However, the biological impacts of NP exposure during early embryogenesis on following development and next generations have not been investigated. Here, we demonstrated that polylactic-co-glycolic acid (PLGA)-NPs were not toxic and did not perturb development of preimplantation mouse embryos in vitro.

Estrogen induces EGR1 to fine-tune its actions on uterine epithelium by controlling PR signaling for successful embryo implantation.

The harmonized actions of ovarian E and progesterone (P) regulate the proliferation and differentiation of uterine cells in a spatiotemporal manner. Imbalances between these hormones often lead to infertility and gynecologic diseases. Whereas numerous factors that are involved in P signaling have been identified, few local factors that mediate E actions in the uterus have been revealed.

Estrogen-induced transcription factor EGR1 regulates c-Kit transcription in the mouse uterus to maintain uterine receptivity for embryo implantation.

Early growth response 1 (Egr1) is a key transcription factor that mediates the action of estrogen (E) to establish uterine receptivity for embryo implantation. However, few direct target genes of EGR1 have been identified in the uterus. Here, we demonstrated that E induced EGR1-regulated transcription of c-Kit, which plays a crucial role in cell fate decisions.

Association of human leukocyte antigen with postherpetic neuralgia in Koreans.

Postherpetic neuralgia (PHN), the most frequent complication of varicella-zoster virus reactivation, is characterized by pain that persists for more than 3 months, often for years after healing of zoster rash. A few studies revealing the association of human leukocyte antigen (HLA) with PHN have been reported, but only in the Japanese. The aim of this study was to investigate the primary HLA locus associated with PHN susceptibility in Koreans.

Integrative Analyses of Uterine Transcriptome and MicroRNAome Reveal Compromised LIF-STAT3 Signaling and Progesterone Response in the Endometrium of Patients with Recurrent/Repeated Implantation Failure (RIF).

Intimate two-way interactions between the implantation-competent blastocyst and receptive uterus are prerequisite for successful embryo implantation. In humans, recurrent/repeated implantation failure (RIF) may occur due to altered uterine receptivity with aberrant gene expression in the endometrium as well as genetic defects in embryos. Several studies have been performed to understand dynamic changes of uterine transcriptome during menstrual cycles in humans.

Deficiency in DGCR8-dependent canonical microRNAs causes infertility due to multiple abnormalities during uterine development in mice.

DGCR8 is an RNA-binding protein that interacts with DROSHA to produce pre-microRNA in the nucleus, while DICER generates not only mature microRNA, but also endogenous small interfering RNAs in the cytoplasm. Here, we produced Dgcr8 conditional knock-out mice using progesterone receptor (PR)-Cre (Dgcr8(d/d)) and demonstrated that canonical microRNAs dependent on the DROSHA-DGCR8 complex are required for uterine development as well as female fertility in mice. Adult Dgcr8(d/d) females neither underwent regular reproductive cycles nor produced pups, whereas administration of exogenous gonadotropins induced normal ovulation in these mice.

Egr1 is rapidly and transiently induced by estrogen and bisphenol A via activation of nuclear estrogen receptor-dependent ERK1/2 pathway in the uterus.

Coordinate actions of ovarian estrogen (E2) and progesterone (P4) via their own receptors are critical for establishing uterine receptivity for embryo implantation in the uterus. E2 regulates expression of an array of genes to mediate its major actions on heterogeneous uterine cell types. Here we have investigated regulatory mechanism(s) of E2 and bisphenol A (BPA), an endocrine disruptor with potent estrogenic activity on expression of early growth response 1 (Egr1), a zinc finger transcription factor that regulates cell growth, differentiation and apoptosis in the uterus.

A one step multiplex PCR assay for rapid screening of East Asian mtDNA haplogroups on forensic samples.

The mitochondrial DNA (mtDNA) haplogroup typing has become an essential tool to study human evolutionary history and to infer the matrilineal bio-geographic ancestry. In forensic field, the screening of mtDNA haplogroups by genotyping of mtDNA single nucleotide polymorphisms (SNPs) can help guarantee the quality of mtDNA sequence data as well as can reduce the need to sequence samples that do not match. Here, a multiplex mutagenically separated (MS) polymerase chain reaction (PCR) system was developed for simultaneous rapid detection of 14 coding region SNPs and one deletion motif representing common mtDNA haplogroups of East Asia.

Activation of peroxisome proliferators-activated receptor δ (PPARδ) promotes blastocyst hatching in mice.

Prostaglandins participate in a variety of female reproductive processes, including ovulation, fertilization, embryo implantation and parturition. In particular, maternal prostacyclin (PGI(2)) is critical for embryo implantation and the action of PGI(2) is not mediated via its G-protein-coupled membrane receptor, IP, but its nuclear receptor, peroxisome-proliferator-activated receptor δ (PPARδ). Recently, several studies have shown that PGI(2) enhances blastocyst development and/or hatching rate in vitro, and subsequently implantation and live birth rates in mice.

Preeclampsia leads to dysregulation of various signaling pathways in placenta.

Objectives: To compare gene expression profiles of placentas from preeclamptic and normal pregnancies.

Study Design: We performed microarray experiments to analyze genome-wide expression profiling for 10 placentas from pregnant women with preeclampsia and 10 placentas from women who experienced noncomplicated pregnancies (CON), and to identify dysregulated signaling pathways as well as genes in preeclampsia. RT-PCR, real-time RT-PCR and/or immunofluorescence analyses were performed to validate the data obtained from microarray experiments.

Forensic and genetic characterization of mtDNA from Pathans of Pakistan.

Complete mitochondrial control region data were generated for 230 unrelated Pathans from North West Frontier Province and Federally Administered Tribal Areas of Pakistan. To confirm data quality and to explore the genetic structure of Pathans, mitochondrial DNA haplogroup affiliation was determined by shared haplogroup-specific polymorphisms in the control region and by the analysis of diagnostic coding region single-nucleotide polymorphisms using a multiplex system for the assignment of eight haplogroups: M, N1'5, W, R, R0, T, J, and U. Sequence comparison revealed that 193 haplotypes were defined by 215 variable sites when major insertions were ignored at nucleotide positions 16193, 309, and 573.

[Allelic and haplotypic diversity of HLA-A, -B, -C, and -DRB1 genes in Koreans defined by high-resolution DNA typing].

Background: In this study, we used high-resolution DNA typing to investigate the distribution of HLA alleles and haplotypes in Koreans.

Methods: HLA-A, -B, -C, and -DRB1 alleles were genotyped at the allelic (4-digit) level in 474 healthy Koreans. HLA genotyping was performed in two steps.

An efficient and reliable DNA extraction method for preimplantation genetic diagnosis: a comparison of allele drop out and amplification rates using different single cell lysis methods.

Objective: To evaluate methods of DNA extraction from single cells for their suitability to amplify and provide a correct diagnosis of target disease genes.

Design: Experimental study.

Setting: University hospital laboratory.

Haplotype analysis of killer cell immunoglobulin-like receptor genes in 77 Korean families.

Killer cell immunoglobulin-like receptor (KIR) genes constitute a multigene family whose genomic diversity is achieved through variation in gene content and allelic polymorphism within individual KIR genes. To date, 16 KIR genes and pseudogenes have been identified, and group A and group B haplotypes are characterized by a dominance of genes encoding inhibitory and activating receptors, respectively. In the present study, we have investigated the presence or absence of 16 KIR genes and pseudogenes and subtypes of four genes (3DP1, 3DP1 variant; 2DL1, 2DL1 variant; expressed and nonexpressed variant of 2DL5; full length and deleted form of 2DS4) in 352 members of 77 unrelated Korean families using a PCR-based sequence-specific priming method.