Androgen in the Uterus: A Compensator of Estrogen and Progesterone

전용필,이동목,전태훈,이기호,최인호 한국발생생물학회 2009 발생과 생식 Vol.13 No.3

Pivotal roles of steroid hormones in uterine endometrial function are well established from the mouse models carrying the null mutation of their receptors. Literally androgen belongs to male but interestingly it also detected in female. The fluctuations of androgen levels are observed during reproductive cycle and pregnancy, and the functional androgen receptor is expressed in reproductive organs including uterus. Using high throughput methodology, the downstream genes of androgen have been isolated and revealed correlations between other steroid hormones. In androgen-deficient mice, uterine responses to exogenous gonadotropins are impaired and the number of pups per litter is reduced dramatically. As expected androgen has important role in decidual differentiation through AR. It regulates specific gene network during those cellular responses. Recently we examined the effects of steroid hormonal complex containing high level of androgen. Interestingly, on the contrary to the androgen-alone administration, the hormonal complex did not disturb the decidual reaction and the pubs did not show any morphological abnormality. It is suspected that the complexity of communication between other steroid hormone and their receptors are the reasons. In summary, androgen exists in female blood and it suggests the importance of androgen in female reproduction. However, the complex interactions with other hormones are not fully understood compared with estrogen and progesterone. The further studies to evaluate the possible role of androgen are needed and important to provide the in vivo rational for the prevention of associated pregnancy complications and help human’s health.

Development of Spring Unit to Reduce Drive Space and Thickness of IT Application and Its Experimental Verification

전용필,강충길,서형윤,김종덕 한국정밀공학회 2012 International Journal of Precision Engineering and Vol. No.

The size and design of a slider phone, which is one of the most important IT applications, are strongly affected by the deformation of the spring unit and the interface for PCB-to-PCB connection located in the same drive space. This implies that the components contribute to the enhancement of the degree of freedom in the design. Past technical developments have focused on thickness and cost reduction, but no fundamental research has been performed on the design. We propose a spring unit in which the interface is integrated with the spring unit in order to share the drive space. Finally, the degree of freedom of the H/W PCB artwork can be enhanced on the basis of the disposition of parts that have major functions. Therefore, a simplified spring that is capable of unifying the interface with the spring unit is proposed, and the type of interface appropriate for this study is identified. Finally, five spring unit samples are evaluated by testing the mechanical performance on the basis of the sliding force; further, reliability tests are performed to examine the life cycle, and environmental tests such as the thermal shock and salt-spray tests are performed after assembling the spring unit of the mock-up phone.

임신한 생쥐 자궁에서의 doc-1 발현

전용필,Cheon, Yong-Pil 대한생식의학회 2002 Clinical and Experimental Reproductive Medicine Vol.29 No.4

Uterine cells carry out proliferation and differentiation for preparation the embryonic implantation during pregnancy. Therefore regulation of the cell proliferation is an essential step for uterine preparation, but there is not much information about the proliferation related genes in pregnant uterus. To identify these implantation specific genes, a PCR-select cDNA subtraction method was employed and got a few genes. One of the identified genes is a novel gene encoding oral tumor suppressor doc-1. To detect the doc-1 expression on the pregnant uterus, dot blotting, RT-PCR, and in situ hybridization were employed. Dot blotting revealed that doc-1 mRNA expression increase after implantation. During normal pregnancy, doc-1 mRNA expression was detected as early as day 1 of pregnancy with RT-PCR. Its expression was increased about 15 times after embryonic implantation. doc-1 transcript was localized in luminal epithelial cells but it was very faint during preimplantation. After starting the implantation, it localized in the stromal cells; heightened expression of doc-1 correlates with intense stromal cell proliferation surrounding the implanting blastocyst on day 6 morning. However in the decidualized cells, the intensity of localized doc-1 mRNA was weak. From those results, it is revealed that doc-1 express at pregnant uterus of the mouse. In addition it is suggested that doc-1 is the gene regulating the proliferation of the luminal epithelial cells and stromal cells during early implantation and decidualization.

Altering of Collagens in Early Pregnant Mouse Uterus

전용필 한국발생생물학회 2007 발생과 생식 Vol.11 No.1

착상기 이전 자궁에서 특이적 자궁내막 준비가 진행되어야 하는데, 이는 자궁 내막의 점진적 분화로 배아의 착상과 성공적 임신에 절대적으로 필요하다. 배아 발생 동안에 관찰되는 조직의 재구성은 세포외 기질을 포함한 다양한 요인에 의해 조절된다. 임신 동안에 관찰되는 극적인 변화로는 배아의 이동, 탈락막 반응, 태반의 분화를 그 예로 들 수 있다. 배아와 자궁간의 성공적 착상을 위한 변화들은 배아와 자궁의 착상을 위한 능력 갖출 수 있도록 한다. 이러한 변화 Specific endometrial preparation should occur during periimplantation period. That is a progress of serial differentiation and is absolute in implantation of embryo and successful pregnancy. Remodeling of tissues shown during embryogenesis is regulated by various factors including extracellular matrix (ECM). Marked changes during pregnancy are including embryo migration, decidual response, and differentiation of placenta in placental animals including human. These changes to successful implantation in embryo and uterus have to prepare the competence for attachment of embryo and uterus, and invasion defense of uterus. During these changes, ECM dramatically changes for maintaining the uterine and embryonic functions. The major component of most connective tissue is collagens. It is very complex and hard to explore the mechanisms for ECM modulation. Recently using high throughput methodology, PCR-select cDNA subtraction method, microarray, many candidate genes have been identified. Steroid hormones have fundamental role in implantation and maintenance of pregnancy. Dermatopontin, a regulator of collagen accumulation, is regulated spatio-temporally in the uterus by primarily progesterone through progesterone receptors at the time of implantation. Modulation of extracellular matrix is critically regulated by cascade of gene net-works which are regulated by cascade of sex steroid hormones. Pathological regulation of uterine extracellular matrix reported in diabetic patients. To know the extracellular modulation is essential to understanding implantation, feto-placental development and overcome the paths involved in female reproduction. Though ECM composed with very various components and it is complex, the present review focused on the fate of collagens during periimplantation period.

여성생식기관에서 프로제스테론의 분자생물학적 기능

전용필,Cheon, Yong-Pil 대한생식의학회 2008 Clinical and Experimental Reproductive Medicine Vol.35 No.1

Effects of EGF and PAF on the Hatching and Implantation of Peri-implantation Stage Embryos

전용필 한국발생생물학회 2010 발생과 생식 Vol.14 No.1

A fertilized oocyte can get the competence for implantation through cleavage and stage-specific gene expression. These are under the control of autonomous and exogenous regulators including physiological culture condition. Endogenous and exogenous growth factors are considered as critical regulators of cleaving embryos during travel the oviduct and uterus. In this study, an effort was made to evaluate comprehensively the quality of embryos for implantation, grown in media enriched with EGF and PAF. The study evaluated developmental rates on given time, blastulation and hatching rates, and adhesion rates. Developmental rates of blastocyst to the hatching stage were significantly high in PAF treated group compared to the control in a dose-dependent manner but not in EGF group. Implantation rates were significantly high both PAF and EGF in a dose-dependent manner. H7, a PKC inhibitor, blocked the process of hatching of the blastocysts but combined treatment of EGF and PAF enhanced the hatching and implantation of blastocsyts. Based on these results it is suggested that EGF and PAF support acquirement of implantation competence at blastocyst stage through a PKC pathway.

G Protein Mediated Hatching Regulation in the Mouse Embryo

전용필 한국발생생물학회 2012 발생과 생식 Vol.16 No.1

Hatching occurred in the time dependent manners and strictly controlled. Although, the hatching processes are under the control of muti-embryotrophic factors and the expressed G proteins of cell generate integrated activation, the knowledge which GPCRs are expressed during hatching stage embryos are very limited. In the present study, which G proteins are involved was examined during blastocyst development to the hatching stage. The early-, expanded-, and lobe-stage blastocysts were treated with various Gα activators and H series inhibitors, and examined developmental patterns. Pertusis toxin (PTX) improved the hatching rate of the early-stage blastocyst and lobe-formed embryos. Cholera toxin (CTX) suppressed the hatching of the early-stage blastocyst and expanded embryos. The effects of toxins on hatching and embryo development were changed by the H7 and H8. These results mean that PTX mediated GPCRs activation is signaling generator in the nick or pore formation in the ZP. In addition, PTX mediated GPCR activation induces the locomotion of trophectoderm for the escaping. CTX mediate GPCRs activation is the cause of suppression of hatching processes. Based on these data, it is suggested that various GPCRs are expressed in the periimplantation stage embryos and the integration of the multiple signals decoding of various signals in a spatial and temporal manner regulate the hatching process.

당뇨병성 BBDP Rat에 있어서 난포내 난자의 핵상과 성숙

전용필,양제훈,김정훈,강병문,장윤석,목정은,김길수 한국실험동물학회 1998 한국실험동물학회 학술발표대회 논문집 Vol.1998 No.-

Spermatozoa Characteristics of Streptozotocin-induced Diabetic Wistar Rat: Acrosome Reaction and Spermatozoa Concentration

전용필,김정훈,강병문,장윤석,남주현,김영수,계명찬,김문규,김길수,Cheon, Yong-Pil,Kim, Chung-Hoon,Kang, Byung-Moon,Chang, Yoon-Seok,Nam, Joo-Hyun,Kim, Young-Soo,Gye, Myung-Chan,Kim, Moon-Kyoo,Kim, Kil-Soo The Korean Society for Reproductive Medicine 1999 Clinical and Experimental Reproductive Medicine Vol.26 No.1

당뇨병은 생식내분비 조직의 구조나 기능 변화를 유발하여 호르몬 합성 및 분비량의 변화를 야기하고, 정자의 운동성 등에 영향을 미치는 것으로 알려져 왔다. 그러나 부정소와 수정관내 정자의 농도 변화나 수정능력 획득 및 침체반응에 미치는 영향은 잘 알려져 있지 않다. 본 실험에서는 Wistar 쥐에 streptozotocin을 투여하여 당뇨병을 유발시킨 후 3일과 14일에 부정소 각 부위와 수정관내 정자 농도 변화를 조사하고 부정소 꼬리와 수정관내 정자의 침체반응 유도 실험 (acrosome reaction to ionophore challenge test, ARIC test)을 이용하여 정자의 수정 능력을 평가하였다. Streptozotocin을 주사한 후 혈액내 인슐린 및 포도당 농도는 당뇨병 경과 기간이 길어짐에 따라 반비례 관계를 보였다. 부정소 머리와 몸통내 정자의 농도는 3일군에서부터 감소하기 시작하나 꼬리에서는 14일군 $(15.2{\pm}2.1)$에서 대조군 $(28.1{\pm}4.0)$이나 3일군에 $(24.8{\pm}2.9)$비해 유의하게 감소하였다. 수정관내 절자 농도는 14일군이 $0.025{\pm}0.013$으로 대조군과 $(0.108{\pm}0.03)$ 3일군에 $(0.067{\pm}0.046)$ 비해 유의하게 감소하였으며, 3일군도 대조군에 비해 유의한 차이를 보였다. 자발적 첨체반응율은 대조군의 부정소 꼬리정자는 $37.1{\pm}2.4$이고 수정관내 정자는 $49.3{\pm}2.4$로 두 부위간 유의한 차이를 보였다. 3일군과 14일군의 부정소 꼬리와 수정관내 정자의 자발적 첨체반응율은 대조군에 비해 유의하게 증가하였다. 한편 14일군의 수정관내 정자의 자발적 첨체반응율은 대조군이나 3일군에 비해 유의하게 증가하였다. ARIC test 결과 대조군과 3일군에서는 20%이상 차이를 보였으나 14일군에서는 약 8.4% 차이를 보였다. 위의 결과가 부정소의 성숙 조절기능 이상 또는 정자형성 이상에 기인한 것인지는 더 연구되어야 하나 당뇨병 병력이 길어짐에 따라 정자의 수적인 감소, 자발적 침체반응의 증가나 침체반응의 약화가 유발되어 생식능력의 감소 원인으로 작용하는 것으로 사료된다. Some of the information concerning sexual function in the male diabetes has been focused upon the problems of endocrine or semen parameters. However, the characteristics of acrosome reaction and spermatozoa concentration at the epididymis and vas deferens have scarcely been studied, and the causes of the infertility has not been critically identified. So, we designed to inspect the spermatozoa concentration and the characteristics of acrosome reaction at epididymis and vas deferens of diabetic Wistar rat induced by streptozotocin (STZ, 70 mg/kg, ip). Experimental animal was sacrificed at 3 days and 14 days after the STZ injection. In the diabetes-induced rat, the levels of insulin and glucose had a pattern of inverse proportion. The spermatozoa concentrations in caput and corpus epididymis were significantly decreased in all diabetic condition. In cauda epididymis, however, there was significant decrease in sperm concentration at 14 days onward. In diabetic rat, the spontaneous reaction rate of spermatozoa of cauda and vas deferens were significantly higher than the control group. The ARIC (acrosome reaction to ionophore challenge) value of caudal sperm was 28.7 at control, 22.1 at 3 days, and 8.3 at 14 days. In the present study the spermatozoa concentration was decreased and the spontaneous reaction rate was increased by diabetes. In ARIC-test, it is revealed that the fertility of spermatozoa of 14 days group was lower than control or 3 days group. Diabetes mellitus may be provoke the decreased fertilization rate and subsequent infertility and subsequent infertility.

Expression Profiles of Secretory Leucocyte Protease Inhibitor, MMP9, and Neutrophil Elastase in the Mouse Uterus

전용필 한국발생생물학회 2010 발생과 생식 Vol.14 No.3

The tremendous changes of uterine endometrium is observed during early pregnancy and protease and their inhibitors are involved in regulation of cell proliferation and remodeling of the tissues through remodeling the extracellular matrix (ECM). Some of the proteases and protease inhibitors have been suspected to a factor in endometrial changes but many parts of their expression profiles and the physiological roles are not uncovered. To evaluate the functional roles of them, in this study the expression profiles of proteases and protease inhibitors were analyzed using real-time quantitative PCR analysis. Mmp9 (matrix metalloproteinase 9) mRNA levels peaked on day 4 at the time of implantation. On the other hand, Ela2 (neutrophil elastase, NE) mRNA levels were peaked on day 2 of pregnancy. Its expression were decreased until day 4 of pregnancy but increased rapidly until day 7 of pregnancy and decreased again. NE inhibitor Slpi (secretory leukocyte protease inhibitor, SLPI) mRNA levels were related with the implantation stage and with the levels of Ela2. At the time of implantation the expression levels of Slpi mRNA were about 5 times higher than the Ela2 mRNA in the uterus. In the implantation stage embryos, Mmp9 specific mRNA was only detected at the blastocyst. On the other hand, the expression level of SLPI was higher than that of the Ela2 mRNA at blastocyst and 4.5day p.c. embryos. Based on these results it is suggested that MMP9, SLPI, and NE have important physiological role in embryo implantation both in uterus and embryos.