• Clinical and Experimental Reproductive Medicine
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• v.37 no.3
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• pp.199-206
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• 2010

Stem-cell therapy has the potential to improve vision in patients with untreatable retinal disease. Various types of cell source including fetal, embryonic and adult stem cells, intrinsic and extrinsic factors for differentiation into retinal progenitors and transplantation mode were discussed in this review. Experimental approaches have successfully induced photoreceptor precursor cells and retinal pigment epithelium. Stem-cell-based therapy is a promising treatment to restore vision in patients with retinal disease, in spite of the challenges.

• Toxicological Research
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• v.19 no.2
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• pp.153-159
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• 2003

Localization of mercury compounds was investigated in selective regions of the male reproductive tract using autometallography. The results demonstrated that mercury was observed in Sertoli and Leydig cells in testis, but not in the epithelial cells of rete testis and germ cells. In the efferent ductule, mercury compounds were observed in the cytoplasmic compartments of epithelial cells in the proximal and common regions, while they were observed in the supranuclear cytoplasmic compartments in the conus region. In the epididymis, the compounds were observed in the cytoplasmic compariments of narrow and basal cells, but not in the principal cells of the initial segment. In contrast, the compounds were evenly detected in the cytoplasmic compartments of principal cells in the caput. In the corpus and caudal epididymis, the compounds were observed in the basal region of principal cells. The data shows that mercury is differentially accumulated in the male reproductive tract in a region-specific manner.

• Journal of Microbiology and Biotechnology
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• v.13 no.4
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• pp.495-500
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• 2003

Tight junctions (TJ) between adjacent Sertoli cells in testis are important for the formation of the blood testis barrier (BTB). In an effort to verify the reproductive health risk of endocrine-active chemicals (EACs), changes in the transepithelial electrical resistance (TER) and the expression of TJ genes were examined by co-planar polychlorinated biphenyl (PCB) treatment in cultured mouse Sertoli cells. Although the increase in TER of Sertoli cells was accelerated by 10 nM co-planar PCB, it was downregulated by 100 nM co-planar PCB. The expression of claudin-1 was downregulated by co-planar PCB in a concentration-dependent manner. On the contrary, the expression of claudin-1 was increased in the Sertoli cells by 10 nM co-planar PCB treatment. These results suggest that the structure and function of TJ may be targeted by co-planar PCB in Sertoli cells. Assessment of the structure and function of TJ in Sertoli cells might be useful for screening the reproductive health risk of EACs.

• Clinical and Experimental Reproductive Medicine
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• v.48 no.4
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• pp.273-282
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• 2021

Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly, resulting in a pandemic. The virus enters host cells through angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2). These enzymes are widely expressed in reproductive organs; hence, coronavirus disease 2019 (COVID-19) could also impact human reproduction. Current evidence suggests that sperm cells may provide an inadequate environment for the virus to penetrate and spread. Oocytes within antral follicles are surrounded by cumulus cells, which rarely express ACE2 and TMPRSS2. Thus, the possibility of transmission of the virus through sexual intercourse and assisted reproductive techniques seems unlikely. Early human embryos express coronavirus entry receptors and proteases, implying that human embryos are potentially vulnerable to SARS-CoV-2 in the early stages of development. Data on the expression of ACE2 and TMPRSS2 in the human endometrium are sparse. Moreover, it remains unclear whether SARS-CoV-2 directly affects the embryo and its implantation. A study of the effect of SARS-CoV-2 on pregnancy showed an increase in preterm delivery. Thus, vertical transmission of the virus from mother to fetus in the third trimester is possible, and further data on human reproduction are required to establish this possibility. Based on analyses of existing data, major organizations in this field have published guidelines on the treatment of infertility. Regarding these guidelines, despite the COVID-19 pandemic, reproductive treatment is crucial for the well-being of society and must be continued under suitable regulations and good standard laboratory practice protocols.

• Clinical and Experimental Reproductive Medicine
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• v.42 no.2
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• pp.33-44
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• 2015

The generation of artificial gametes is a real challenge for the scientific community today. In vitro development of human eggs and sperm will pave the way for the understanding of the complex process of human gametogenesis and will provide with human gametes for the study of infertility and the onset of some inherited disorders. However, the great promise of artificial gametes resides in their future application on reproductive treatments for all these people wishing to have genetically related children and for which gamete donation is now their unique option of parenthood. This is the case of infertile patients devoid of suitable gametes, same sex couples, singles and those fertile couples in a high risk of transmitting serious diseases to their progeny. In the search of the best method to obtain artificial gametes, many researchers have successfully obtained human germ cell-like cells from stem cells at different stages of differentiation. In the near future, this field will evolve to new methods providing not only viable but also functional and safe artificial germ cells. These artificial sperm and eggs should be able to recapitulate all the genetic and epigenetic processes needed for the correct gametogenesis, fertilization and embryogenesis leading to the birth of a healthy and fertile newborn.

• Clinical and Experimental Reproductive Medicine
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• v.39 no.3
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• pp.95-106
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• 2012

It has been revealed that multiple cohorts of tertiary follicles develop during some animal estrous cycle and the human menstrual cycle. To reach developmental competence, oocytes need the support of somatic cells. During embryogenesis, the primordial germ cells appear, travel to the gonadal rudiments, and form follicles. The female germ cells develop within the somatic cells of the ovary, granulosa cells, and theca cells. How the oocyte and follicle cells support each other has been seriously studied. The latest technologies in genes and proteins and genetic engineering have allowed us to collect a great deal of information about folliculogenesis. For example, a few web pages (http://www.ncbi.nlm. nih.gov; http://mrg.genetics.washington.edu) provide access to databases of genomes, sequences of transcriptomes, and various tools for analyzing and discovering genes important in ovarian development. Formation of the antrum (tertiary follicle) is the final phase of folliculogenesis and the transition from intraovarian to extraovian regulation. This final step coordinates with the hypothalamic-pituitary-ovarian axis. On the other hand, currently, follicle physiology is under intense investigation, as little is known about how to overcome women's ovarian problems or how to develop competent oocytes from in vitro follicle culture or transplantation. In this review, some of the known roles of hormones and some of the genes involved in tertiary follicle growth and the general characteristics of tertiary follicles are summarized. In addition, in vitro culture of tertiary follicles is also discussed as a study model and an assisted reproductive technology model.

• Clinical and Experimental Reproductive Medicine
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• v.40 no.3
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• pp.107-114
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• 2013

Homeobox genes play essential roles in embryonic development and reproduction. Recently, a large cluster of homeobox genes, reproductive homeobox genes on the X chromosome (Rhox) genes, was discovered as three gene clusters, ${\alpha}$, ${\beta}$, and ${\gamma}$ in mice. It was found that Rhox genes were selectively expressed in reproduction-associated tissues, such as those of the testes, epididymis, ovaries, and placenta. Hence, it was proposed that Rhox genes are important for regulating various reproductive features, especially gametogenesis in male as well as in female mammals. It was first determined that 12 Rhox genes are clustered into ${\alpha}$ (Rhox1-4), ${\beta}$ (Rhox5-9), and ${\gamma}$ (Rhox10-12) subclusters, and recently Rhox13 has also been found. At present, 33 Rhox genes have been identified in the mouse genome, 11 in the rat, and three in the human. Rhox genes are also responsible for embryonic development, with considerable amounts of Rhox expression in trophoblasts, placenta tissue, embryonic stem cells, and primordial germ cells. In this article we summarized the current understanding of Rhox family genes involved in reproduction and embryonic development and elucidated a previously unreported cell-specific expression in ovarian cells.

• Development and Reproduction
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• v.20 no.1
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• pp.63-71
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• 2016

Human embryonic stem cells (hESCs) have been routinely cultured on mouse embryonic fibroblast feeder layers with a medium containing animal materials. For clinical application of hESCs, animal-derived products from the animal feeder cells, animal substrates such as gelatin or Matrigel and animal serum are strictly to be eliminated in the culture system. In this study, we performed that SNUhES32 and H1 were cultured on human amniotic fluid cells (hAFCs) with KO-SR XenoFree and a humanized substrate. All of hESCs were relatively well propagated on hAFCs feeders with xeno-free conditions and they expressed pluripotent stem cell markers, alkaline phosphatase, SSEA-4, TRA1-60, TRA1-81, Oct-4, and Nanog like hESCs cultured on STO or human foreskin fibroblast feeders. In addition, we observed the expression of nonhuman N-glycolylneuraminic acid (Neu5GC) molecules by flow cytometry, which was xenotransplantation components of contamination in hESCs cultured on animal feeder conditions, was not detected in this xeno-free condition. In conclusion, SNUhES32 and H1 could be maintained on hAFCs for humanized culture conditions, therefore, we suggested that new xeno-free conditions for clinical grade hESCs culture will be useful data in future clinical studies.

• Development and Reproduction
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• v.27 no.4
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• pp.185-193
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• 2023

Although increasing evidence of cause-and-effect relationship between BPA exposure and female reproductive disorders have been suggested through many studies, the precise biochemical and molecular mechanism(s) by which BPA interferes with steroidogenesis in the ovarian cells still remain unclear. Therefore, the purpose of this study was to discover the steroidogenic biomarker(s) associated with BPA treatment in human granulosa cell line, KGN. In this study, our results obtained via the analysis of steroidogenesis-related protein expression in KGN cells using quantitative polymerase chain reaction (qPCR) and western blot analyses revealed that the expression levels of steroidogenic acute regulatory (StAR) and aromatase decreased considerably and gradually after BPA treatment in a dose-dependent manner under BPA treatment. Further, remarkable decreases in their expression levels at the cellular levels were also confirmed via immunocytochemistry, and subsequent StAR and aromatase mRNA expression levels showed profiles similar to those observed for their proteins, i.e., both StAR and aromatase mRNA expression levels were significantly decreased under BPA treatment at concentrations ≥0.1 μM. We observed that follicle stimulating hormone upregulated StAR and aromatase protein expression levels; however, this effect was suppressed in the presence of BPA. Regarding the steroidogenic effects of BPA on KGN cells, controversies remain regarding the ultimate outcomes. Nevertheless, we believe that the results here presented imply that KGN cells have a good cellular and steroidogenic machinery for evaluating endocrine disruption. Therefore, StAR and aromatase could be stable and sensitive biomarkers in KGN cells for the cellular screening of the potential risk posed by exogenous and environmental chemicals to female reproductive (endocrine) function.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8975-8979
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• 2014

Objective: To explore the possible significance of aromatase P450 in endometrial hyperplasia with a background of polycystic ovary syndrome (PCOS). Methods: Immunohistochemistry was used to determine the expression of aromatase P450 in endometrium of PCOS patients. Semiquantitative analysis of aromatase P450 expression of mRNA and protein level wasalso carried out by real-time quantitative RT-PCR method. After endometrial cells were stimulated by testosterone and letrozole in vitro, the estradiol ($E_2$) level was determined, and the expression of cell aromatase P450 mRNA was assessed. Results: The aromatase P450 mRNA level was increased in endometria of PCOS patients. When endometrial cells were cultured with $10^{-6}M$ testosterone, the $E_2$ level in the culture medium increased. An inhibitory effect on $E_2$ generation and expression of aromatase P450 mRNA was observed when the endometrial cells were treated with $10^{-5}M$ letrozole. Conclusions: There is an increased expression of aromatase P450 in PCOS patient endometrium. Androgen stimulation could enhance the synthesis of aromatase P450 mRNA and the production of $E_2$ in endometrial cells in vitro while letrozole could do the reverse.