Pub Date : 2025-12-01Epub Date: 2025-12-31DOI: 10.12717/DR.2025.29.4.137
Hyunhee Song, Jae-Wan Jung, Hoon Jang
Nitrogen-doped Carbon Quantum Dots (NCQDs) exhibit distinctive optical properties and potential bioactivity in mammalian systems. However, their effects on reproductive cells remain poorly understood. To clarify their role in gamete function and embryo development, the present study examined the influence of NCQDs on sperm activation, fertilization, and early embryo development in vitro using a mouse model. At a low concentration (10 µg/mL), NCQDs exposure markedly enhanced sperm motility, survival, and capacitation, as determined by computer-assisted sperm analysis (CASA). These functional improvements significantly increased fertilization rates and enhanced embryonic development up to the morula stage. In contrast, blastocyst formation was delayed, accompanied by reduced pluripotency (Oct4) and trophectoderm differentiation (Cdx2, Tead2). Elevated mRNA expression of endoplasmic reticulum (ER) stress markers (Atf6, Chop) in morula-stage embryos suggested that prolonged NCQD exposure induces cellular stress that may interfere with lineage specification. Collectively, these findings reveal a stage-specific, biphasic effect of NCQDs, promoting sperm activation and early cleavage while inhibiting later differentiation, highlighting the need for optimized dosing and exposure timing to safely harness their reproductive benefits.
{"title":"Nitrogen-Doped Carbon Quantum Dots Enhance In Vitro Fertilization and Early Embryo Development by Improving Sperm Activation in Mice.","authors":"Hyunhee Song, Jae-Wan Jung, Hoon Jang","doi":"10.12717/DR.2025.29.4.137","DOIUrl":"10.12717/DR.2025.29.4.137","url":null,"abstract":"<p><p>Nitrogen-doped Carbon Quantum Dots (NCQDs) exhibit distinctive optical properties and potential bioactivity in mammalian systems. However, their effects on reproductive cells remain poorly understood. To clarify their role in gamete function and embryo development, the present study examined the influence of NCQDs on sperm activation, fertilization, and early embryo development <i>in vitro</i> using a mouse model. At a low concentration (10 µg/mL), NCQDs exposure markedly enhanced sperm motility, survival, and capacitation, as determined by computer-assisted sperm analysis (CASA). These functional improvements significantly increased fertilization rates and enhanced embryonic development up to the morula stage. In contrast, blastocyst formation was delayed, accompanied by reduced pluripotency (<i>Oct4</i>) and trophectoderm differentiation (<i>Cdx2, Tead2</i>). Elevated mRNA expression of endoplasmic reticulum (ER) stress markers (<i>Atf6, Chop</i>) in morula-stage embryos suggested that prolonged NCQD exposure induces cellular stress that may interfere with lineage specification. Collectively, these findings reveal a stage-specific, biphasic effect of NCQDs, promoting sperm activation and early cleavage while inhibiting later differentiation, highlighting the need for optimized dosing and exposure timing to safely harness their reproductive benefits.</p>","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"29 4","pages":"137-149"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12821385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146031832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-12-31DOI: 10.12717/DR.2025.29.4.121
Eun-Young Jeon, Sung-Ho Lee
Little is known about the regulation of gene expression related to the hypothalamus-pituitary (HP) axis around the onset of normal puberty. In the present study, we examined the expression profiles of genes in HP hormone circuit on every other day from postnatal day (PND) 29 to PND 43. Average vaginal opening (VO) date was PND 37 (66%), and the weight of reproductive organs increased significantly from PND 37. Serum steroid hormone levels significantly increased on PND 39. The appearance of a number of Graafian follicles and corpora lutea on PND 37. Generally, our polymerase chain reactions (PCR) results showed that most of the expression of hypothalamus and pituitary factors tended to increase after VO, and the patterns were rather unstable and no significant peak pattern such as LH surge shown in proestrus adults. The mRNA levels of gonadotropin-inhibitory hormone (GnIH)-GPR147 and neurokinin B(Tac)-TacR3 mostly reached a peak in the last period of the experimental schedule. In pituitary, mRNA level of gonadotropin subunits (Cgα, LH-β and FSH-β) also significantly increased on later experimental period. In conclusion, we could confirm the rapid growth and maturation of reproductive organs immediately after VO, and dynamic changes in gene expression of the HP axis factors. The gene expression patterns at peripubertal period were incomplete and unstable without showing the preovulatory LH surge-related gene expression pattern in adults. The present study on neuroendocrine control of peripubertal sexual maturation may offer a basis for understanding normo- and/or patho-physiological status of puberty.
{"title":"Activity Changes of the Hypothalamus-Pituitary Hormonal Axis in Peripubertal Female Rats.","authors":"Eun-Young Jeon, Sung-Ho Lee","doi":"10.12717/DR.2025.29.4.121","DOIUrl":"10.12717/DR.2025.29.4.121","url":null,"abstract":"<p><p>Little is known about the regulation of gene expression related to the hypothalamus-pituitary (HP) axis around the onset of normal puberty. In the present study, we examined the expression profiles of genes in HP hormone circuit on every other day from postnatal day (PND) 29 to PND 43. Average vaginal opening (VO) date was PND 37 (66%), and the weight of reproductive organs increased significantly from PND 37. Serum steroid hormone levels significantly increased on PND 39. The appearance of a number of Graafian follicles and corpora lutea on PND 37. Generally, our polymerase chain reactions (PCR) results showed that most of the expression of hypothalamus and pituitary factors tended to increase after VO, and the patterns were rather unstable and no significant peak pattern such as LH surge shown in proestrus adults. The mRNA levels of gonadotropin-inhibitory hormone (GnIH)-GPR147 and neurokinin B(Tac)-TacR3 mostly reached a peak in the last period of the experimental schedule. In pituitary, mRNA level of gonadotropin subunits (Cgα, LH-β and FSH-β) also significantly increased on later experimental period. In conclusion, we could confirm the rapid growth and maturation of reproductive organs immediately after VO, and dynamic changes in gene expression of the HP axis factors. The gene expression patterns at peripubertal period were incomplete and unstable without showing the preovulatory LH surge-related gene expression pattern in adults. The present study on neuroendocrine control of peripubertal sexual maturation may offer a basis for understanding normo- and/or patho-physiological status of puberty.</p>","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"29 4","pages":"121-135"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12821383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146031839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-12-31DOI: 10.12717/DR.2025.29.4.161
Bo Ryung Park, Sung Jun Lee, Jeong Hee Yoon, Ji Eun Ha, Dong Woo Kim, Jeong Hee Min, Se Ryun Kwon, Joon Yeong Kwon
The body color of crustaceans is an important factor influencing consumer preference and marketability, expressed through the accumulation of carotenoids within the body. However, crustaceans cannot synthesize carotenoids internally and rely entirely on dietary sourcess. Deficiency of this pigment can lead to poor body coloration. Haematococcus lacustris is a species of freshwater microalgae that accumulates astaxanthin at high concentrations, possessing significant industrial potential as a natural source of carotenoids. This study investigated the effects of adding H. lacustris, which is rich in astaxanthin, to feed on improving body color and health status in Macrobrachium rosenbergii post-larvae. The experimental results showed that body length exhibited similar growth trends across all groups, while body weight was significantly higher in the control (CON) group compared with the low concentration (LC) and high concentrations (HC) groups. Feed supplemented with H. lacustris exhibited a darkening effect on body color depending on concentration, and this effect persisted even after heating. Superoxide dismutase (SOD) expression levels in the hepatopancreas significantly increased at day 60 in the HC group. Crustin expression also significantly increased in the hepatopancreas on day 60, but no significant differences were observed between groups in the tail muscle. The addition of H. lacustris to the diet aided in the body color development of M. rosenbergii post-larvae, suggesting that this approach may also be applicable to the body color development of various crustaceans.
{"title":"Effects of <i>Haematococcus lacustris</i>-Supplemented Diets on the Development of Body Color and Health of Giant Freshwater Prawn (<i>Macrobrachium rosenbergii</i>).","authors":"Bo Ryung Park, Sung Jun Lee, Jeong Hee Yoon, Ji Eun Ha, Dong Woo Kim, Jeong Hee Min, Se Ryun Kwon, Joon Yeong Kwon","doi":"10.12717/DR.2025.29.4.161","DOIUrl":"10.12717/DR.2025.29.4.161","url":null,"abstract":"<p><p>The body color of crustaceans is an important factor influencing consumer preference and marketability, expressed through the accumulation of carotenoids within the body. However, crustaceans cannot synthesize carotenoids internally and rely entirely on dietary sourcess. Deficiency of this pigment can lead to poor body coloration. <i>Haematococcus lacustris</i> is a species of freshwater microalgae that accumulates astaxanthin at high concentrations, possessing significant industrial potential as a natural source of carotenoids. This study investigated the effects of adding <i>H. lacustris</i>, which is rich in astaxanthin, to feed on improving body color and health status in <i>Macrobrachium rosenbergii</i> post-larvae. The experimental results showed that body length exhibited similar growth trends across all groups, while body weight was significantly higher in the control (CON) group compared with the low concentration (LC) and high concentrations (HC) groups. Feed supplemented with <i>H. lacustris</i> exhibited a darkening effect on body color depending on concentration, and this effect persisted even after heating. Superoxide dismutase (SOD) expression levels in the hepatopancreas significantly increased at day 60 in the HC group. Crustin expression also significantly increased in the hepatopancreas on day 60, but no significant differences were observed between groups in the tail muscle. The addition of <i>H. lacustris</i> to the diet aided in the body color development of <i>M. rosenbergii</i> post-larvae, suggesting that this approach may also be applicable to the body color development of various crustaceans.</p>","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"29 4","pages":"161-174"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12821380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146031842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-12-31DOI: 10.12717/DR.2025.29.4.105
Sohyeon Moon, Soohyung Lee, Youngsok Choi
The Hippo signaling pathway is an evolutionarily conserved pathway from Drosophila to humans. Although key elements of the Hippo signaling pathway are well-defined, the factors that control the transcriptional outcome of Hippo have yet to be fully elucidated. Until now, mainly in mammals, the Hippo signaling pathway has been focused on serine 127 (S127) of yes-associated protein (YAP), a key target gene. Recently, it has been shown that nemo-like kinase (NLK) can crosstalk with the Hippo pathway by phosphorylating an unknown new site of YAP. NLK transfers YAP serine 128 (S128) to the nucleus through dissociation of the 14-3-3 binding with YAP, promoting transcriptional activity. However, this is worth investigating as it has not been studied in the mammalian reproductive system and the precise mechanisms of signaling pathway crosstalk in endometrial cells that are dynamically altered by steroid hormones remain unclear. In this study, we found that expression of NLK and YAP S128 changes the expression site or extent of expression in the endometrium during the estrous cycle. Furthermore, we demonstrated that regulation of its expression proceeds through estrogen and its receptors. We have shown that these responses are triggered and regulated in uterine epithelial cells, suggesting that their expression plays a role in uterine dynamics during the estrous cycle, as does the hippocampal signaling pathway.
{"title":"Crosstalk of Nemo-Like Kinase (NLK) and Yes-Associated Protein (YAP) Phosphorylation in Endometrial Epithelial Cells.","authors":"Sohyeon Moon, Soohyung Lee, Youngsok Choi","doi":"10.12717/DR.2025.29.4.105","DOIUrl":"10.12717/DR.2025.29.4.105","url":null,"abstract":"<p><p>The Hippo signaling pathway is an evolutionarily conserved pathway from Drosophila to humans. Although key elements of the Hippo signaling pathway are well-defined, the factors that control the transcriptional outcome of Hippo have yet to be fully elucidated. Until now, mainly in mammals, the Hippo signaling pathway has been focused on serine 127 (S127) of yes-associated protein (YAP), a key target gene. Recently, it has been shown that nemo-like kinase (NLK) can crosstalk with the Hippo pathway by phosphorylating an unknown new site of YAP. NLK transfers YAP serine 128 (S128) to the nucleus through dissociation of the 14-3-3 binding with YAP, promoting transcriptional activity. However, this is worth investigating as it has not been studied in the mammalian reproductive system and the precise mechanisms of signaling pathway crosstalk in endometrial cells that are dynamically altered by steroid hormones remain unclear. In this study, we found that expression of NLK and YAP S128 changes the expression site or extent of expression in the endometrium during the estrous cycle. Furthermore, we demonstrated that regulation of its expression proceeds through estrogen and its receptors. We have shown that these responses are triggered and regulated in uterine epithelial cells, suggesting that their expression plays a role in uterine dynamics during the estrous cycle, as does the hippocampal signaling pathway.</p>","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"29 4","pages":"105-119"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12821382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146031784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-12-31DOI: 10.12717/DR.2025.29.4.151
Ye Rim Kim, Hyun Woo Choi
Generation of primordial germ cell-like cells (PGCLCs) from pluripotent stem cells in vitro serve as key intermediates in the modeling of germline development. While previous studies have predominantly focused on the induction of PGCLCs from epiblast-like cells (EpiLCs), recent studies suggest that BMP4 signaling can also drive PGCLC specification from epiblast stem cells (EpiSCs). However, the efficiency of PGCLC induction from EpiSCs remains suboptimal and underexplored. We hypothesized that the dimensional structure of the culture environment significantly influences the differentiation efficiency. To evaluate PGCLC induction efficiency, we used Blimp1-mVenus×Stella-ECFP (BVSC) transgenic reporter embryonic stem cells. FACS analysis revealed that the proportion of Blimp1-mVenus+/Stella-ECFP+ double-positive PGCLCs was significantly higher in the 3D aggregate culture compared to the 2D monolayer system. Our findings demonstrate that a 3D culture environment enhances the efficiency of PGCLC induction from mouse EpiSCs compared to a 2D monolayer system. These results highlight the importance of culture dimensionality in optimizing germ cell differentiation protocols and provide a useful framework for further studies on germline development.
{"title":"Induction of Primordial Germ Cell Like Cell from Mouse Epiblast Stem Cells in Three-Dimensional Culture.","authors":"Ye Rim Kim, Hyun Woo Choi","doi":"10.12717/DR.2025.29.4.151","DOIUrl":"10.12717/DR.2025.29.4.151","url":null,"abstract":"<p><p>Generation of primordial germ cell-like cells (PGCLCs) from pluripotent stem cells <i>in vitro</i> serve as key intermediates in the modeling of germline development. While previous studies have predominantly focused on the induction of PGCLCs from epiblast-like cells (EpiLCs), recent studies suggest that BMP4 signaling can also drive PGCLC specification from epiblast stem cells (EpiSCs). However, the efficiency of PGCLC induction from EpiSCs remains suboptimal and underexplored. We hypothesized that the dimensional structure of the culture environment significantly influences the differentiation efficiency. To evaluate PGCLC induction efficiency, we used Blimp1-mVenus×Stella-ECFP (BVSC) transgenic reporter embryonic stem cells. FACS analysis revealed that the proportion of Blimp1-mVenus<sup>+</sup>/Stella-ECFP<sup>+</sup> double-positive PGCLCs was significantly higher in the 3D aggregate culture compared to the 2D monolayer system. Our findings demonstrate that a 3D culture environment enhances the efficiency of PGCLC induction from mouse EpiSCs compared to a 2D monolayer system. These results highlight the importance of culture dimensionality in optimizing germ cell differentiation protocols and provide a useful framework for further studies on germline development.</p>","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"29 4","pages":"151-160"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12821381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146031816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-09-30DOI: 10.12717/DR.2025.29.3.81
Mihae Song, Jeonghoon Han, Hea Ja Baek
Oxybenzone (Benzophenone-3; BP-3) is used as a component of sunscreens, and known to disrupt the endocrine system of marine organisms. This study evaluated BP-3 toxicity on Shimofuri goby (Tridentiger bifasciatus). We evaluated morphological changes during embryogenesis. In addition, hatching rate (HR) and embryo survival to hatching were assessed. Embryos were exposed to BP-3 in artificial seawater, and then they were randomly sampled every 12 hours for microscopic observation and cortisol analysis. 36 hours after exposure to BP-3 100 and 1,000 μg/L groups, the tail was not separated from the yolk sac. 72 hours after exposure, incompleted eye pigmentation was observed at 100 and 1,000 μg/L BP-3. After 48 and 60 hours of exposure, all individuals in the control group had elongated tails, whereas individuals in the all BP-3 treated group failed to elongate or showed signs of bent tails. Survival rate decreased dose-dependently (control: >90%) with LC50-96h=493 μg/L. HR significantly declined in all BP-3 groups in a dose-dependent manner. And, heartbeat was increased in response to BP-3 1,000 μg/L. High levels of cortisol were observed in the initial groups (0 hours) and decreased after 24 hours. The BP-3 100 and 1,000 μg/L showed significantly lower cortisol levels than the control at 96 hours of exposure. Overall, this study suggests that BP-3 can interfere with embryonic development, resulting in adverse effects on survival and HRs in T. bifasciatus embryos.
{"title":"Effect of Oxybenzone (Benzophenone-3) on Embryo Development in the Shimofuri Goby, <i>Tridentiger bifasciatus</i>.","authors":"Mihae Song, Jeonghoon Han, Hea Ja Baek","doi":"10.12717/DR.2025.29.3.81","DOIUrl":"10.12717/DR.2025.29.3.81","url":null,"abstract":"<p><p>Oxybenzone (Benzophenone-3; BP-3) is used as a component of sunscreens, and known to disrupt the endocrine system of marine organisms. This study evaluated BP-3 toxicity on Shimofuri goby (<i>Tridentiger bifasciatus</i>). We evaluated morphological changes during embryogenesis. In addition, hatching rate (HR) and embryo survival to hatching were assessed. Embryos were exposed to BP-3 in artificial seawater, and then they were randomly sampled every 12 hours for microscopic observation and cortisol analysis. 36 hours after exposure to BP-3 100 and 1,000 μg/L groups, the tail was not separated from the yolk sac. 72 hours after exposure, incompleted eye pigmentation was observed at 100 and 1,000 μg/L BP-3. After 48 and 60 hours of exposure, all individuals in the control group had elongated tails, whereas individuals in the all BP-3 treated group failed to elongate or showed signs of bent tails. Survival rate decreased dose-dependently (control: >90%) with LC<sub>50</sub>-96h=493 μg/L. HR significantly declined in all BP-3 groups in a dose-dependent manner. And, heartbeat was increased in response to BP-3 1,000 μg/L. High levels of cortisol were observed in the initial groups (0 hours) and decreased after 24 hours. The BP-3 100 and 1,000 μg/L showed significantly lower cortisol levels than the control at 96 hours of exposure. Overall, this study suggests that BP-3 can interfere with embryonic development, resulting in adverse effects on survival and HRs in <i>T. bifasciatus</i> embryos.</p>","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"29 3","pages":"81-94"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145350345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-09-30DOI: 10.12717/DR.2025.29.3.63
Ju-Hee Lim, Yong-Pil Cheon
The steroidogenic acute regulatory protein (StAR) governs the rate-limiting step of steroid hormone biosynthesis by facilitating cholesterol transfer from the outer mitochondrial membrane (OMM) to the inner mitochondrial membrane (IMM). This essential function initiates pregnenolone synthesis by P450 family 11 subfamily A member 1 (CYP11A1, cytochrome P450scc) within IMM. Beyond its biochemical role, StAR is a critical developmental protein, with spatiotemporally restricted expression during fetal adrenal and gonadal differentiation. Its activity is tightly regulated at multiple levels, including transcriptional control by transcription factors, GATA post-translational phosphorylation, mitochondrial targeting, and proteolytic degradation. Structurally, StAR functions through a dynamic molten globule-like conformation and a conserved StAR-related lipid transfer (START) domain that mediates cholesterol binding. StAR interacts with mitochondrial proteins such as nonselective voltage-gated ion channel VDAC (VDAC), translocator protein (TSPO), and ATPase family AAA domain-containing protein 3A (ATAD3A), forming part of the transduceosome complex that coordinates cholesterol transfer. Mutations in STAR, particularly within the START domain), cause lipoid congenital adrenal hyperplasia (CAH), a disorder marked by impaired steroidogenesis and disrupted endocrine organ development. This review integrates current knowledge on the molecular and developmental roles of STAR, emphasizing how its precise regulation is essential for embryonic steroidogenesis. Understanding StAR's function at the interface of lipid transport and organogenesis provides critical insight into congenital steroidogenic disorders and potential avenues for therapeutic intervention.
{"title":"The Steroidogenic Acute Regulatory (STAR) Gene Anatomy, Expression, and Roles.","authors":"Ju-Hee Lim, Yong-Pil Cheon","doi":"10.12717/DR.2025.29.3.63","DOIUrl":"10.12717/DR.2025.29.3.63","url":null,"abstract":"<p><p>The steroidogenic acute regulatory protein (StAR) governs the rate-limiting step of steroid hormone biosynthesis by facilitating cholesterol transfer from the outer mitochondrial membrane (OMM) to the inner mitochondrial membrane (IMM). This essential function initiates pregnenolone synthesis by P450 family 11 subfamily A member 1 (CYP11A1, cytochrome P450scc) within IMM. Beyond its biochemical role, StAR is a critical developmental protein, with spatiotemporally restricted expression during fetal adrenal and gonadal differentiation. Its activity is tightly regulated at multiple levels, including transcriptional control by transcription factors, GATA post-translational phosphorylation, mitochondrial targeting, and proteolytic degradation. Structurally, StAR functions through a dynamic molten globule-like conformation and a conserved StAR-related lipid transfer (START) domain that mediates cholesterol binding. StAR interacts with mitochondrial proteins such as nonselective voltage-gated ion channel VDAC (VDAC), translocator protein (TSPO), and ATPase family AAA domain-containing protein 3A (ATAD3A), forming part of the transduceosome complex that coordinates cholesterol transfer. Mutations in STAR, particularly within the START domain), cause lipoid congenital adrenal hyperplasia (CAH), a disorder marked by impaired steroidogenesis and disrupted endocrine organ development. This review integrates current knowledge on the molecular and developmental roles of STAR, emphasizing how its precise regulation is essential for embryonic steroidogenesis. Understanding StAR's function at the interface of lipid transport and organogenesis provides critical insight into congenital steroidogenic disorders and potential avenues for therapeutic intervention.</p>","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"29 3","pages":"63-80"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12527451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-09-30DOI: 10.12717/DR.2025.29.3.95
Ji Yeon Hong, Sang-Yeon Won, Jung Jin Lee, Jae-Ho Ryu, Youmi Park, Seok-Hyung Kim, Hyun-Ju Cho, Sang-Yeob Yeo
Neural progenitors of the ventral spinal cord differentiate into GABAergic Kolmer-Agduhr neurons (KA) under the control of Jagged2-meditated Notch signaling during late neurogenesis. Mib-mediated Notch signaling has also been demonstrated to regulate the number of KA neurons in the p3 domain. However, the relationship between Jagged2 and Mib during late neurogenesis remains unclear. Here we investigate how Mib is involved in the regulation of Jagged2 and the long-range Notch signaling. Ubiquitination of Jagged2 by Mib was found to promote its proteasome-dependent degradation in undifferentiated P19 cells, but not in differentiated P19 cells by retinoic acid. Co-IP assay revealed that Mib physically interacts with Jagged2, but not with the intracellular domain itself. Cell transplantation experiments showed that the formation of extracellular vesicles (EVs) containing Jagged2 was promoted by the co-expression of Mib. Our observations suggest that EVs containing Jagged2 and Mib may play a role in the Notch signaling in discrete compartments of the neural tube during the development of the vertebrate nervous system.
{"title":"Zebrafish Mib Promotes Long-Distance Transport of Jagged2 Via Extracellular Vesicles.","authors":"Ji Yeon Hong, Sang-Yeon Won, Jung Jin Lee, Jae-Ho Ryu, Youmi Park, Seok-Hyung Kim, Hyun-Ju Cho, Sang-Yeob Yeo","doi":"10.12717/DR.2025.29.3.95","DOIUrl":"10.12717/DR.2025.29.3.95","url":null,"abstract":"<p><p>Neural progenitors of the ventral spinal cord differentiate into GABAergic Kolmer-Agduhr neurons (KA) under the control of Jagged2-meditated Notch signaling during late neurogenesis. Mib-mediated Notch signaling has also been demonstrated to regulate the number of KA neurons in the p3 domain. However, the relationship between Jagged2 and Mib during late neurogenesis remains unclear. Here we investigate how Mib is involved in the regulation of Jagged2 and the long-range Notch signaling. Ubiquitination of Jagged2 by Mib was found to promote its proteasome-dependent degradation in undifferentiated P19 cells, but not in differentiated P19 cells by retinoic acid. Co-IP assay revealed that Mib physically interacts with Jagged2, but not with the intracellular domain itself. Cell transplantation experiments showed that the formation of extracellular vesicles (EVs) containing Jagged2 was promoted by the co-expression of Mib. Our observations suggest that EVs containing Jagged2 and Mib may play a role in the Notch signaling in discrete compartments of the neural tube during the development of the vertebrate nervous system.</p>","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"29 3","pages":"95-104"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12527450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-06-30DOI: 10.12717/DR.2025.29.2.31
Semi Hwang, Byeongseok Kim, Johee Kim, Yeonju Suh, Jimin Lee, Sangok Park, Ok-Hee Lee, ManRyeol Lee, Youngsok Choi
Transcriptional coactivator with PDZ-binding motif (TAZ) functions as a transcriptional coactivator, which shuttles between the cytoplasm and the nucleus under the Hippo signaling. It is known to be involved in promoting cell proliferation, organ overgrowth, survival to stress, and dedifferentiation by interacting with TEAD transcription factors (TEADs). However, the regulation of TAZ by intrauterine hormones has not yet been investigated. In this study, we investigated TAZ expression during the estrous cycle in the normal mouse uterus and the effect of estrogen and progesterone on TAZ expression in the ovariectomized (OVX) mouse uterus. TAZ expression levels did not show a statistically significant change in the uterus during the estrous cycle. However, immunofluorescence revealed that TAZ nuclear localization significantly increased at the estrus stage. In the OVX mouse uterus, the expression levels of TAZ mRNA and protein dramatically increased in a time-dependent manner after estrogen treatment. Also, immunofluorescence showed that the nuclear TAZ expression increased at 6 h and 12 h after estrogen treatment compared to the oil treated OVX mouse uterus (0 h). Finally, pretreatment of an estrogen receptor (ER) antagonist ICI 182,780 efficiently reduced estrogen-induced TAZ expression. However, progesterone did not significantly affect the expression of TAZ in both mRNA and protein levels. In conclusion, TAZ expression is regulated and activated by estrogen through nuclear estrogen receptors, ERα, and ERβ in the uterine environment.
{"title":"Regulation of Transcriptional Coactivator with PDZ-Binding Motif (TAZ) Expression by Estrogen in the Mouse Uterine Endometrium.","authors":"Semi Hwang, Byeongseok Kim, Johee Kim, Yeonju Suh, Jimin Lee, Sangok Park, Ok-Hee Lee, ManRyeol Lee, Youngsok Choi","doi":"10.12717/DR.2025.29.2.31","DOIUrl":"10.12717/DR.2025.29.2.31","url":null,"abstract":"<p><p>Transcriptional coactivator with PDZ-binding motif (TAZ) functions as a transcriptional coactivator, which shuttles between the cytoplasm and the nucleus under the Hippo signaling. It is known to be involved in promoting cell proliferation, organ overgrowth, survival to stress, and dedifferentiation by interacting with TEAD transcription factors (TEADs). However, the regulation of TAZ by intrauterine hormones has not yet been investigated. In this study, we investigated TAZ expression during the estrous cycle in the normal mouse uterus and the effect of estrogen and progesterone on TAZ expression in the ovariectomized (OVX) mouse uterus. TAZ expression levels did not show a statistically significant change in the uterus during the estrous cycle. However, immunofluorescence revealed that TAZ nuclear localization significantly increased at the estrus stage. In the OVX mouse uterus, the expression levels of TAZ mRNA and protein dramatically increased in a time-dependent manner after estrogen treatment. Also, immunofluorescence showed that the nuclear TAZ expression increased at 6 h and 12 h after estrogen treatment compared to the oil treated OVX mouse uterus (0 h). Finally, pretreatment of an estrogen receptor (ER) antagonist ICI 182,780 efficiently reduced estrogen-induced TAZ expression. However, progesterone did not significantly affect the expression of TAZ in both mRNA and protein levels. In conclusion, TAZ expression is regulated and activated by estrogen through nuclear estrogen receptors, ERα, and ERβ in the uterine environment.</p>","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"29 2","pages":"31-46"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-06-30DOI: 10.12717/DR.2025.29.2.19
HeeJi Choi, Yong-Pil Cheon
The deleted in azoospermia like (DAZL) gene is a member of the DAZ gene family. It is firstly identified in male germ cells and recognized as a key molecule of their development, now it is extended to the female germ cells and the embryo. The DAZL gene is constructed with 11 exons, 10 introns, a 5' untranslated region (UTR), and a 3' UTR, and the enhancers at the upstream of the promoter in both human and mouse. It has been revealed that DAZL gene expression is not restricted to germ cells. The known mechanisms for expression regulation include the CpG methylation on the promoter region and post-transcriptional regulation by antagonistic proteins. DAZL protein has one RNA recognition motif (RRM) and one DAZ repeat. DAZL orchestrates the translation of numerous mRNAs essential for germ cell proliferation, differentiation, and survival. Several studies have unveiled DAZL's broader roles, including its involvement in stemness and tumorigenicity through post-transcriptional regulation via polyadenylation and potential functions in RNA stabilization. The alternatively spliced variants are also evaluated in different tissues. This review consolidates current knowledge on DAZL's molecular mechanisms, expression, and emerging research directions, and introduces DAZL gene anatomy.
{"title":"Anatomy and Function of Deleted in Azoospermia Like (DAZL) Gene in Human and Mouse.","authors":"HeeJi Choi, Yong-Pil Cheon","doi":"10.12717/DR.2025.29.2.19","DOIUrl":"10.12717/DR.2025.29.2.19","url":null,"abstract":"<p><p>The deleted in azoospermia like (DAZL) gene is a member of the DAZ gene family. It is firstly identified in male germ cells and recognized as a key molecule of their development, now it is extended to the female germ cells and the embryo. The DAZL gene is constructed with 11 exons, 10 introns, a 5' untranslated region (UTR), and a 3' UTR, and the enhancers at the upstream of the promoter in both human and mouse. It has been revealed that DAZL gene expression is not restricted to germ cells. The known mechanisms for expression regulation include the CpG methylation on the promoter region and post-transcriptional regulation by antagonistic proteins. DAZL protein has one RNA recognition motif (RRM) and one DAZ repeat. DAZL orchestrates the translation of numerous mRNAs essential for germ cell proliferation, differentiation, and survival. Several studies have unveiled DAZL's broader roles, including its involvement in stemness and tumorigenicity through post-transcriptional regulation via polyadenylation and potential functions in RNA stabilization. The alternatively spliced variants are also evaluated in different tissues. This review consolidates current knowledge on DAZL's molecular mechanisms, expression, and emerging research directions, and introduces DAZL gene anatomy.</p>","PeriodicalId":72791,"journal":{"name":"Development & reproduction","volume":"29 2","pages":"19-30"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}