• Clinical and Experimental Reproductive Medicine
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• v.48 no.1
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• pp.69-79
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• 2021

Objective: Poor ovarian response (POR) refers to a subnormal follicular response that leads to a decrease in the quality and quantity of the eggs retrieved after ovarian stimulation during assisted reproductive treatment (ART). The present study investigated the associations of multiple variants of the estrogen receptor 2 (ESR2) and follicle-stimulating hormone receptor (FSHR) genes with POR in infertile Jordanian women undergoing ART. Methods: Four polymorphisms, namely ESR2 rs1256049, ESR2 rs4986938, FSHR rs6165, and FSHR rs6166, were investigated in 60 infertile Jordanian women undergoing ART (the case group) and 60 age-matched fertile women (the control group), with a mean age of 33.60±6.34 years. Single-nucleotide polymorphisms (SNPs) were detected by restriction fragment length polymorphism and then validated using Sanger sequencing. Results: The p-value of the difference between the case and control groups regarding FSHR rs6166 was very close to 0.05 (p=0.054). However, no significant differences were observed between the two groups in terms of the other three SNPs, namely ESR2 rs1256049, ESR2 rs4986938, and FSHR rs6165 (p=0.561, p=0.433, and p=0.696, respectively). Conclusion: The association between FSHR rs6166 and POR was not statistically meaningful in the present study, but the near-significant result of this experiment suggests that statistical significance might be found in a future study with a larger number of patients.

• Clinical and Experimental Reproductive Medicine
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• v.48 no.2
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• pp.163-173
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• 2021

Objective: This study aimed to characterize a validated model for predicting oocyte retrieval in controlled ovarian stimulation (COS) and to construct model-based nomograms for assistance in clinical decision-making regarding the gonadotropin protocol and dose. Methods: This observational, retrospective, cohort study included 636 women with primary unexplained infertility and a normal menstrual cycle who were attempting assisted reproductive therapy for the first time. The enrolled women were split into an index group (n=497) for model building and a validation group (n=139). The primary outcome was absolute oocyte count. The dose-response relationship was tested using modified Poisson, negative binomial, hybrid Poisson-E_max, and linear models. The validation group was similarly analyzed, and its results were compared to that of the index group. Results: The Poisson model with the log-link function demonstrated superior predictive performance and precision (Akaike information criterion, 2,704; λ=8.27; relative standard error (λ)=2.02%). The covariate analysis included women's age (p<0.001), antral follicle count (p<0.001), basal follicle-stimulating hormone level (p<0.001), gonadotropin dose (p=0.042), and protocol type (p=0.002 and p<0.001 for short and antagonist protocols, respectively). The estimates from 500 bootstrap samples were close to those of the original model. The validation group showed model assessment metrics comparable to the index model. Based on the fitted model, a static nomogram was built to improve visualization. In addition, a dynamic electronic tool was created for convenience of use. Conclusion: Based on our validated model, nomograms were constructed to help clinicians individualize the stimulation protocol and gonadotropin doses in COS cycles.

• Journal of Animal Reproduction and Biotechnology
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• v.37 no.3
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• pp.155-161
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• 2022

Pregnancy-associated plasma protein-A (PAPP-A) is known as an important biomarker for fetal abnormality during first trimester and has a pivotal role in follicle development and corpus luteum formation. And also, it is being revealed that an expression of PAPP-A in various cells and tissues such as cancer and lesion area. PAPP-A is the major IGF binding protein-4 (IGFBP-4) protease. Cleavage of IGFBP-4 results in loss of binding affinity for IGF, causing increased IGF bioavailability for proliferation, survival, and migration. Additionally, PAPP-A can be used as a promising therapeutic target for healthy longevity. Despite growing interest, almost nothing is known about how PAPP-A expression is regulated in any tissue. This review will focus on what is currently known about the zinc metalloproteinase, PAPP-A, and its role in cells and tissues. PAPP-A is expressed in proliferating cells such as fetus in uterus, granulosa cells in follicle, dermis in wound, cancer cells, and Sertoli cells in testis. They have common characteristics of proliferation faster than normal cells with stimulating IGFs action and inhibiting IGFBPs. The PAPP-A functions and expression studies in livestock have not yet been conducted much. Further studies are needed to use PAPP-A as a marker for healthy longevity in animal science.

• Animal Bioscience
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• v.35 no.11
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• pp.1744-1751
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• 2022

Objective: The present study aimed to investigate the effect of xylo-oligosaccharides (XOS) administration on egg production, reproductive hormones, serum lipids and adipokines of hens at the late cycle of reproduction. Methods: Four treatments included control (basal diet) and XOS addition at 2.0 (XOS-2), 4.0 (XOS-4), or 6.0 (XOS-6) g/kg of diet using 288 commercial Hy-Line brown hens from 73 to 84 wk of age. Egg production, body fat deposition, reproductive tract and hormones, lipid metabolism and adipokines were determined. Results: At 84 wk, compared to the control, XOS supplementation at the three doses increased (p<0.001) egg-laying rates by 13.2% averagely, which led to a higher egg mass by 131 g/hen throughout the whole trial period. Abdominal fat and skinfold of XOS treatments were decreased (p<0.001) by 26.1% and 18.6%, respectively; large follicles and ovary weight were increased (p<0.001) by 0.73 follicle/hen and 18.6%, respectively. For serum parameters, cholesterol and triglyceride were decreased (p<0.001) by 17.5% and 29.2%, respectively; luteinizing hormone, follicle-stimulating hormone, and progesterone were increased (p≤0.001) by 16%, 31%, 29%, respectively; adiponectin and visfatin were increased (p<0.001) by 34% and 44%, respectively; but chemerin and leptin were decreased (p≤0.001) by 22% and 14%, respectively. With the increased XOS doses, linear decreases (p<0.05) were found on abdominal skinfold and serum triglyceride. Conclusion: The obtained data indicate that XOS can be used as an additive to improve fecundity by beneficially modulating fat deposition, lipid metabolism, reproductive hormones, and adipokines of hens at the late cycle of reproduction.

• Clinical and Experimental Reproductive Medicine
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• v.49 no.3
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• pp.175-184
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• 2022

Objective: The aim of this study was to evaluate the impacts of platelet-rich plasma (PRP) and conditioned medium (CM) derived from endometrial stromal cells on mouse preantral follicle culture in a two-dimensional system to produce competent mature oocytes for fertilization. Methods: In total, 240 preantral follicles were isolated from female mouse ovarian tissue and divided into four groups. The preantral follicles were isolated three times for each group and then cultured, respectively, in the presence of alpha minimum essential medium (control), PRP, CM, and PRP+CM. The in vitro growth, in vitro maturation, and cleavage percentage of the preantral follicles were investigated. Immunocytochemistry (IHC) was also conducted to monitor the meiotic progression of the oocytes. Additionally, the mRNA expression levels of the two folliculogenesis-related genes (Gdf9 and Bmp15) and two apoptosis-related genes (Bcl2 and Bax) were investigated using real-time polymerase chain reaction. Results: In the PRP, CM, and PRP+CM groups, the preantral follicle maturation (evaluated by identifying polar bodies) were greater than the control group. The cleavage rate in the CM, and PRP+CM groups were also greater than the control group. IHC analysis demonstrated that in each treatment group, meiotic spindle was normal. In the PRP+CM group, the gene expression levels of Bmp15, Gdf9, and Bcl2 were greater than in the other groups. The Bax gene was more strongly expressed in the PRP and control groups than in the other groups. Conclusion: Overall, the present study suggests that the combination of CM and PRP can effectively increase the growth and cleavage rate of mouse preantral follicles in vitro.

• The Korea Journal of Herbology
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• v.34 no.6
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• pp.139-146
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• 2019

Objective : Recently, hair has become one of the important aspects of beauty. So, there are many studies about prevention and treatment of alopecia. Finasteride and minoxidil have been known to drug for alopecia treatment. However, these agents have side effects such as irritation, pruritus, and erythema when they were used for a long time. So, we assessed hair growth effect on herbal mixture (RAA) include in Rehmanniae Radix Preparata, Achyranthis Radix, and Acanthopanacis Cortex. Methods : 6 weeks aged C57BL/6 mice were divided three treatment groups. : CON group (vehicle solution), MNXD group (positive control, 3% minoxidil), RAA group (15% RAA solution). And we applied 200 ㎕ of three groups to shaved dorsal skin every day. Hair growth effects of treatment were determined through phototrichogram by folliscope and hair follicle morphometry by H&E staining. And we assessed hair growth-related gene (VEGF, IGF-1, TGF-β1) expressions by western blot and 5-α reductase II analysis of dermal (skin) or internal organ (prostate gland). Results : Hair density and hair follicle size in MNXD or RAA group was enhanced compared to those of CON group, respectively. Also, the protein expression levels in dermal of VEGF, IGF-1 increased but TGF-β1 decreased in RAA and MNXD group, compared to CON group, respectively. 5-α reductase II levels of tissues in MNXD or RAA group significantly decreased compared to those of CON group, respectively. Conclusion : These results suggest that RAA has the promoting effect on hair growth.

• Clinical and Experimental Reproductive Medicine
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• v.50 no.1
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• pp.34-43
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• 2023

Objective: The aim of this study was to investigate the effect of royal jelly (RJ), a powerful natural antioxidant, on cyclophosphamide-induced ovarian damage. Methods: Thirty-two Wistar albino rats were divided into four groups. Oral treatment was administered to all rats for 16 days after a single intraperitoneal injection. The control group received intraperitoneal and oral saline; the RJ group received intraperitoneal saline and 100 mg/kg/day oral RJ; the cyclophosphamide group received intraperitoneal 100 mg/kg cyclophosphamide and oral saline; and the treatment group received intraperitoneal 100 mg/kg cyclophosphamide and 100 mg/kg/day oral RJ. The groups were compared in terms of ovarian reserve tests and histopathological changes in the ovary and uterus. Results: All follicle counts were higher in the treatment group than in the cyclophosphamide group. The increase in the number of preantral follicles (p=0.001) and the decrease in the number of atretic follicles (p=0.004) were statistically significant. RJ treatment significantly improved follicular degeneration and cortical fibrosis in the ovary and epithelial and gland degeneration in the uterus due to cyclophosphamide toxicity. Conclusion: According to these results, RJ reduces cyclophosphamide-related ovarian and endometrial damage in rats. For this reason, it should be further investigated to determine its effects on reproductive function.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.440-447
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• 2023

Background: The human hair follicle undergoes cyclic phases-anagen, catagen, and telogen-throughout its lifetime. This cyclic transition has been studied as a target for treating hair loss. Recently, correlation between the inhibition of autophagy and acceleration of the catagen phase in human hair follicles was investigated. However, the role of autophagy in human dermal papilla cells (hDPCs), which is involved in the development and growth of hair follicles, is not known. We hypothesized that acceleration of hair catagen phase upon inhibition of autophagy is due to the downregulation of Wnt/β-catenin signaling in hDPCs, and that components of Panax ginseng extract can increase the autophagic flux in hDPCs. Methods: We generated an autophagy-inhibited condition using 3-methyladenine (3-MA), a specific autophagy inhibitor, and investigated the regulation of Wnt/β-catenin signaling using the luciferase reporter assay, qRT-PCR, and western blot analysis. In addition, cells were cotreated with ginsenoside Re and 3-MA and their roles in inhibiting autophagosome formation were investigated. Results: We found that the unstimulated anagen phase dermal papilla region expressed the autophagy marker, LC3. Transcription of Wnt-related genes and nuclear translocation of β-catenin were reduced after treatment of hDPCs with 3-MA. In addition, treatment with the combination of ginsenoside Re and 3-MA changed the Wnt activity and hair cycle by restoring autophagy. Conclusions: Our results suggest that autophagy inhibition in hDPCs accelerates the catagen phase by downregulating Wnt/β-catenin signaling. Furthermore, ginsenoside Re, which increased autophagy in hDPCs, could be useful for reducing hair loss caused by abnormal inhibition of autophagy.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.2
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• pp.167-176
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• 2023

This study aims to explore the impact of Rehmannioside D (RD) on ovarian functions of rats with diminished ovarian reserve (DOR) and its underlying mechanisms of action. A single injection of cyclophosphamide was performed to establish a DOR rat model, and fourteen days after the injection, the rats were intragastrically administrated with RD for two weeks. Rat estrus cycles were tested using vaginal smears. Ovarian tissues were histologically evaluated, the number of primordial, mature, and atretic follicles was calculated, and the apoptotic rate of granulosa cells. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E₂) levels were determined by ELISA assays. Protein levels of Forkhead Box O1 (FOXO1), KLOTHO, Bcl-2, and Bax were investigated in ovarian tissues of DOR rats. The binding between FOXO1 and KLOTHO was verified by ChIP assay. High-dose administration of RD into DOR rats improved their estrus cycles, increased ovarian index, enhanced the number of primordial and mature follicles, reduced the number of atretic follicle number, and ovarian granulosa cell apoptosis in addition to inhibiting FSH and LH levels and upregulating E₂ expression. FOXO1 and KLOTHO were significantly suppressed in DOR rats. FOXO1 knockdown partially suppressed the protective effects of RD on DOR rats, and KLOTHO overexpression could restore RD-induced blockade of DOR development despite knocking down FOXO1. FOXO1 antibody enriched KLOTHO promoter, and the binding between them was reduced in DOR group compared to that in sham group. RD improved ovarian functions in DOR rats and diminished granulosa cell apoptosis via the FOXO1/KLOTHO axis.

• The Korea Journal of Herbology
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• v.39 no.1
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• pp.23-29
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• 2024

Objectives : Polyporus umbellatus is a medicinal mushroom that has been used for over thousands years in Chinese medicine as a powerful diuretic to relieve fluid retention and edema. Dermal papilla is located at the bottom of the hair follicle and connected to the blood vessels where it gets the nutrients and oxygen to nurture hair follicle. This study examined the mechanism through which the ethanol extract of Polyporus umbellatus (EPU) promoted the proliferation of human dermal papilla cells (HHDPCs). Methods : To estimate the proliferative effects of EPU on HHDPCs, cell viability was estimated by thiazolyl blue tetrazolium bromide (MTT) assay. Western blotting was used to investgate the activation of ERK, phosphoinositide 3-kinase (PI3K)/Akt, β-catenin, GSK-3β and heme oxygenase-1 (HO-1). Cells were treated with inhibitors of ERK and Akt prior to EPU treatment. Results : EPU promoted the proliferation of HHDPCs and the phosphorylation of ERK and Akt in dose dependent manner. However, the proliferative effect of EPU on HHDPCs was inhibited by pre-treatment of ERK inhibitor (PD98059) and Akt inhibitor (LY294002). Furthermore, EPU respectively stimulated the protein expression of β-catenin and phosphorylated GSK-3β. EPU significantly increased the protein expression levels of proliferation and cytoprotection related genes such as Bcl-2, SIRT-1, and HO-1 in cells. Conclusion : This results suggest that EPU promoted the proliferation of HHDPCs via activating PI3K/Akt and Wnt/β-catenin signaling pathway in HHDPCs.