• Clinical and Experimental Reproductive Medicine
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• v.50 no.3
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• pp.170-176
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• 2023

Objective: Autophagy is highly active in ovariectomized mice experiencing hormone deprivation, especially in the uterine mesenchyme. Autophagy is responsible for the turnover of vasoactive factors in the uterus, which was demonstrated in anti-Müllerian hormone receptor type 2 receptor (Amhr2)-Cre-driven autophagy-related gene 7 (Atg7) knockout (Amhr-Cre/Atg7^f/f mice). In that study, we uncovered a striking difference in the amount of sequestosome 1 (SQSTM1) accumulation between virgin mice and breeder mice with the same genotype. Herein, we aimed to determine whether repeated breeding changed the composition of mesenchymal cell populations in the uterine stroma. Methods: All female mice used in this study were of the same genotype. Atg7 was deleted by Amhr2 promoter-driven Cre recombinase in the uterine stroma and myometrium, except for a triangular stromal region on the mesometrial side. Amhr-Cre/Atg7^f/f female mice were divided into two groups: virgin mice with no mating history and aged between 11 and 12 months, and breeder mice with at least 6-month breeding cycles with multiple pregnancies and aged around 12 months. The uteri were used for Western blotting and immunofluorescence staining. Results: SQSTM1 accumulation, representing Atg7 deletion and halted autophagy, was much higher in virgin mice than in breeders. Breeders showed reduced accumulation of several vasoconstrictive factors, which are potential autophagy targets, in the uterus, suggesting that the uterine stroma was repopulated with autophagy-intact cells during repeated pregnancies. Conclusion: Multiple pregnancies seem to have improved the uterine environment by replacing autophagy-deficient cells with autophagy-intact cells, providing evidence of cell mixing.

• Korean Journal of Animal Reproduction
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• v.16 no.4
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• pp.387-397
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• 1993

To examine local response of adenosie(purine nucleoside) on the developing mammary gland, Elvax 40P implants containing adenosine were surgically implanted into mammary fat pad of the five week old female ICR mice. Inguinal(the 4th) mammary glands of anesthetized mice were exposed andplaced the implants for 12 days. One gland was treated with an adenosine implant, while the contralateral gland received a blank implant as control. For whole-mount preparations, glands were stained with alum carmine, and for histological observation, micro-selected mammary glands were stained with hematoxylin and eosin Y. Implantation with Elvax 40P did not affect on the damage of neighboring mammary tissue. Adenosie 25 or 250$\mu\textrm{g}$ per slow-release implant stimulated local mammary end bud formation of ovariectomized mice such as end bud size and numbers of end bud per gland in a dose dependent manner(P<0.05), and lower concentration of adenosie(2.5 or 25$\mu\textrm{g}$/implant) increased numbers of end bud(P<0.05) and end bud size(P<0.1) of intact mice. Adenosine treatment and intact ovarian function had moderate interation effects on the stimulation of end bud formation at 2.5$\mu\textrm{g}$ adenosine/implant(P<0.1). In histological observation, adenosine implants increased numbers of mammary epithelial type of cells at mammary duct in the presence or absece ofovary. These results indicate that adenosine should be one of regulators in mouse mammary ductal growth.

• Biomedical Science Letters
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• v.16 no.4
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• pp.239-246
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• 2010

It is suggested that ovariectomy induces body weight gain primarily in the form of adipose tissue in rodents. Since liver peroxisome proliferator-activated receptor ${\alpha}$ (PPAR${\alpha}$) and uncoupling 2 (UCP2) are involved in the regulation of energy expenditure, it was investigated whether swim training regulates ovariectomy-induced adiposity and steatosis through liver PPAR${\alpha}$ and UCP2 activation in female ovariectomized mice, an animal model of postmenopausal women. Swim-trained mice had significantly decreased adipose tissue weights compared with sedentary control mice. Histological analysis showed that hepatic lipid accumulation was inhibited by swim training. Concomitantly, swim training significantly increased mRNA levels of PPAR${\alpha}$ and its target genes responsible for peroxisomal fatty acid ${\beta}$-oxidation, such as acyl-CoA oxidase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase and thiolase in the liver. Moreover, swim training induced the mRNA expression of UCP2. These results suggest that swim training can effectively prevent adiposity and steatosis caused by ovariectomy, in part through activation of liver PPAR${\alpha}$ and UCP2 in female obese mice.

• Journal of the Korean Applied Science and Technology
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• v.36 no.4
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• pp.1153-1163
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• 2019

In women, obesity rises with menopause. By comparing the dose-dopendent effects of genistein on regulation of body weight and lipid levels with swimming exercise in female ovariectomized (OVX) mice, an animal model of postmenopausal women, the effective dose of genistein on obesity control was investigated. Ovariectomized female mice were divided into control group, swimming exercise group and genistein concentration (0.005%, 0.05%, 0.1% wt/wt) treatment group and all mice fed high-fat diet for 8 weeks. The three different genistein doses as well as swimming decreased body weight, white adipose tissue mass, plasma lipid levels and lipid accumulation in liver, compared with control OVX mice. These decrease effectiveness of genistein showed dose-dependent manner, and is most effective at 0.1% genistein concentration, and paralleled effects of swimming on body weight, white adipose tissue, plasma lipid levels and lipid accumulation in liver. This present findings indicate that optimal dose of genistein in feamle OVX mice have a similar effect to swimming exercise on improvement of obesity. Intake of dietary genistein supplements will help obesity prevention in postmenopausal women.

• Journal of the Korean Applied Science and Technology
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• v.36 no.4
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• pp.1172-1180
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• 2019

It was studied whether fenofibrate alone or combinational treatments of fenofibrate and 17β-estradiol regulates serum lipid levels, and whether the effects of fenofibrate on serum lipid metabolism are affected by co-administration of 17β-estradiol in low-fat diet-fed ovariectomized female mice. Compared with low-fat diet-fed controls, mice treated with fenofibrate alone and mice treated with fenofibrate and 17β-estradiol didn't decrease body weight at 8 weeks. Fenofibrate alone or combinational treatments of fenofibrate and 17β-estradiol did not regulate serum levels of total cholesterol and HDL-cholesterol. Fenofibrate decreased plasma levels of LDL-cholesterol and triglycerides compared with controls. The combinational treatments of fenofibrate and 17β-estradiol showed more beneficial effects on triglycerides than fenofibrate alone. Therefore, the present study found that serum triglycerides reduced by fenofibtae treatment alone could be more improved by combinational treatments of fenofibrate and 17β-estradiol in low-fat diet-fed ovariectomized female mice.

• Journal of the Korean Applied Science and Technology
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• v.37 no.5
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• pp.1125-1137
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• 2020

This study investigated whether swimming exercise suppresses(: inhibites) the inflammatory response in adipose tissue in obese mice induced by a high fat diet after ovariectomy in female mice. Experimental group and control group were divided into sham-opereated group (Sham), ovariectomized group (OVX), and ovariectomized group with swimming exercise (OVX/Ex). All female mice fed high fat diet (45% fat) for 8 weeks. Compared with the Sham, the OVX increased the weight of visceral adipose tissue including parametrial, retroperitoneal, and mesenteric adipose tissue. Compared to the OVX, the OVX/Ex demonstrated reductions the weight of visceral adipose tissue. Compared to the Sham, the OVX decreased the mRNA expression of IκBα and increased the mRNA expression of inflammatory cytokines (L-6, MCP-1, TNF-α and leptin) in adipose tissue. But the OVX/Ex appeared to increase the mRNA expression of IκBα and decrease the mRNA expression of inflammatory cytokines in adipose tissue, compared with the OVX. This findings suggested that swimming exercise is useful for preventing adipose tissue inflammation, which will be effective in the prevention and treatment of obesity in obese mice induced obesity by a high fat diet after ovariectomy.

• Korean Journal of Veterinary Research
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• v.45 no.4
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• pp.545-552
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• 2005

The major protocol features of the rodent uterotrophic assay have been evaluated using a range of reference chemicals. The protocol variables considered include the selection of the test species and route of chemical administration, the age of the test animals, the maintenance diet used, and the specificity of the assay for estrogens. The rodents were ovariectomized under general anesthesia via bilateral flank incisions and randomly assigned to groups of 5 animals. Chemicals were DEHP, DBP, BPA and NP, were injected sc once daily with combinations of chemicals treatments for 3 days. In the results, the reported estrogenic chemicals DEHP and DBP were both negative in the single dose treatments. But, in the combinations of chemicals treatments, DEHP and DBP increased in bud number of mammary gland. Treatment of ovariectomized mice with combinations of other chemicals resulted in uterine and vaginal hyperplasia. The additive estrogenic effects were seen with the combinations of $17{\beta}$-Bestradiol and DBP treatment. the competitive estrogenic effects were seen with the combinations of $17{\beta}$-Bestradiol and nonylphenol, $17{\beta}$-Bestradiol and bisphenol-A treatments. These results offers a sysmatic and mechanistically informative approach to assessing estrogenicity. it provides a useful profile of activity using a reasonable amount of resources and is compatible with the study of individual chemicals as well as the investigation of interactions among combinations of chemicals. The results described illustrate the intrinsic complexity of evaluating chemicals for estrogenic activities and conform the need for rigorous attention to experimental design and criteria for assessing estrogenic activity.

• Korean Journal of Plant Resources
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• v.29 no.5
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• pp.532-538
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• 2016

Menopause is characterized by a decrease in estrogen production by the ovaries. Furthermore, the risk of developing chronic diseases including cardiovascular disease, obesity, and diabetes increases in menopausal women. In this study, we evaluated the ability of Caragana sinica (CS) to affect lipid and glucose metabolism in an ovariectomized Sprague-Dawley rat model of induced menopause. The animals were divwided randomly into three groups: sham-operated rats (SHAM), ovariectomized rats (OVX), and ovariectomized rats treated with 1% water extract of CS (OVX-CS). The OVX-CS treated mice showed a significant decrease in body weight, adipose tissue, triglyceride, and total cholesterol. Improved lipid and glucose profiles were also observed, and were attributed to suppression of hepatic lipogenesis and adipokine production and regulation of glucose-regulating enzyme activity. Therefore, these findings indicate a potential use for CS as a functional food for menopause-induced hyperlipidemia and hyperglycemia.

• Journal of Biomedical and Translational Research
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• v.19 no.4
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• pp.73-78
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• 2018

Osteoporosis is a major worldwide public health problem that poses a great economic burden to society. Puerariae Radix, the dried root of Pueraria lobata (Wild.) Ohwi, has been widely used in Asia. This study investigated the effects of Puerariae Radix (PR) on bone loss in ovariectomized (OVX) mice. C3H/HeN mice (10 weeks old) were divided into sham and OVX groups. The OVX mice were treated with vehicle, $17{\beta}-estradiol$ ($E_2$), PR (oral administration, 250 mg/kg/day) or PR (intraperitoneal administration, 50 mg/kg/every other day) for 6 weeks. Grip strength, uterus weight, serum alkaline phosphatase (ALP), estradiol concentration and osteoclast surface levels were measured. Tibiae were analyzed using microcomputed tomography. There were no significant differences in the degree of grip strength, body weight and uterine weight between OVX group and PR-treated group. As compared with the OVX group, the serum estradiol levels were significantly increased in the PR-treated group. PR (i.p.) significantly preserved trabecular bone volume, trabecular bone number, structure model index and bone mineral density of proximal tibiae metaphysic. The administration of PR lowered serum ALP and osteoclast surface levels in OVX mice, suggesting that PR can reduce the bone turnover rate in mice. The results indicate that the supply of PR can prevent OVX-induced bone loss in mice.

• BMB Reports
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• v.42 no.2
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• pp.91-95
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• 2009

Peroxisome proliferator-activated receptor $\alpha$ and estrogen are believed to be involved in metabolic changes leading to obesity. To test this relationship, we divided female wildtype and PPAR$\alpha$-deficient mice fed on a high fat diet into the following groups: mock-operated, ovariectomized (OVX), and $E_2$-treated. The visceral white adipose tissue and plasma cholesterol levels were increased significantly in wild type OVX and decreased in the $E_2$-treated group, but interestingly not in PPAR$\alpha$-deficient mice. The mRNA levels of lipoprotein lipase in adipose tissue were also increased in only wild type OVX and decreased significantly in $E_2$-treated mice. These novel results suggest the possibility of signaling crosstalk between PPAR$\alpha$ and $E_2$, causing obesity in vivo.