CN116400082A - 检测ApoC3蛋白含量的试剂在制备预测卵母细胞发育试剂中的应用 - Google Patents
检测ApoC3蛋白含量的试剂在制备预测卵母细胞发育试剂中的应用 Download PDFInfo
- Publication number
- CN116400082A CN116400082A CN202310052146.XA CN202310052146A CN116400082A CN 116400082 A CN116400082 A CN 116400082A CN 202310052146 A CN202310052146 A CN 202310052146A CN 116400082 A CN116400082 A CN 116400082A
- Authority
- CN
- China
- Prior art keywords
- apoc3
- reagent
- predicting
- development
- pcos
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003153 chemical reaction reagent Substances 0.000 title claims abstract description 20
- 230000008182 oocyte development Effects 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims description 5
- 230000002611 ovarian Effects 0.000 claims abstract description 31
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 17
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 16
- 239000000090 biomarker Substances 0.000 claims abstract description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000011161 development Methods 0.000 abstract description 8
- 230000018109 developmental process Effects 0.000 abstract description 8
- 230000007423 decrease Effects 0.000 abstract 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 31
- 210000001519 tissue Anatomy 0.000 description 29
- 241000699670 Mus sp. Species 0.000 description 18
- 210000000287 oocyte Anatomy 0.000 description 13
- 210000001672 ovary Anatomy 0.000 description 13
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 13
- 206010022489 Insulin Resistance Diseases 0.000 description 12
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 10
- 238000011532 immunohistochemical staining Methods 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 102000004877 Insulin Human genes 0.000 description 5
- 108090001061 Insulin Proteins 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 229940125396 insulin Drugs 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 238000000465 moulding Methods 0.000 description 5
- 241000283707 Capra Species 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 229960002725 isoflurane Drugs 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 239000006180 TBST buffer Substances 0.000 description 3
- 239000003098 androgen Substances 0.000 description 3
- 238000002224 dissection Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 230000004153 glucose metabolism Effects 0.000 description 3
- 238000003125 immunofluorescent labeling Methods 0.000 description 3
- 230000002055 immunohistochemical effect Effects 0.000 description 3
- 230000037356 lipid metabolism Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 108010071619 Apolipoproteins Proteins 0.000 description 2
- 102000007592 Apolipoproteins Human genes 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 238000011740 C57BL/6 mouse Methods 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 206010015719 Exsanguination Diseases 0.000 description 2
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 2
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 102000009151 Luteinizing Hormone Human genes 0.000 description 2
- 108010073521 Luteinizing Hormone Proteins 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 238000011529 RT qPCR Methods 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 description 2
- 201000002893 dermoid cyst of ovary Diseases 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000013401 experimental design Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000002503 granulosa cell Anatomy 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 238000002357 laparoscopic surgery Methods 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 229940040129 luteinizing hormone Drugs 0.000 description 2
- 230000021121 meiosis Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000003470 mitochondria Anatomy 0.000 description 2
- 230000002297 mitogenic effect Effects 0.000 description 2
- 208000004971 ovarian teratoma Diseases 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 210000002027 skeletal muscle Anatomy 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 1
- 208000004611 Abdominal Obesity Diseases 0.000 description 1
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- 239000012110 Alexa Fluor 594 Substances 0.000 description 1
- 201000000736 Amenorrhea Diseases 0.000 description 1
- 206010001928 Amenorrhoea Diseases 0.000 description 1
- 206010002659 Anovulatory cycle Diseases 0.000 description 1
- 108010005853 Anti-Mullerian Hormone Proteins 0.000 description 1
- 108010056301 Apolipoprotein C-III Proteins 0.000 description 1
- 102100030970 Apolipoprotein C-III Human genes 0.000 description 1
- 206010065941 Central obesity Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 208000014311 Cushing syndrome Diseases 0.000 description 1
- FMGSKLZLMKYGDP-UHFFFAOYSA-N Dehydroepiandrosterone Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CC=C21 FMGSKLZLMKYGDP-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 206010065789 Fallopian tube obstruction Diseases 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 101710088172 HTH-type transcriptional regulator RipA Proteins 0.000 description 1
- 101000830411 Homo sapiens Probable ATP-dependent RNA helicase DDX4 Proteins 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 102100030173 Muellerian-inhibiting factor Human genes 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 108700020962 Peroxidase Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 208000002500 Primary Ovarian Insufficiency Diseases 0.000 description 1
- 102100024770 Probable ATP-dependent RNA helicase DDX4 Human genes 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000001780 adrenocortical effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 231100000540 amenorrhea Toxicity 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000868 anti-mullerian hormone Substances 0.000 description 1
- 230000002513 anti-ovulatory effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- IRUJZVNXZWPBMU-UHFFFAOYSA-N cartap Chemical compound NC(=O)SCC(N(C)C)CSC(N)=O IRUJZVNXZWPBMU-UHFFFAOYSA-N 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000010219 correlation analysis Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 230000004129 fatty acid metabolism Effects 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 230000008217 follicular development Effects 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 150000002303 glucose derivatives Chemical class 0.000 description 1
- 230000014101 glucose homeostasis Effects 0.000 description 1
- 208000018914 glucose metabolism disease Diseases 0.000 description 1
- 230000006377 glucose transport Effects 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 208000030843 hydrosalpinx Diseases 0.000 description 1
- 201000010066 hyperandrogenism Diseases 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000010832 independent-sample T-test Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 210000002570 interstitial cell Anatomy 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000004130 lipolysis Effects 0.000 description 1
- 230000008604 lipoprotein metabolism Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000002175 menstrual effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 238000009806 oophorectomy Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000000624 ovulatory effect Effects 0.000 description 1
- 210000004681 ovum Anatomy 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000003836 peripheral circulation Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 229960002847 prasterone Drugs 0.000 description 1
- 206010036601 premature menopause Diseases 0.000 description 1
- 208000017942 premature ovarian failure 1 Diseases 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000010814 radioimmunoprecipitation assay Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 210000000801 secondary oocyte Anatomy 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 230000006016 thyroid dysfunction Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 230000006496 vascular abnormality Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/775—Apolipopeptides
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
本发明公开了检测ApoC3蛋白含量的试剂在制备预测卵母细胞发育试剂中的应用。本发明发现在卵巢组织中ApoC3表达在小鼠发育过程中逐渐升高，在第21日龄达到高峰，随后缓慢下降。因此，ApoC3可作为预测卵母细胞发育的生物学标志物，用于预测卵母细胞发育情况。
Description
技术领域
本发明属于医药领域，具体涉及检测ApoC3蛋白含量的试剂在制备预测卵母细胞发育试剂中的应用。
背景技术
血清载脂蛋白C(apolipoprotein C，ApoC)是载脂蛋白家族中的一员。ApoC中，以ApoC3浓度最高，其对稳定脂蛋白结构、结合和转运脂质、调节脂蛋白代谢都有重要作用。ApoC3最初在肝脏和小肠中合成，其基因位于第11号染色体长臂11q23.3，长约3.1kb，有4个外显子和3个内含子，是含有79个氨基酸的肽链，大小为8.8kDa的小分子糖蛋白。ApoC3在血液中含量最高，主要调节富含甘油三酯脂蛋白(triglyceride-rich lipoproteins，TRLs)的分解与代谢。
①ApoC3与脂代谢：ApoC3在降低血脂方面取得了许多临床与基础研究，已被确定为新的降脂靶点。ApoC3被普遍认为是心血管疾病的直接危险因素。目前，已有相关研究将外周循环中ApoC3水平与动脉粥样硬化以及不良心血管结局联系起来。ApoC3对于调节脂肪酸代谢十分重要，卵巢局部脂质代谢为卵母细胞减数分裂的恢复提供了一种强有力的能量来源。卵母细胞中的脂质脂解产生的脂肪酸通过线粒体中的β-氧化进一步代谢以产生ATP，供卵母细胞成熟并保证其质量。PCOS患者脂代谢异常，卵母细胞中脂质沉积过多会增加活性氧的含量并且破坏线粒体和内质网的功能，最终使卵母细胞的发育受阻。
②ApoC3与糖代谢：ApoC3与葡萄糖代谢也有密切关系。血浆中ApoC3浓度升高，可加重胰岛素抵抗以及糖尿病的发展。在一项针对2型糖尿病受试者的小型研究中发现，抑制ApoC3可改善全身胰岛素抵抗(IR)。ApoC3可能通过促进胰岛细胞凋亡和葡萄糖稳态紊乱参与IR的病理生理过程。已有文献在肾病、系统性红斑狼疮、糖尿病及肝病等病理状态下报道ApoC3对血糖的损害。PCOS患者的糖代谢紊乱会引起卵巢局部内环境中的葡萄糖代谢物水平的变化。卵子的发育过程需要葡萄糖提供能量，而PCOS患者由于卵巢存在局部胰岛素抵抗状态、葡萄糖转运途径缺陷，导致葡萄糖的利用率降低，不利干卵母细胞的生长发育。
③ApoC3与炎症反应：ApoC3促进促炎核因子kappa B(NF-κB)信号转导，进而激活单核细胞，促进局部巨噬细胞募集和炎症发生。ApoC3还可诱导活性氧介导的血管平滑肌增殖，加期动脉粥样硬化的进程。Kelly等学者在2001年首次提出PCOS患者处于慢性低度炎症状态，并且与IR和腹部肥胖有关。肥胖可能加重PCOS患者的炎症状态，并增加远期心血管疾病的发病风险。PCOS脂代谢紊乱患者血清中有更高水平的ApoC3，ApoC3的升高可能通过激活内皮细胞蛋白激酶(PKC-β)和骨骼肌细胞外信号调节激酶(ERK1/2)，诱导炎症反应，促进炎症因子：肿瘤坏死因子(TNF-α)、核因子(NF-κB)进一步加重PCOS胰岛素抵抗、脂质异常的发生。
④PCOS患者存在卵巢局部IR，与高表达的ApoC3密切相关，导致排卵功能障碍。多项研究表明在患有PCOS的女性中，胰岛素活性在经典靶器官(脂肪组织和骨骼肌等)中缺失引起胰岛素抵抗。PCOS同时具有卵巢局部胰岛素抵抗，影响卵巢局部葡萄糖代谢、胆固醇摄取、甾体激素生成以及细胞分裂增殖。有研究发现PCOS患者卵巢颗粒细胞存在受体后胰岛素信号传导分子的改变，导致下游激酶活性的改变，减弱胰岛素信号转导，促进卵巢局部胰岛素抵抗发生。胰岛素在细胞内的信号传导途径包括调节葡萄糖代谢的促代谢途径和引起细胞分裂增殖作用的促分裂途径等。卵巢局部IR时表现为细胞内胰岛素的促代谢作用途径受损，而促分裂作用途径发生放大现象，使卵巢体积增加、卵泡发育停滞、排卵障碍、及卵巢局部高雄激素状态。
发明内容
本发明的目的是提供检测ApoC3蛋白含量的试剂在制备预测卵母细胞发育试剂中的应用。
本发明前期对PCOS患者卵巢组织进行免疫组化研究：发现PCOS患者卵巢组织中ApoC3蛋白高表达。进一步通过对PCOS小鼠和正常对照小鼠卵巢组织行免疫组化和免疫荧光定位检查，发现：ApoC3定位于小鼠卵母细胞胞浆内，我们推测ApoC3表达与卵母细胞发育相关。我们随后采用出生后7至42日龄的小鼠进行验证，小鼠出生第7至42日，是卵巢的发育阶段。我们研究发现：ApoC3在小鼠不同发育时期表达水平不同，ApoC3表达在小鼠卵泡发育过程中逐渐升高，在卵巢组织中第21日龄达到高峰，随后缓慢下降。第21日即小鼠青春期启动期，此时期卵母细胞接受促性腺激素刺激(黄体生成素LH)，从初期卵母细胞第一次减数分裂前期发展为次级卵母细胞的关键时间窗可作为预测卵母细胞发育的生物学标志物。
因此，本发明的第一个目的是提供检测ApoC3蛋白含量的试剂在制备预测卵母细胞发育试剂中的应用。
优选，是检测卵巢组织中的ApoC3蛋白含量的试剂在制备预测卵母细胞发育试剂中的应用。
本发明的第二个目的是提供ApoC3蛋白作为预测卵母细胞发育的生物学标志物的应用。
本发明的第三目的是提供一种预测卵母细胞发育试剂，其包括检测ApoC3蛋白含量的试剂。
本发明发现ApoC3表达在小鼠发育过程中逐渐升高，在第21日龄达到高峰，随后缓慢下降。因此，ApoC3可作为预测卵母细胞发育的生物学标志物，用于预测卵母细胞发育情况。
附图说明：
图1是PCOS患者和对照组卵巢组织免疫组化染色。棕黄色染色为ApoC3阳性面积。(A)对照组和PCOS组免疫组化染色；(B)两组免疫组化ApoC3阳性面积分析。
图2是PCOS小鼠和对照小鼠在造模不同阶段卵巢组织的ApoC3蛋白表达水平。(A)两组小鼠在三个造模阶段：造模第一周(1W)，造模第二周(2W)，造模第三周(3W)的ApoC3蛋白表达水平。(B)不同是造模阶段ApoC3相对蛋白表达量。
图3是PCOS小鼠和对照小鼠在造模不同阶段卵巢组织的ApoC3表达及定位。(A)卵巢组织中ApoC3的免疫组化染色。棕黄色染色为ApoC3阳性区域，红色箭头所示为卵母细胞。比例尺:200μm；50μm。(B)卵巢组织中ApoC3免疫荧光染色。ApoC3呈红色染色；细胞核呈蓝色染色。白色箭头所示为卵母细胞。比例尺:100μm；75μm。(C)免疫组化染色分析的ApoC3阳性区域。(D)免疫荧光染色分析ApoC3染色阳性区域。
图4是ApoC3在卵巢组织中的动态表达情况。(A)第7至42日龄小鼠卵巢组织免疫组化染色，棕色染色的为ApoC3阳性区域，红色箭头指示为卵母细胞；比例尺＝200μm；50μm。(B)免疫组化染色分析ApoC3阳性区域。
图5是实验设计图。
具体实施方式：
以下实施例是对本发明的进一步说明，而不是对本发明的限制。
实施例1：
一、研究方法
1.临床样本
收集2014年至2016年就诊于广东省妇幼保健院妇科的30名PCOS患者作为PCOS组，年龄(28.66±1.23)岁，行腹腔镜下卵巢楔形切除术，取楔形切除的小部分卵巢组织进行研究。同期收集30名年龄和体重与PCOS组匹配的非PCOS患者，因单侧卵巢畸胎瘤行腹腔镜手术患者为对照组，年龄(28.56±1.15)岁。对照组行腹腔镜下患侧卵巢畸胎瘤剔除术及健侧卵巢组织剖探术，取剖视活检的健侧卵巢组织进行研究。PCOS组及对照组病例来源于广东省妇幼保健院。腹腔镜手术收集卵巢组织样本时，其大小应达到整个卵巢组织的十分之一，在卵巢组织表面取一块类似金字塔样结构的组织，该组织应包括有颗粒细胞、卵泡膜细胞、卵母细胞、间质细胞等各种结构。手术由广东省妇幼保健院具有IV类腹腔镜执业资格的妇科内分泌主任医师进行，以确保临床样本收集的准确性及代表性。收集样本前，患者已签署手术同意书。样本采集征得患者知情同意和广东省妇幼保健院伦理委员会批准后实施(伦理审批号：201401011)。
纳入标准：(1)PCOS组为接受腹腔镜治疗，并且符合2003鹿特丹诊断标准诊断为PCOS的患者；(2)对照组为同期就诊的年龄相匹配，月经规律，临床及生化检查排除高雄激素血症。其中，因输卵管不通畅就诊患者30例。
排除标准:(1)其他高雄激素疾病如先天性肾上腺皮质增生、库欣综合征、分泌雄激素的肿瘤等；(2)其他引起排卵障碍疾病如高催乳素血症、卵巢早衰或下丘脑性闭经及甲状腺功能异常；(3)原发性高血压、1型糖尿病等血管异常性疾病；(4)卵巢肿瘤放疗或化疗史。
2.实验动物
2.1第一部分
所有C57BL/6小鼠(21日龄小鼠)购自广东斯嘉景达生物技术有限公司(许可证号:SCXK(粤)2020-0052)。将21日龄小鼠(9～13g)随机分为2组(每组n＝18):对照组(C)，PCOS组(P)。PCOS小鼠每日皮下注射脱氢表雄酮(DHEA，6mg/100g体重)溶解于芝麻油21天，对照组皮下注射芝麻油21天。动物置于温度湿度控制的房间(22±1℃，湿度45～60％)，一套12h的明暗循环。饲养于广州中医药大学(广州)国际中医药转化研究所SPF动物实验室(许可证号:SYXK(GZ)2019-0144)动物设施中。动物实验经广州中医药大学动物护理与使用专业委员会(No.20220504)批准，按照伦理标准和国家指南进行。所有小鼠均用3％异氟醚(ISO)麻醉，并在解剖前放血安乐死。
2.1.1 ELISA检测
EDTA采血管眼眶穿刺采集血样，3000转离心15分钟，-80℃保存上清，待生化和激素分析。酶联免疫检测试剂盒：血清载脂蛋白C3(SEB890Mu；云克隆公司，德克萨斯州，美国)，黄体生成素(H206-1-2；南京建成生物工程研究所，中国南京)，anti-Müllerian激素(CEA228Mu；Cloud-Clone公司，德克萨斯州，美国)，分光光度计(VL0000D0；ThermoFisher，新加坡)根据制造商的说明使用。
2.1.2 HE染色
用PBS冰上清洗卵巢两次，然后将一侧卵巢用4％多聚甲醛固定24小时。石蜡包埋组织采用梯度乙醇脱水、二甲苯透化、石蜡包埋的顺序进行。切片厚度3μm(CM1850；Leica，Nussloch，德国)，在二甲苯中脱蜡，用梯度乙醇水化，然后用苏木精和伊红染料染色，用中性树脂封片。在显微镜下观察卵泡形态和数量(DM750，Leica，Wetzlar，Germany)。
2.1.3 RNA提取和qRT-PCR
总RNA从卵巢中分离，用TRIzol试剂提取RNA(15596026；Invitrogen，卡尔斯巴德，加州)。使用RevertAidcDNA合成试剂盒反转录(K1622；美国ThermoFisher)。通过实时PCR系统(Applied Biosystems，CA，USA)监测SYBR绿色荧光的增加，进行定量实时PCR。引物序列从PrimerBank(https://pga，mgh，harvard，edu/primerbank/)获得，由Invitrogen公司合成。引物序列如下:
每个样本扩增三次。数据采用ΔΔCt方法进行相对定量分析。
2.1.4免疫组化染色
按上述方法脱蜡。采用pH为6.0的柠檬酸钠缓冲液在微波中进行抗原修复，100℃，20min，用3％的H2O2淬灭内源性过氧化物酶。正常山羊血清在室温下封闭10分钟，用一抗ApoC3(Novusbio；NB600-610，1:1000；GB112005；Servicebio，武汉，1:300)在4℃孵育2h。生物素标记山羊抗兔IgG抗体(CW2069S；切片中加入CWBio，江苏，中国)，室温孵育2h。PBS冲洗后，加入链霉亲和素-HRP，最后用DAB混合液进行显色反应。
2.1.5免疫荧光染色
小鼠卵巢组织石蜡包埋、切片、脱蜡、抗原修复及封闭按上述免疫组化染色方法进行。一抗(ApoC3,Servicebio，GB112005,1:300；DDX4,abcam，ab180462,1:50)在4℃孵育12h，PBS洗3次，Alexa Fluor 594偶联山羊抗兔和Alexa Fluor 488偶联山羊抗小鼠IgG二抗(Jackson ImmunoResearch)室温避光孵育1h。用含DAPI抗荧光淬灭封片液(P0131，碧云天，上海)室温避光染核并封片。
2.1.6蛋白印迹
小鼠卵巢组织加入RIPA裂解液(9806，CST，Beverly,Massachusetts，USA)冷冻匀浆、裂解，冷冻离心14000g，10分钟。上清液用BCA(P0012，碧云天，上海)检测蛋白总浓度，上样量为30μg。SDS-PAGE电泳条件55V 30min，120V 60min，转膜，条件300mA 45min，室温封闭2h，TBST洗3次。PVDF膜放入装有内参GAPDH(sc-47724；Santa,USA，1∶2000)和一抗ApoC3抗体(GB112005，Servicebio，武汉，1：1000)的抗体孵育盒中，4℃孵育过夜，复温、TBST洗3次，二抗为抗兔IgG-HRP和抗鼠IgG-HRP(CST，1∶10000)室温孵育1h，TBST洗3次，ECL化学发光采集图像。
2.1.7统计学方法
两组比较采用独立样本t检验。用pearson相关系数(R)进行相关性分析，用ImageJ软件进行灰度值分析。采用SPSS 25和GraphPad Prism 7进行统计计算。P<0.05被认为有统计学意义。
2.2实验部分2
2.2.1所有C57BL/6小鼠(出生7-42日龄小鼠)购自广东斯嘉景达生物技术有限公司(许可证号:SCXK(粤)2020-0052)。动物实验经广州中医药大学动物护理与使用专业委员会(No.20220719)批准，按照伦理标准和国家指南进行。每7日观察小鼠卵巢组织ApoC3的变化。所有小鼠均用3％异氟醚(ISO)麻醉，并在解剖前放血安乐死。实验设计如图5(出生后日龄：day of post partum，dpp)。
2.2.2ELISA检测
同上
2.2.3免疫组化染色
同上
2.2.4统计学方法
同上
四、研究结果
1、PCOS组患者卵巢组织和ApoC3的平均光密度明显高于对照组人群(图1)。
2、PCOS小鼠卵巢组织的ApoC3蛋白表达在造模第二周后，较对照组明显升高(图2)。
3、ApoC3主要定位在卵母细胞的细胞浆内(图3A红色箭头，图3B白色箭头标注为卵母细胞)，且同样在造模第二周后PCOS组ApoC3卵巢较对照组明显升高，ApoC3在PCOS组造模第三周后升高更为显著(图3C、D)。
4、在卵巢组织中，ApoC3表达在小鼠发育过程中逐渐升高，在卵巢组织中ApoC3表达第21日龄达到高峰，随后缓慢下降(图4)。
Claims (4)
1.检测ApoC3蛋白含量的试剂在制备预测卵母细胞发育试剂中的应用。
2.根据权利要求1所述的应用，其特征在于，是检测卵巢组织中的ApoC3蛋白含量的试剂在制备预测卵母细胞发育试剂中的应用。
3.ApoC3蛋白作为预测卵母细胞发育的生物学标志物的应用。
4.一种预测卵母细胞发育试剂，其特征在于，包括检测ApoC3蛋白含量的试剂。
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310052146.XA CN116400082A (zh) | 2023-02-02 | 2023-02-02 | 检测ApoC3蛋白含量的试剂在制备预测卵母细胞发育试剂中的应用 |
| PCT/CN2023/099895 WO2023241565A1 (zh) | 2023-02-02 | 2023-06-13 | 检测ApoC3蛋白含量的试剂在制备预测卵母细胞发育试剂中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310052146.XA CN116400082A (zh) | 2023-02-02 | 2023-02-02 | 检测ApoC3蛋白含量的试剂在制备预测卵母细胞发育试剂中的应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116400082A true CN116400082A (zh) | 2023-07-07 |
Family
ID=87018579
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310052146.XA Pending CN116400082A (zh) | 2023-02-02 | 2023-02-02 | 检测ApoC3蛋白含量的试剂在制备预测卵母细胞发育试剂中的应用 |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN116400082A (zh) |
| WO (1) | WO2023241565A1 (zh) |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7572601B2 (en) * | 2004-10-15 | 2009-08-11 | Northwestern University | Compositions and methods for determining oocyte development potential |
| US20100055730A1 (en) * | 2006-05-05 | 2010-03-04 | Anny Usheva-Simidjiyska | Methods for the Diagnosis and Treatment of Female Infertility Using Molecular Markers |
| CN105699656B (zh) * | 2016-01-25 | 2017-12-19 | 李荔 | 检测ApoC3蛋白含量的试剂在制备诊断和预测胰岛素抵抗型PCOS的试剂盒中的应用 |
| WO2021167841A1 (en) * | 2020-02-18 | 2021-08-26 | Alnylam Pharmaceuticals, Inc. | Apolipoprotein c3 (apoc3) irna compositions and methods of use thereof |
| KR102316507B1 (ko) * | 2020-02-28 | 2021-10-22 | 차의과학대학교 산학협력단 | 난소 예비력 바이오마커 및 이의 용도 |
| CN113577047A (zh) * | 2021-02-22 | 2021-11-02 | 广东省妇幼保健院 | 调控ApoC3表达量的制剂在制备预防或治疗胰岛素抵抗型多囊卵巢综合征药物中的应用 |
| CN115128277A (zh) * | 2022-05-18 | 2022-09-30 | 深圳中山泌尿外科医院 | 一组用于评估pcos卵母细胞质量的生物标志物、应用及筛选方法 |
-
2023
- 2023-02-02 CN CN202310052146.XA patent/CN116400082A/zh active Pending
- 2023-06-13 WO PCT/CN2023/099895 patent/WO2023241565A1/zh unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2023241565A1 (zh) | 2023-12-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Piouka et al. | Anti-Mullerian hormone levels reflect severity of PCOS but are negatively influenced by obesity: relationship with increased luteinizing hormone levels | |
| Sims et al. | Abnormalities in proinsulin processing in islets from individuals with longstanding T1D | |
| Zhang et al. | TMT based proteomic analysis of human follicular fluid from overweight/obese and normal-weight patients with polycystic ovary syndrome | |
| Jin et al. | Colonic interleukin‐22 protects intestinal mucosal barrier and microbiota abundance in severe acute pancreatitis | |
| Minatoya et al. | Relation of serum adiponectin levels and obesity with breast cancer: a Japanese case-control study | |
| Mierzyński et al. | The potential role of chemerin, lipocalin 2, and apelin in the diagnosis and pathophysiology of gestational diabetes mellitus | |
| Zhang et al. | Long-term vitamin D deficiency promotes renal fibrosis and functional impairment in middle-aged male mice | |
| Chen et al. | Macroautophagy involved in testosterone synthesis in Leydig cells of male dairy goat (Capra hircus) | |
| Weiwei et al. | Expressions of adiponectin receptors in placenta and their correlation with preeclampsia | |
| Zhou et al. | Altered expressions of AQP3 and ADP are closely related with the risk of preeclampsia occurrence | |
| Ma et al. | Effects of melatonin on development and hormone secretion of sheep theca cells in vitro | |
| CN113577047A (zh) | 调控ApoC3表达量的制剂在制备预防或治疗胰岛素抵抗型多囊卵巢综合征药物中的应用 | |
| Bakhshalizadeh et al. | Assessment of PGC1α-FNDC5 axis in granulosa cells of PCOS mouse model | |
| WO2023241565A1 (zh) | 检测ApoC3蛋白含量的试剂在制备预测卵母细胞发育试剂中的应用 | |
| Zhang et al. | Preliminary study of Yulin mixture affecting the miR-320/SF-1/Cyp19a1 on mouse polycystic ovary syndrome model | |
| Mohammad et al. | Serum Nesfatin-1 in patients with type 2 diabetes mellitus: A cross sectional study | |
| Wang et al. | Hyperandrogen-induced polyol pathway flux increase affects ovarian function in polycystic ovary syndrome via excessive oxidative stress | |
| CN112680512B (zh) | 一种环状RNA生物标志物circ-Glis3的应用 | |
| CN112946299B (zh) | 定量ftl的产品在制备子痫前期诊断工具中的应用 | |
| Ali et al. | Estimation of renin and d-dimer levels in women with polycystic ovary disease with or without coronavirus infection | |
| Rezk et al. | Plasma asprosin levels changes in pregnant and non-pregnant rats with and without gestational diabetes | |
| JP2022539754A (ja) | 子宮内膜受容期を予測する方法 | |
| Matsuzaki et al. | Expression of WT1 is down-regulated in eutopic endometrium obtained during the midsecretory phase from patients with endometriosis | |
| Chen et al. | Study on the correlation of high expression level of HuD with seborrheic keratosis and skin aging | |
| RU2429482C1 (ru) | Способ прогнозирования характера течения аутоиммунной пузырчатки |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |