牛子宫复旧调控机制及促进子宫复旧方法的研究进展

doi:10.11843/j.issn.0366-6964.2023.01.006

摘要/Abstract

摘要： 牛产后子宫复旧延迟会延长繁殖间隔，降低繁殖率。子宫复旧涉及产后子宫组织退化、修复与子宫肌层的重塑，其中干细胞、细胞因子与非编码RNA以及雌激素与孕激素等参与调控产后子宫组织修复与再生。同时，维生素与葡萄糖类物质、中药制剂、免疫调节因子等绿色、无公害防治方法能够有效促进牛产后子宫复旧。本文就牛产后子宫复旧调控机制及促进子宫复旧方法的最新研究进展进行归纳总结，以期为研究动物产后子宫复旧的分子调控机制及研发促进子宫复旧新方法提供一定参考。

关键词: 子宫复旧, 调控机制, 细胞因子, 非编码RNA, 基质金属蛋白酶(MMPs)

Abstract: In cattle, delayed postpartum uterine involution prolongs the reproductive interval and reduces reproductive rates. Uterine involution involves postpartum uterine tissue degeneration, repair, and remodeling of the myometrium. Stem cells, cytokines, non-coding RNAs, estrogen, and progesterone all participate in controlling postpartum uterine tissue repair and regeneration. At the same time, green and non-polluting prevention and treatment techniques such as vitamins and glucose-containing compounds, traditional Chinese medicine preparations, and immunomodulatory chemicals can successfully encourage postpartum uterine involution in cattle. In this article, the latest research progress on the regulatory mechanism of postpartum uterine involution and methods for promoting uterine involution is summarized, in the hope of providing some references for studying the molecular regulatory mechanism of animal postpartum uterine involution and creating new techniques for promoting uterine involution in cattle.

Key words: uterine involution, regulation mechanism, cytokines, non-coding RNA, matrix metalloproteinase system(MMPs)

中图分类号:

S858.237.2

马子明, 郭星汝, 戴天姝, 魏士昊, 史远刚, 淡新刚. 牛子宫复旧调控机制及促进子宫复旧方法的研究进展[J]. 畜牧兽医学报, 2023, 54(1): 58-68.

MA Ziming, GUO Xingru, DAI Tianshu, WEI Shihao, SHI Yuangang, DAN Xingang. Research Progress on Regulatory Mechanism of Cattle Uterine Involution and Methods of Promoting Uterine Involution[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(1): 58-68.

参考文献 84

[1]	SALAMONSEN L A.Tissue injury and repair in the female human reproductive tract[J].Reproduction,2003,125(3):301-311.
[2]	SPOONER M K,LENIS Y Y,WATSON R,et al.The role of stem cells in uterine involution[J].Reproduction,2021,161(3):R61-R77.
[3]	HSU K F,PAN H A,HSU Y Y,et al.Enhanced myometrial autophagy in postpartum uterine involution[J].Taiwan J Obstet Gynecol,2014,53(3):293-302.
[4]	LLEWELLYN S,FITZPATRICK R,KENNY D A,et al.Endometrial expression of the insulin-like growth factor system during uterine involution in the postpartum dairy cow[J].Domest Anim Endocrinol,2008,34(4):391-402.
[5]	NGUYEN T T T N,SHYNLOVA O,LYE S J.Matrix metalloproteinase expression in the rat myometrium during pregnancy,term labor,and postpartum[J].Biol Reprod,2016,95(1):24.
[6]	COUSINS F L,PANDOY R,JIN S Y,et al.The elusive endometrial epithelial stem/progenitor cells[J].Front Cell Dev Biol,2021,9:640319.
[7]	LEE Y J,YI K W.Bone marrow-derived stem cells contribute to regeneration of the endometrium[J].Clin Exp Reprod Med,2018,45(4):149-153.
[8]	SANTAMARIA X,MAS A,CERVELLÓ I,et al.Uterine stem cells:from basic research to advanced cell therapies[J].Hum Reprod Update,2018,24(6):673-693.
[9]	YIN M Z,ZHOU H J,LIN C X,et al.CD34+KLF4+ stromal stem cells contribute to endometrial regeneration and repair[J].Cell Rep,2019,27(9):2709-2724.e3.
[10]	LV Q Y,WANG L L,LUO X Z,et al.Adult stem cells in endometrial regeneration:molecular insights and clinical applications[J].Mol Reprod Dev,2021,88(6):379-394.
[11]	EVANS J,SALAMONSEN L A,WINSHIP A,et al.Fertile ground:human endometrial programming and lessons in health and disease[J].Nat Rev Endocrinol,2016,12(11):654-667.
[12]	GARGETT C E,SCHWAB K E,DEANE J A.Endometrial stem/progenitor cells:the first 10 years[J].Hum Reprod Update,2016,22(2):137-163.
[13]	GUILLAMAT-PRATS R.The role of MSC in wound healing,scarring and regeneration[J].Cells,2021,10(7):1729.
[14]	LEÑERO C,BOWLES A C,CORREA D,et al.Characterization and response to inflammatory stimulation of human endometrial-derived mesenchymal stem/stromal cells[J].Cytotherapy,2022,24(2):124-136.
[15]	NUSSE R,CLEVERS H.Wnt/β-catenin signaling,disease,and emerging therapeutic modalities[J].Cell,2017,169(6):985-999.
[16]	CAO M Z,CHAN R W S,CHENG F H C,et al.Myometrial cells stimulate self-renewal of endometrial mesenchymal stem-like cells through WNT5A/β-catenin signaling[J].Stem Cells,2019,37(11):1455-1466.
[17]	BUKOWSKA J,ZIECIK A J,LAGUNA J,et al.The importance of the canonical wnt signaling pathway in the porcine endometrial stromal stem/progenitor cells:implications for regeneration[J].Stem Cells Dev,2015,24(24):2873-2885.
[18]	MIKELS A J,NUSSE R.Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context[J].PLoS Biol,2006,4(4):e115.
[19]	TATEBAYASHI R,NAKAMURA S,MINABE S,et al.Gene-expression profile and postpartum transition of bovine endometrial side population cells[J].Biol Reprod,2021,104(4):850-860.
[20]	GAO L F,HUANG Z W,LIN H Y J,et al.Bone marrow mesenchymal stem cells (BMSCs) restore functional endometrium in the rat model for severe asherman syndrome[J].Reprod Sci,2019,26(3):436-444.
[21]	GARGETT C E,NGUYEN H P T,YE L.Endometrial regeneration and endometrial stem/progenitor cells[J].Rev Endocr Metab Disord,2012,13(4):235-251.
[22]	LI S Y,DING L J.Endometrial perivascular progenitor cells and uterus regeneration[J].J Pers Med,2021,11(6):477.
[23]	ZHU X X,YU F,YAN G J,et al.Human endometrial perivascular stem cells exhibit a limited potential to regenerate endometrium after xenotransplantation[J].Hum Reprod,2021,36(1):145-159.
[24]	ZHANG L,LI Y,GUAN C Y,et al.Therapeutic effect of human umbilical cord-derived mesenchymal stem cells on injured rat endometrium during its chronic phase[J].Stem Cell Res Ther,2018,9(1):36.
[25]	KRAEMER W J,RATAMESS N A,HYMER W C,et al.Growth hormone(s),testosterone,insulin-like growth factors,and cortisol:roles and integration for cellular development and growth with exercise[J].Front Endocrinol (Lausanne),2020,11:33.
[26]	HAKUNO F,TAKAHASHI S I.40 YEARS OF IGF1:IGF1 receptor signaling pathways[J].J Mol Endocrinol,2018,61(1):T69-T86.
[27]	MIRICESCU D,TOTAN A,STANESCU-SPINU I I,et al.PI3K/AKT/mTOR signaling pathway in breast cancer:from molecular landscape to clinical aspects[J].Int J Mol Sci,2020,22(1):173.
[28]	AǦAOǦLU Ö K,AǦAOǦLU A R,ÖZMEN O,et al.Expression of the insulin-like growth factor (IGF) gene family in feline uterus during pregnancy[J].Biotech Histochem,2021,96(6):439-449.
[29]	WANG Y,HAN X F,TAN Z L,et al.Rumen-protected glucose stimulates the insulin-like growth factor system and mTOR/AKT pathway in the endometrium of early postpartum dairy cows[J].Animals,2020,10(2):357.
[30]	VALDMANN M,KURYKIN J,KAART T,et al.Relationships between plasma insulin-like growth factor-1 and insulin concentrations in multiparous dairy cows with cytological endometritis[J].Vet Rec,2018,183(4):126.
[31]	BACH L A.What happened to the IGF binding proteins?[J].Endocrinology,2018,159(2):570-578.
[32]	GENG J N,HUANG C,JIANG S W.Roles and regulation of the matrix metalloproteinase system in parturition[J].Mol Reprod Dev,2016,83(4):276-286.
[33]	GOBIN E,BAGWELL K,WAGNER J,et al.A pan-cancer perspective of matrix metalloproteases (MMP) gene expression profile and their diagnostic/prognostic potential[J].BMC Cancer,2019,19(1):581.
[34]	HEMERS E,DUVAL C,MCCAIG C,et al.Insulin-like growth factor binding protein-5 is a target of matrix metalloproteinase-7:implications for epithelial-mesenchymal signaling[J].Cancer Res,2005,65(16):7363-7369.
[35]	GUAN S P,LAM A T L,NEWMAN J P,et al.Matrix metalloproteinase-1 facilitates MSC migration via cleavage of IGF-2/IGFBP2 complex[J].FEBS Open Bio,2018,8(1):15-26.
[36]	SAWICKI G,LEON H,SAWICKA J,et al.Degradation of myosin light chain in isolated rat hearts subjected to ischemia-reperfusion injury:a new intracellular target for matrix metalloproteinase-2[J].Circulation,2005,112(4):544-552.
[37]	LOMBARDI A,MAKIEVA S,RINALDI S F,et al.Expression of matrix metalloproteinases in the mouse uterus and human myometrium during pregnancy,labor,and preterm labor[J].Reprod Sci,2018,25(6):938-949.
[38]	YANG H,FU L,LUO Q F,et al.Identification and validation of key miRNAs and miRNA-mRNA regulatory network associated with uterine involution in postpartum Kazakh sheep[J].Arch Anim Breed,2021,64(1):119-129.
[39]	ANTON L,DEVINE A,SIERRA L J,et al.miR-143 and miR-145 disrupt the cervical epithelial barrier through dysregulation of cell adhesion,apoptosis and proliferation[J].Sci Rep,2017,7(1):3020.
[40]	YUAN D Z,LEI Y,ZHAO D,et al.Progesterone-induced miR-145/miR-143 inhibits the proliferation of endometrial epithelial cells[J].Reprod Sci,2019,26(2):233-243.
[41]	AN X P,LIU X R,ZHANG L,et al.MiR-449a regulates caprine endometrial stromal cell apoptosis and endometrial receptivity[J].Sci Rep,2017,7(1):12248.
[42]	CHIUMIA D,SCHULKE K,GROEBNER A E,et al.Initiation of conceptus elongation coincides with an endometrium basic fibroblast growth factor (FGF2) protein increase in heifers[J].Int J Mol Sci,2020,21(5):1584.
[43]	HARDY D B,JANOWSKI B A,COREY D R,et al.Progesterone receptor plays a major antiinflammatory role in human myometrial cells by antagonism of nuclear factor-κB activation of cyclooxygenase 2 expression[J].Mol Endocrinol,2006,20(11):2724-2733.
[44]	MENDELSON C R,GAO L,MONTALBANO A P.Multifactorial regulation of myometrial contractility during pregnancy and parturition[J].Front Endocrinol (Lausanne),2019,10:714.
[45]	KAYISLI O G,KAYISLI U A,LULECI G,et al.In vivo and in vitro regulation of Akt activation in human endometrial cells is estrogen dependent[J].Biol Reprod,2004,71(3):714-721.
[46]	MARUYAMA T,YOSHIMURA Y.Molecular and cellular mechanisms for differentiation and regeneration of the uterine endometrium[J].Endocr J,2008,55(5):795-810.
[47]	MACHADO V S,SILVA T H.Adaptive immunity in the postpartum uterus:potential use of vaccines to control metritis[J].Theriogenology,2020,150:201-209.
[48]	GALVĀO K N,BICALHO R C,JEON S J.Symposium review:the uterine microbiome associated with the development of uterine disease in dairy cows[J].J Dairy Sci,2019,102(12):11786-11797.
[49]	BRODZKI P,BRODZKI A,KUREK Ƚ,et al.Effect of uterine inflammatory status as well as calcium and magnesium concentrations on the uterine involution process in dairy cows[J].Ann Anim Sci,2016,16(3):759-768.
[50]	WANG Y,WANG J F,LI H T,et al.Characterization of the cervical bacterial community in dairy cows with metritis and during different physiological phases[J].Theriogenology,2018,108:306-313.
[51]	BJÖRKMAN S,OLIVIERO C,KAUFFOLD J,et al.Prolonged parturition and impaired placenta expulsion increase the risk of postpartum metritis and delay uterine involution in sows[J].Theriogenology,2018,106:87-92.
[52]	ZINICOLA M,BICALHO M L S,SANTIN T,et al.Effects of recombinant bovine interleukin-8(rbIL-8) treatment on health,metabolism,and lactation performance in Holstein cattle II:postpartum uterine health,ketosis,and milk production[J].J Dairy Sci,2019,102(11):10316-10328.
[53]	ZDUN'CZYK S,JANOWSKI T.Bacteriophages and associated endolysins in therapy and prevention of mastitis and metritis in cows:current knowledge[J].Anim Reprod Sci,2020,218:106504.
[54]	MACHADO V S,BICALHO M L S,PEREIRA R V,et al.The effect of intrauterine administration of mannose or bacteriophage on uterine health and fertility of dairy cows with special focus on Escherichia coli and Arcanobacterium pyogenes[J].J Dairy Sci,2012,95(6):3100-3109.
[55]	MEIRA E B S JR,ROSSI R S,TEIXEIRA A G,et al.The effect of prepartum intravaginal bacteriophage administration on the incidence of retained placenta and metritis[J].J Dairy Sci,2013,96(12):7658-7665.
[56]	DAETZ R,CUNHA F,BITTAR J H,et al.Clinical response after chitosan microparticle administration and preliminary assessment of efficacy in preventing metritis in lactating dairy cows[J].J Dairy Sci,2016,99(11):8946-8955.
[57]	MEIRA E B S JR,ELLINGTON-LAWRENCE R D,SILVA J C C,et al.Recombinant protein subunit vaccine reduces puerperal metritis incidence and modulates the genital tract microbiome[J].J Dairy Sci,2020,103(8):7364-7376.
[58]	MACHADO V S,DE SOUZA BICALHO M L,DE SOUZA MEIRA JUNIOR E B,et al.Subcutaneous immunization with inactivated bacterial components and purified protein of Escherichia coli,Fusobacterium necrophorum and Trueperella pyogenes prevents puerperal metritis in Holstein dairy cows[J].PLoS One,2014,9(3):e91734.
[59]	CUI L Y,QU Y,CAI H L,et al.Meloxicam inhibited the proliferation of LPS-stimulated bovine endometrial epithelial cells through Wnt/β-catenin and PI3K/AKT pathways[J].Front Vet Sci,2021,8:637707.
[60]	LOMB J,NEAVE H W,WEARY D M,et al.Changes in feeding,social,and lying behaviors in dairy cows with metritis following treatment with a nonsteroidal anti-inflammatory drug as adjunctive treatment to an antimicrobial[J].J Dairy Sci,2018,101(5):4400-4411.
[61]	PASCOTTINI O B,VAN SCHYNDEL S J,SPRICIGO J F W,et al.Effect of anti-inflammatory treatment on systemic inflammation,immune function,and endometrial health in postpartum dairy cows[J].Sci Rep,2020,10(1):5236.
[62]	AMIRIDIS G S,LEONTIDES L,TASSOS E,et al.Flunixin meglumine accelerates uterine involution and shortens the calving-to-first-oestrus interval in cows with puerperal metritis[J].J Vet Pharmacol Ther,2001,24(5):365-367.
[63]	RODRÍGUEZ A R,PALMA P I,SOLAR M A,et al.Early postpartum treatment with carprofen in a dairy herd with high incidence of clinical metritis-a case study[J].J Appl Anim Res,2021,49(1):139-146.
[64]	WITTE T S,IWERSEN M,KAUFMANN T,et al.Determination of ceftiofur derivatives in serum,endometrial tissue,and lochia in puerperal dairy cows after subcutaneous administration of ceftiofur crystalline free acid[J].J Dairy Sci,2011,94(1):284-290.
[65]	CREDILLE B C,GIGUōRE S,VICKROY T W,et al.Disposition of ampicillin trihydrate in plasma,uterine tissue,lochial fluid,and milk of postpartum dairy cattle[J].J Vet Pharmacol Ther,2015,38(4):330-335.
[66]	RISCO C A,HERNANDEZ J.Comparison of ceftiofur hydrochloride and estradiol cypionate for metritis prevention and reproductive performance in dairy cows affected with retained fetal membranes[J].Theriogenology,2003,60(1):47-58.
[67]	KAEWLAMUN W,OKOUYI M,HUMBLOT P,et al.Does supplementing dairy cows with β-carotene during the dry period affect postpartum ovarian activity,progesterone,and cervical and uterine involution?[J].Theriogenology,2011,75(6):1029-1038.
[68]	GULLIVER C E,FRIEND M A,KING B J,et al.The role of omega-3 polyunsaturated fatty acids in reproduction of sheep and cattle[J].Anim Reprod Sci,2012,131(1-2):9-22.
[69]	DE MEDEIROS FERREIRA J R,VILLELA S B,BIANCONI C,et al.Uterine involution of mares supplemented with dietary algae-derived omega-3 fatty acids during the peripartum period[J].J Equine Vet Sci,2021,106:103733.
[70]	ULFINA G G,KIMOTHI S P,OBEROI P S,et al.Modulation of post-partum reproductive performance in dairy cows through supplementation of long-or short-chain fatty acids during transition period[J].J Anim Physiol Anim Nutr,2015,99(6):1056-1064.
[71]	FORBES B E,BLYTH A J,WIT J M.Disorders of IGFs and IGF-1R signaling pathways[J].Mol Cell Endocrinol,2020,518:111035.
[72]	VENKATA K C N,SWAROOP A,BAGCHI D,et al.A small plant with big benefits:fenugreek (Trigonella foenum-graecum Linn.) for disease prevention and health promotion[J].Mol Nutr Food Res,2017,61(6):1600950.
[73]	BERNHARDT V,D'SOUZA J R T.Immunomodulatory potential of herbal medicine in type 2 DM patients as evaluvated by neutrophil phagocytic index,serum opsonisation and lymphocyte proliferation rate[J].Asian J Pharm Clin Res,2012,5(2):36-41.
[74]	黄梅,沈建英,杜成成,等.青蒿素及其衍生物的抗菌活性初步研究[J].中国中药杂志,2019,44(9):1946-1952.HUANG M,SHEN J Y,DU C C,et al.Preliminary study on antibacterial activity of artemisinin and its derivatives[J].China Journal of Chinese Materia Medica,2019,44(9):1946-1952.(in Chinese)
[75]	BAHUGUNA A,RAMALINGAM S,ARUMUGAM A,et al.Molecular and in silico evidences explain the anti-inflammatory effect of Trachyspermum ammi essential oil in lipopolysaccharide induced macrophages[J].Process Biochem,2020,96:138-145.
[76]	JAPHETH K P,KUMARESAN A,PATBANDHA T K,et al.Supplementation of a combination of herbs improves immunity,uterine cleansing and facilitate early resumption of ovarian cyclicity:a study on post-partum dairy buffaloes[J].J Ethnopharmacol,2021,272:113931.
[77]	LEE K H,LEE Y T,CHEN T C,et al.Effects of Sheng Hua Tang on uterine involution and ovarian activity in postpartum dairy cows[J].Asian-Australas J Anim Sci,2013,26(9):1247-1254.
[78]	STEPHEN C P,JOHNSON W H,LEBLANC S J,et al.The impact of ecbolic therapy in the early postpartum period on uterine involution and reproductive health in dairy cows[J].J Vet Med Sci,2019,81(3):491-498.
[79]	YU G M,BAI J H,LIU Y,et al.A weekly postpartum PGF2αprotocol enhances uterine health in dairy cows[J].Reprod Biol,2016,16(4):295-299.
[80]	MELENDEZ P,MCHALE J,BARTOLOME J,et al.Uterine involution and fertility of holstein cows subsequent to early postpartum PGF2α treatment for acute puerperal metritis[J].J Dairy Sci,2004,87(10):3238-3246.
[81]	CANADAS E R,LONERGAN P,BUTLER S T.Effect of equine chorionic gonadotropin administration on day 8 post-partum on ovarian follicular development,uterine health and uterine involution in lactating dairy cows[J].Theriogenology,2019,123:54-61.
[82]	WANG X R,BAO H C,LIU X M,et al.Effects of endometrial stem cell transplantation combined with estrogen in the repair of endometrial injury[J].Oncol Lett,2018,16(1):1115-1122.
[83]	LIU X R,ZHANG L,LIU Y X,et al.Circ-8073 regulates CEP55 by sponging miR-449a to promote caprine endometrial epithelial cells proliferation via the PI3K/AKT/mTOR pathway[J].Biochim Biophys Acta Mol Cell Res,2018,1865(8):1130-1147.
[84]	DENG Q,ODHIAMBO J F,FAROOQ U,et al.Intravaginally administered lactic acid bacteria expedited uterine involution and modulated hormonal profiles of transition dairy cows[J].J Dairy Sci,2015,98(9):6018-6028.