دورية أكاديمية
Luteinizing Hormone Receptor Mutation (LHR N316S ) Causes Abnormal Follicular Development Revealed by Follicle Single-Cell Analysis and CRISPR/Cas9.
| العنوان: | Luteinizing Hormone Receptor Mutation (LHR N316S ) Causes Abnormal Follicular Development Revealed by Follicle Single-Cell Analysis and CRISPR/Cas9. |
|---|---|
| المؤلفون: | Zhang C; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200240, China.; Department of Hematology, Tangdu Hospital, Xi'an, 710032, China., Nie Y; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200240, China., Xu B; Department of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China., Mu C; School of Basic Medical Sciences, Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, 750004, China., Tian GG; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200240, China., Li X; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200240, China., Cheng W; International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China. 18017316001@163.com., Zhang A; Department of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. zhaj1268@163.com., Li D; Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China. dlli@bio.ecnu.edu.cn., Wu J; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200240, China. jiwu@sjtu.edu.cn.; School of Basic Medical Sciences, Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, 750004, China. jiwu@sjtu.edu.cn. |
| المصدر: | Interdisciplinary sciences, computational life sciences [Interdiscip Sci] 2024 Aug 16. Date of Electronic Publication: 2024 Aug 16. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 101515919 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1867-1462 (Electronic) Linking ISSN: 18671462 NLM ISO Abbreviation: Interdiscip Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Heidelberg] : Springer-Verlag |
| مستخلص: | Abnormal interaction between granulosa cells and oocytes causes disordered development of ovarian follicles. However, the interactions between oocytes and cumulus granulosa cells (CGs), oocytes and mural granulosa cells (MGs), and CGs and MGs remain to be fully explored. Using single-cell RNA-sequencing (scRNA-seq), we determined the transcriptional profiles of oocytes, CGs and MGs in antral follicles. Analysis of scRNA-seq data revealed that CGs may regulate follicular development through the BMP15-KITL-KIT-PI3K-ARF6 pathway with elevated expression of luteinizing hormone receptor (LHR). Because internalization of the LHR is regulated by Arf6, we constructed LHR N316S mice by CRISPR/Cas9 to further explore mechanisms of follicular development and novel treatment strategies for female infertility. Ovaries of LHR N316S mice exhibited reduced numbers of corpora lutea and ovulation. The LHR N316S mice had a reduced rate of oocyte maturation in vitro and decreased serum progesterone levels. Mating LHR N316S female mice with ICR wild type male mice revealed that the infertility rate of LHR N316S mice was 21.4% (3/14). Litter sizes from LHR N316S mice were smaller than those from control wild type female mice. The oocytes from LHR N316S mice had an increased rate of maturation in vitro after progesterone administration in vitro. Furthermore, progesterone treated LHR N316S mice produced offspring numbers per litter equivalent to WT mice. These findings provide key insights into cellular interactions in ovarian follicles and provide important clues for infertility treatment. (© 2024. The Author(s).) |
| References: | Kidder GM, Vanderhyden BC (2010) Bidirectional communication between oocytes and follicle cells: ensuring oocyte developmental competence. Can J Physiol Pharmacol 88:399–413. https://doi.org/10.1139/y10-009. (PMID: 10.1139/y10-009205554083025001) Dupont J, Scaramuzzi RJ (2016) Insulin signalling and glucose transport in the ovary and ovarian function during the ovarian cycle. Biochem J 473:1483–1501. https://doi.org/10.1042/BCJ20160124. (PMID: 10.1042/BCJ2016012427234585) Brunet S, Maro B (2007) Germinal vesicle position and meiotic maturation in mouse oocyte. Reproduction 133:1069–1072. https://doi.org/10.1530/REP-07-0036. (PMID: 10.1530/REP-07-003617636161) Barrett SL, Albertini DF (2010) Cumulus cell contact during oocyte maturation in mice regulates meiotic spindle positioning and enhances developmental competence. J Assist Reprod Genet 27:29–39. https://doi.org/10.1007/s10815-009-9376-9. (PMID: 10.1007/s10815-009-9376-920039198) Gittens JE, Barr KJ, Vanderhyden BC et al (2005) Interplay between paracrine signaling and gap junctional communication in ovarian follicles. J Cell Sci 118:113–122. https://doi.org/10.1242/jcs.01587. (PMID: 10.1242/jcs.0158715585573) Pelland AM, Corbett HE, Baltz JM (2009) Amino acid transport mechanisms in mouse oocytes during growth and meiotic maturation. Biol Reprod 81:1041–1054. https://doi.org/10.1095/biolreprod.109.079046. (PMID: 10.1095/biolreprod.109.079046196057822844491) Su YQ, Sugiura K, Wigglesworth K et al (2008) Oocyte regulation of metabolic cooperativity between mouse cumulus cells and oocytes: BMP15 and GDF9 control cholesterol biosynthesis in cumulus cells. Development 135:111–121. https://doi.org/10.1242/dev.009068. (PMID: 10.1242/dev.00906818045843) Fan HY, Liu Z, Cahill N et al (2008) Targeted disruption of Pten in ovarian granulosa cells enhances ovulation and extends the life span of luteal cells. Mol Endocrinol 22:2128–2140. https://doi.org/10.1210/me.2008-0095. (PMID: 10.1210/me.2008-0095186068602631369) Kawamura K, Cheng Y, Suzuki N et al (2013) Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proc Natl Acad Sci USA 110:17474–17479. https://doi.org/10.1073/pnas.1312830110. (PMID: 10.1073/pnas.1312830110240820833808580) Nagashima T, Kim J, Li Q et al (2011) Connective tissue growth factor is required for normal follicle development and ovulation. Mol Endocrinol 25:1740–1759. https://doi.org/10.1210/me.2011-1045. (PMID: 10.1210/me.2011-1045218684533182424) Wigglesworth K, Lee KB, Emori C et al (2015) Transcriptomic diversification of developing cumulus and mural granulosa cells in mouse ovarian follicles. Biol Reprod 92:23. https://doi.org/10.1095/biolreprod.114.121756. (PMID: 10.1095/biolreprod.114.12175625376232) Chen J, Torcia S, Xie F et al (2013) Somatic cells regulate maternal mRNA translation and developmental competence of mouse oocytes. Nat Cell Biol 15:1415–1423. https://doi.org/10.1038/ncb2873. (PMID: 10.1038/ncb2873242708884066669) Hummitzsch K, Anderson RA, Wilhelm D et al (2015) Stem cells, progenitor cells, and lineage decisions in the ovary. Endocr Rev 36:65–91. https://doi.org/10.1210/er.2014-1079. (PMID: 10.1210/er.2014-107925541635) Diaz FJ, Wigglesworth K, Eppig JJ (2007) Oocytes determine cumulus cell lineage in mouse ovarian follicles. J Cell Sci 120:1330–1340. https://doi.org/10.1242/jcs.000968. (PMID: 10.1242/jcs.00096817389684) Eppig JJ (2001) Oocyte control of ovarian follicular development and function in mammals. Reproduction 122:829–838. https://doi.org/10.1530/rep.0.1220829. (PMID: 10.1530/rep.0.122082911732978) Hussein TS, Thompson JG, Gilchrist RB (2006) Oocyte-secreted factors enhance oocyte developmental competence. Dev Biol 296:514–521. https://doi.org/10.1016/j.ydbio.2006.06.026. (PMID: 10.1016/j.ydbio.2006.06.02616854407) Su YQ, Wu X, O’Brien MJ et al (2004) Synergistic roles of BMP15 and GDF9 in the development and function of the oocyte-cumulus cell complex in mice: genetic evidence for an oocyte-granulosa cell regulatory loop. Dev Biol 276:64–73. https://doi.org/10.1016/j.ydbio.2004.08.020. (PMID: 10.1016/j.ydbio.2004.08.02015531364) Zhang Y, Yan Z, Qin Q et al (2018) Transcriptome landscape of human folliculogenesis reveals oocyte and granulosa cell interactions. Mol Cell 72(1021–1034):e4. https://doi.org/10.1016/j.molcel.2018.10.029. (PMID: 10.1016/j.molcel.2018.10.029) Donaldson JG, Jackson CL (2011) ARF family G proteins and their regulators: roles in membrane transport, development and disease. Nat Rev Mol Cell Biol 12:362–375. https://doi.org/10.1038/nrm3117. (PMID: 10.1038/nrm3117215872973245550) Cavenagh MM, Whitney JA, Carroll K et al (1996) Intracellular distribution of Arf proteins in mammalian cells. Arf6 is uniquely localized to the plasma membrane. J Biol Chem 271:21767–21774. https://doi.org/10.1074/jbc.271.36.21767. (PMID: 10.1074/jbc.271.36.217678702973) Duan X, Zhang HL, Pan MH et al (2018) Vesicular transport protein Arf6 modulates cytoskeleton dynamics for polar body extrusion in mouse oocyte meiosis. Biochim Biophys Acta Mol Cell Res 1865:455–462. https://doi.org/10.1016/j.bbamcr.2017.11.016. (PMID: 10.1016/j.bbamcr.2017.11.01629208529) Claing A (2004) Regulation of G protein-coupled receptor endocytosis by ARF6 GTP-binding proteins. Biochem Cell Biol 82:610–617. https://doi.org/10.1139/o04-113. (PMID: 10.1139/o04-11315674428) Suzuki T, Kanai Y, Hara T et al (2006) Crucial role of the small GTPase ARF6 in hepatic cord formation during liver development. Mol Cell Biol 26:6149–6156. https://doi.org/10.1128/MCB.00298-06. (PMID: 10.1128/MCB.00298-06168805251592812) Breen SM, Andric N, Ping T et al (2013) Ovulation involves the luteinizing hormone-dependent activation of G(q/11) in granulosa cells. Mol Endocrinol 27:1483–1491. https://doi.org/10.1210/me.2013-1130. (PMID: 10.1210/me.2013-1130238369243753423) Ascoli M, Fanelli F, Segaloff DL (2002) The lutropin/choriogonadotropin receptor, a 2002 perspective. Endocr Rev 23:141–174. https://doi.org/10.1210/edrv.23.2.0462. (PMID: 10.1210/edrv.23.2.046211943741) Themmen AP (2005) An update of the pathophysiology of human gonadotrophin subunit and receptor gene mutations and polymorphisms. Reproduction 130:263–274. https://doi.org/10.1530/rep.1.00663. (PMID: 10.1530/rep.1.0066316123233) Lindgren I, Nenonen H, Henic E et al (2019) Gonadotropin receptor variants are linked to cumulative live birth rate after in vitro fertilization. J Assist Reprod Genet 36:29–38. https://doi.org/10.1007/s10815-018-1318-y. (PMID: 10.1007/s10815-018-1318-y30232643) Nagulapalli A, Vembu R, Pandurangi M et al (2023) Luteinizing hormone/human chorionic gonadotropin receptor N312S single-nucleotide polymorphism and its impact on clinical and reproductive outcomes in assisted reproductive technology: a prospective cohort study. Cureus 15:e47217. https://doi.org/10.7759/cureus.47217. (PMID: 10.7759/cureus.472173802216710652146) Pirtea P, de Ziegler D, Marin D et al (2022) Gonadotropin receptor polymorphisms (FSHR N680S and LHCGR N312S) are not predictive of clinical outcome and live birth in assisted reproductive technology. Fertil Steril 118:494–503. https://doi.org/10.1016/j.fertnstert.2022.06.011. (PMID: 10.1016/j.fertnstert.2022.06.01135842313) Jin H, Yang H, Zheng J et al (2023) Post-trigger luteinizing hormone concentration to positively predict oocyte yield in the antagonist protocol and its association with genetic variants of LHCGR. J Ovarian Res 16:189. https://doi.org/10.1186/s13048-023-01271-6. (PMID: 10.1186/s13048-023-01271-63769110210494325) Xue ZG, Huang K, Cai CC et al (2013) Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing. Nature 500:593–597. https://doi.org/10.1038/nature12364. (PMID: 10.1038/nature12364238927784950944) Pujana MA, Han JDJ, Starita LM et al (2007) Network modeling links breast cancer susceptibility and centrosome dysfunction. Nat Genet 39:1338–1349. https://doi.org/10.1038/ng.2007.2. (PMID: 10.1038/ng.2007.217922014) Prieto C, Risueno A, Fontanillo C et al (2008) Human gene coexpression landscape: confident network derived from tissue transcriptomic profiles. PLoS ONE 3:e3911. https://doi.org/10.1371/journal.pone.0003911. (PMID: 10.1371/journal.pone.0003911190817922597745) Barabasi AL, Oltvai ZN (2004) Network biology: understanding the cell’s functional organization. Nat Rev Genet 5:101–113. https://doi.org/10.1038/nrg1272. (PMID: 10.1038/nrg127214735121) Ashburner M, Ball CA, Blake JA et al (2000) Gene ontology: tool for the unification of biology. Nat Genet 25:25–29. https://doi.org/10.1038/75556. (PMID: 10.1038/75556108026513037419) Dupont J, Reverchon M, Cloix L et al (2012) Involvement of adipokines, AMPK, PI3K and the PPAR signaling pathways in ovarian follicle development and cancer. Int J Dev Biol 56:959–967. https://doi.org/10.1387/ijdb.120134jd. (PMID: 10.1387/ijdb.120134jd23417417) Shao YJ, Guan YT, Wang LR et al (2014) CRISPR/Cas-mediated genome editing in the rat via direct injection of one-cell embryos. Nat Protoc 9:2493–2512. https://doi.org/10.1038/nprot.2014.171. (PMID: 10.1038/nprot.2014.17125255092) Packer AI, Hsu YC, Besmer P et al (1994) The ligand of the c-kit receptor promotes oocyte growth. Dev Biol 161:194–205. https://doi.org/10.1006/dbio.1994.1020. (PMID: 10.1006/dbio.1994.10207507447) Ye Y, Kawamura K, Sasaki M et al (2009) Kit ligand promotes first polar body extrusion of mouse preovulatory oocytes. Reprod Biol Endocrinol 7:26. https://doi.org/10.1186/1477-7827-7-26. (PMID: 10.1186/1477-7827-7-26193414832676294) Hsueh AJ (2014) Fertility: the role of mTOR signaling and KIT ligand. Curr Biol 24:R1040–R1042. https://doi.org/10.1016/j.cub.2014.09.033. (PMID: 10.1016/j.cub.2014.09.03325517366) Jagarlamudi K, Rajkovic A (2012) Oogenesis: transcriptional regulators and mouse models. Mol Cell Endocrinol 356:31–39. https://doi.org/10.1016/j.mce.2011.07.049. (PMID: 10.1016/j.mce.2011.07.04921856374) Jones RL, Pepling ME (2013) KIT signaling regulates primordial follicle formation in the neonatal mouse ovary. Dev Biol 382:186–197. https://doi.org/10.1016/j.ydbio.2013.06.030. (PMID: 10.1016/j.ydbio.2013.06.03023831378) Morohaku K, Tanimoto R, Sasaki K et al (2016) Complete in vitro generation of fertile oocytes from mouse primordial germ cells. Proc Natl Acad Sci USA 113:9021–9026. https://doi.org/10.1073/pnas.1603817113. (PMID: 10.1073/pnas.1603817113274579284987791) Davies JC, Tamaddon-Jahromi S, Jannoo R et al (2014) Cytohesin 2/ARF6 regulates preadipocyte migration through the activation of ERK1/2. Biochem Pharmacol 92:651–660. https://doi.org/10.1016/j.bcp.2014.09.023. (PMID: 10.1016/j.bcp.2014.09.02325450674) Lees-Murdock DJ, Lau HT, Castrillon DH et al (2008) DNA methyltransferase loading, but not de novo methylation, is an oocyte-autonomous process stimulated by SCF signalling. Dev Biol 321:238–250. https://doi.org/10.1016/j.ydbio.2008.06.024. (PMID: 10.1016/j.ydbio.2008.06.02418616936) Salvador LM, Mukherjee S, Kahn RA et al (2001) Activation of the luteinizing hormone/choriogonadotropin hormone receptor promotes ADP ribosylation factor 6 activation in porcine ovarian follicular membranes. J Biol Chem 276:33773–33781. https://doi.org/10.1074/jbc.M101498200. (PMID: 10.1074/jbc.M10149820011448949) Mukherjee S, Gurevich VV, Jones JC et al (2000) The ADP ribosylation factor nucleotide exchange factor ARNO promotes beta-arrestin release necessary for luteinizing hormone/choriogonadotropin receptor desensitization. Proc Natl Acad Sci USA 97:5901–5906. https://doi.org/10.1073/pnas.100127097. (PMID: 10.1073/pnas.1001270971081190218531) Lindgren I, Baath M, Uvebrant K et al (2016) Combined assessment of polymorphisms in the LHCGR and FSHR genes predict chance of pregnancy after in vitro fertilization. Hum Reprod 31:672–683. https://doi.org/10.1093/humrep/dev342. (PMID: 10.1093/humrep/dev34226769719) Comazzetto S, Murphy MM, Berto S et al (2019) Restricted hematopoietic progenitors and erythropoiesis require SCF from leptin receptor+ niche cells in the bone marrow. Cell Stem Cell 24(477–486):e6. https://doi.org/10.1016/j.stem.2018.11.022. (PMID: 10.1016/j.stem.2018.11.022) Lennartsson J, Ronnstrand L (2012) Stem cell factor receptor/c-Kit: from basic science to clinical implications. Physiol Rev 92:1619–1649. https://doi.org/10.1152/physrev.00046.2011. (PMID: 10.1152/physrev.00046.201123073628) Liu JC, Yan ZH, Li B et al (2021) Di (2-ethylhexyl) phthalate impairs primordial follicle assembly by increasing PDE3A expression in oocytes. Environ Pollut 270:116088. https://doi.org/10.1016/j.envpol.2020.116088. (PMID: 10.1016/j.envpol.2020.11608833234378) Thomas FH, Vanderhyden BC (2006) Oocyte-granulosa cell interactions during mouse follicular development: regulation of kit ligand expression and its role in oocyte growth. Reprod Biol Endocrinol 4:19. https://doi.org/10.1186/1477-7827-4-19. (PMID: 10.1186/1477-7827-4-19166113641481519) Otsuka F, Shimasaki S (2002) A negative feedback system between oocyte bone morphogenetic protein 15 and granulosa cell kit ligand: its role in regulating granulosa cell mitosis. Proc Natl Acad Sci USA 99:8060–8065. https://doi.org/10.1073/pnas.122066899. (PMID: 10.1073/pnas.12206689912048244123020) Otsuka F, Yao Z, Lee T et al (2000) Bone morphogenetic protein-15. Identification of target cells and biological functions. J Biol Chem 275:39523–39528. https://doi.org/10.1074/jbc.M007428200. (PMID: 10.1074/jbc.M00742820010998422) Celik S, Ozkavukcu S, Celik-Ozenci C (2020) Altered expression of activator proteins that control follicle reserve after ovarian tissue cryopreservation/transplantation and primordial follicle loss prevention by rapamycin. J Assist Reprod Genet 37:2119–2136. https://doi.org/10.1007/s10815-020-01875-7. (PMID: 10.1007/s10815-020-01875-7326516777492284) Sun SC, Sun QY, Kim NH (2011) JMY is required for asymmetric division and cytokinesis in mouse oocytes. Mol Hum Reprod 17:296–304. https://doi.org/10.1093/molehr/gar006. (PMID: 10.1093/molehr/gar00621266449) Li H, Guo F, Rubinstein B et al (2008) Actin-driven chromosomal motility leads to symmetry breaking in mammalian meiotic oocytes. Nat Cell Biol 10:1301–1308. https://doi.org/10.1038/ncb1788. (PMID: 10.1038/ncb178818836438) Kanamarlapudi V, Thompson A, Kelly E et al (2012) ARF6 activated by the LHCG receptor through the cytohesin family of guanine nucleotide exchange factors mediates the receptor internalization and signaling. J Biol Chem 287:20443–20455. https://doi.org/10.1074/jbc.M112.362087. (PMID: 10.1074/jbc.M112.362087225230743370224) Rivron NC, Frias-Aldeguer J, Vrij EJ et al (2018) Blastocyst-like structures generated solely from stem cells. Nature 557:106–111. https://doi.org/10.1038/s41586-018-0051-0. (PMID: 10.1038/s41586-018-0051-029720634) Chian RC, Ao A, Clarke HJ et al (1999) Production of steroids from human cumulus cells treated with different concentrations of gonadotropins during culture in vitro. Fertil Steril 71:61–66. https://doi.org/10.1016/s0015-0282(98)00416-6. (PMID: 10.1016/s0015-0282(98)00416-69935117) Shimada M, Terada T (2002) FSH and LH induce progesterone production and progesterone receptor synthesis in cumulus cells: a requirement for meiotic resumption in porcine oocytes. Mol Hum Reprod 8:612–618. https://doi.org/10.1093/molehr/8.7.612. (PMID: 10.1093/molehr/8.7.61212087075) Cavalieri J (2019) Absence of a corpus luteum and relatively lesser concentrations of progesterone during the period of pre-ovulatory follicle emergence results in lesser pregnancy rates in Bos indicus cattle. Anim Reprod Sci 204:39–49. https://doi.org/10.1016/j.anireprosci.2019.03.003. (PMID: 10.1016/j.anireprosci.2019.03.00330853120) Gaur M, Purohit GN (2019) Follicular dynamics and colour Doppler vascularity evaluations of follicles and corpus luteum in relation to plasma progesterone during the oestrous cycle of Surti buffaloes. Reprod Domest Anim 54:585–594. https://doi.org/10.1111/rda.13400. (PMID: 10.1111/rda.1340030614085) Simon C, Branet L, Moreau J et al (2019) Association between progesterone to number of mature oocytes index and live birth in GnRH antagonist protocols. Reprod Biomed Online 38:901–907. https://doi.org/10.1016/j.rbmo.2019.01.009. (PMID: 10.1016/j.rbmo.2019.01.00930952493) Long H, Yu W, Yu S et al (2021) Progesterone affects clinic oocyte yields by coordinating with follicle stimulating hormone via PI3K/AKT and MAPK pathways. J Adv Res 33:189–199. https://doi.org/10.1016/j.jare.2021.02.008. (PMID: 10.1016/j.jare.2021.02.008346037898463924) Bonato DV, Ferreira EB, Gomes DN et al (2022) Follicular dynamics, luteal characteristics, and progesterone concentrations in synchronized lactating Holstein cows with high and low antral follicle counts. Theriogenology 179:223–229. https://doi.org/10.1016/j.theriogenology.2021.12.006. (PMID: 10.1016/j.theriogenology.2021.12.00634896744) Kornmatitsuk B, Kornmatitsuk S (2021) Circulating progesterone concentrations and preovulatory follicle diameters affecting ovulatory response in crossbred dairy heifers, following a 7-day progesterone-based synchronization protocol. Trop Anim Health Prod 53:102. https://doi.org/10.1007/s11250-020-02494-1. (PMID: 10.1007/s11250-020-02494-133417076) Paulino L, Barroso PAA, Silva AWB et al (2020) Effects of epidermal growth factor and progesterone on development, ultrastructure and gene expression of bovine secondary follicles cultured in vitro. Theriogenology 142:284–290. https://doi.org/10.1016/j.theriogenology.2019.10.031. (PMID: 10.1016/j.theriogenology.2019.10.03131711701) |
| معلومات مُعتمدة: | 2022BFH02004 Key Research and Development Program of Ningxia Hui Autonomous Region; ZH2018ZDA31 the interdisciplinary program of Shanghai Jiao Tong University |
| فهرسة مساهمة: | Keywords: Follicle; Granulosa cells; LHRN316S; Oocytes; Progesterone; Single cell RNA-seq |
| تواريخ الأحداث: | Date Created: 20240816 Latest Revision: 20240816 |
| رمز التحديث: | 20240816 |
| DOI: | 10.1007/s12539-024-00646-7 |
| PMID: | 39150470 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1867-1462 |
|---|---|
| DOI: | 10.1007/s12539-024-00646-7 |