Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Ovarian Research
Published in: Journal of Ovarian Research 1/2018

Open Access 01-12-2018 | Review

Circular RNAs: biogenesis, expression and their potential roles in reproduction

Authors: Guobo Quan, Julang Li

Published in: Journal of Ovarian Research | Issue 1/2018

Login to get access

Abstract

Unlike other non-coding RNAs (ncRNAs), circular RNA (circRNA) is generally presented as a covalently linked circle lacking both a 5′ cap and a 3′ tail. circRNAs were thought to be spliced intermediates, byproducts, or products of abnormal RNA splicing events. However, the high-throughput sequencing technology coupled with bioinformatics has recently uncovered thousands of endogenous circRNAs in cells of many different species. These circRNAs show various features, such as abundant expression, evolutionary conservation, cell- or tissue-specific expression, and a higher resistance to degradation caused by exonuclease or ribonuclease (RNase), suggesting their potentially biological significance. However, the function of these circRNAs, their mechanism of action, and the regulation of their biogenesis and degradation remains largely unclear. The current research and findings of circRNA in the context of reproduction will be reviewed. Additionally, the perspectives of circRNAs in the field will be discussed.
Literature
1.
Wang KS, Choo QL, Weiner AJ, Ou JH, Najarian C, Thayer RM, Mullenbach GT, Denniston KJ, Gerin JL, Houghton M. Structure, sequence and expression of the hepatitis delta viral genome. Nature. 1986;323:508–13.CrossRefPubMed
2.
Rizzetto M, Canese MG, Arico S, Crivelli O, Trepo C, Bonino F, Verme G. Immunofluorescence detection of new antigen-antibody system (delta/anti-delta) associated to hepatitis B virus in liver and in serum of HBsAg carriers. Gut. 1977;18:997–1003.CrossRefPubMedPubMedCentral
3.
Roossinck MJ, Sleat D, Palukaitis P. Satellite RNAs of plant viruses: structures and biological effects. Microbiol Rev. 1992;56:265–79.PubMedPubMedCentral
4.
Sanger HL, Klotz G, Riesner D, Gross HJ, Kleinschmidt AK. Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci U S A. 1976;73:3852–6.CrossRefPubMedPubMedCentral
5.
Coca-Prados M, Hsu MT. Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells. Nature. 1979;280:339–40.CrossRefPubMed
6.
Nigro JM, Cho KR, Fearon ER, Kern SE, Ruppert JM, Oliner JD, Kinzler KW, Vogelstein B. Scrambled exons. Cell. 1991;64:607–13.CrossRefPubMed
7.
Salzman J, Gawad C, Wang PL, Lacayo N, Brown PO. Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS One. 2012;7:e30733.CrossRefPubMedPubMedCentral
8.
9.
10.
11.
Starke S, Jost I, Rossbach O, Schneider T, Schreiner S, Hung LH, Bindereif A. Exon circularization requires canonical splice signals. Cell Rep. 2015;10:103–11.CrossRefPubMed
12.
13.
Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, Marzluff WF, Sharpless NE. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 2013;19:141–57.CrossRefPubMedPubMedCentral
14.
Li Z, Huang C, Bao C, Chen L, Lin M, Wang X, Zhong G, Yu B, Hu W, Dai L, Zhu P, Chang Z, Wu Q, Zhao Y, Jia Y, Xu P, Liu H, Shan G. Exon–intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol. 2015;22:256–64.CrossRefPubMed
15.
Zhang Y, Zhang XO, Chen T, Xiang JF, Yin QF, Xing YH, Zhu S, Yang L, Chen LL. Circular intronic long noncoding RNAs. Mol Cell. 2013;51:792–806.CrossRefPubMed
16.
17.
18.
Chen L, Shan G. Circular RNAs remain peculiarly unclear in biogenesis and function. Sci China Life Sci. 2015;58:616–8.CrossRefPubMed
19.
Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, Loewer A, Ziebold U, Landthaler M, Kocks C, le Noble F, Rajewsky N. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013;495:333–8.CrossRefPubMed
20.
Dong WW, Li HM, Qing XR, Huang DH, Li HG. Identification and characterization of human testis derived circular RNAs and their existence in seminal plasma. Sci Rep. 2016;6(39080)
21.
Qian Y, Lu Y, Rui C, Qian Y, Cai M, Jia R. Potential significance of circular RNA in human placental tissue for patients with preeclampsia. Cell Physiol Biochem. 2016;39:1380–90.CrossRefPubMed
22.
Stiefel F, Fischer S, Hackl M, Handrick R, Hesse F, Borth N, Otte K, Grillari J. Noncoding RNAs, post-transcriptional RNA operons and Chinese hamster ovary cells. Pharm Bioprocess. 2015;3:227–47.CrossRef
23.
Dang Y, Yan L, Hu B, Fan X, Ren Y, Li R, Lian Y, Yan J, Li Q, Zhang Y, Li M, Ren X, Huang J, Wu Y, Liu P, Wen L, Zhang C, Huang Y, Tang F, Qiao J. Tracing the expression of circular RNAs in human pre-implantation embryos. Genome Biol. 2016;17(130)
24.
Ashwal-Fluss R, Meyer M, Pamudurti NR, Ivanov A, Bartok O, Hanan M, Evantal N, Memczak S, Rajewsky N, Kadener S. circRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 2014;56:55–66.CrossRefPubMed
25.
26.
Conn SJ, Pillman KA, Toubia J, Conn VM, Salmanidis M, Phillips CA, Roslan S, Schreiber AW, Gregory PA, Goodall GJ. The RNA binding protein quaking regulates formation of circRNAs. Cell. 2015;160:1125–34.CrossRefPubMed
27.
Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495:384–8.CrossRefPubMed
28.
29.
Ebbesen KK, Hansen TB, Kjems J. Insights into circular RNA biology. RNA Biol. 2017:1–11.
30.
De La Mata M, Alonso CR, Kadener S, Fededa JP, Blaustein M, Pelisch F, Cramer P, Bentley D, Kornblihtt AR. A slow RNA polymerase II affects alternative splicing in vivo. Mol Cell. 2003;(2):525–32.
31.
Ip JY, Schmidt D, Pan Q, Ramani AK, Fraser AG, Odom DT, Blencowe BJ. Global impact of RNA polymerase II elongation inhibition on alternative splicing regulation. Genome Res. 2011;21:390–401.CrossRefPubMedPubMedCentral
32.
Khodor YL, Rodriguez J, Abruzzi KC, Tang CHA, Marr MT, Rosbash M. Nascent-seq indicates widespread cotranscriptional pre-mRNA splicing in drosophila. Genes Dev. 2011;(23):2502–12.
33.
Ivanov A, Memczak S, Wyler E, Torti F, Porath HT, Orejuela MR, Piechotta M, Levanon EY, Landthaler M, Dieterich C, Rajewsky N. Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep. 2015;10:170–7.CrossRefPubMed
34.
Zhang XO, Wang HB, Zhang Y, Lu X, Chen LL, Yang L. Complementary sequence-mediated exon circularization. Cell. 2014;(1):134–47.
35.
36.
Kulcheski FR, Christoff AP, Margis R. Circular RNAs are miRNA sponges and can be used as a new class of biomarker. J Biotechnol. 2016;238:42–51.CrossRefPubMed
37.
Cocquerelle C, Mascrez B, Hetuin D, Bailleul B. Mis-splicing yields circular RNA molecules. FASEB J. 1993;7:155–60.PubMed
38.
Kelly S, Greenman C, Cook PR, Papantonis A. Exon skipping is correlated with exon circularization. J Mol Biol. 2015;427:2414–7.CrossRefPubMed
39.
40.
Suzuki H, Zuo Y, Wang J, Zhang MQ, Malhotra A, Mayeda A. Characterization of RNase R-digested cellular RNA source that consists of lariat and circular RNAs from pre-mRNA splicing. Nucleic Acids Res. 2006;34:e63.CrossRefPubMedPubMedCentral
41.
Zaphiropoulos PG. Circular RNAs from transcripts of the rat cytochrome P450 2C24 gene: correlation with exon skipping. Proc Natl Acad Sci USA. 1996;93:6536–41.CrossRefPubMedPubMedCentral
42.
43.
44.
Meng X, Li X, Zhang P, Wang J, Zhou Y, Chen M. Circular RNA: an emerging key player in RNA world. Brief Bioinform. 2016:1–11.
45.
46.
47.
48.
Li J, Yang J, Zhou P, Le Y, Zhou C, Wang S, Xu D, Lin HK, Gong Z. Circular RNAs in cancer: novel insights into origins, properties, functions and implications. Am J Cancer Res. 2015;5:472–80.PubMedPubMedCentral
49.
Jiang L, Liu X, Chen Z, Jin Y, Heidbreder CE, Kolokythas A, Wang A, Dai Y, Zhou X. MicroRNA-7 targets IGF1R (insulin-like growth factor 1 receptor) in tongue squamous cell carcinoma cells. Biochem J. 2010;432:199–205.CrossRefPubMedPubMedCentral
50.
Zhao X, Dou W, He L, Liang S, Tie J, Liu C, Li T, Lu Y, Mo P, Shi Y, Wu K, Nie Y, Fan D. MicroRNA-7 functions as an anti-metastatic microRNA in gastric cancer by targeting insulinlike growth factor-1 receptor. Oncogene. 2013;32:1363–72.CrossRefPubMed
51.
Kong X, Li G, Yuan Y, He Y, Wu X, Zhang W, Wu Z, Chen T, Wu W, Lobie PE, Zhu T. MicroRNA-7 inhibits epithelial-to-mesenchymal transition and metastasis of breast cancer cells via targeting FAK expression. PLoS One. 2012;7:e41523.CrossRefPubMedPubMedCentral
52.
Wu DG, Wang YY, Fan LG, Luo H, Han B, Sun LH, Wang XF, Zhang JX, Cao L, Wang XR, You YP, Liu N. MicroRNA-7 regulates glioblastoma cell invasion via targeting focal adhesion kinase expression. Chin Med J (Engl). 2011;124:2616–21.
53.
Lu D, Xu AD. Mini review: circular RNAs as potential clinical biomarkers for disorders in the central nervous system. Front Genet. 2016;7(53)
54.
Wang K, Long B, Liu F, Wang JX, Liu CY, Zhao B, Zhou LY, Sun T, Wang M, Yu T, Gong Y, Liu J, Dong YH, Li N, Li PF. A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. Eur Heart J. 2016;37:2602–11.CrossRefPubMed
55.
56.
Militello G, Weirick T, John D, Döring C, Dimmeler S, Uchida S. Screening and validation of lncRNAs and circRNAs as miRNA sponges. Brief Bioinform. 2016:1–9.
57.
You X, Vlatkovic I, Babic A, Will T, Epstein I, Tushev G, Akbalik G, Wang M, Glock C, Quedenau C, Wang X, Hou J, Liu H, Sun W, Sambandan S, Chen T, Schuman EM, Chen W. Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nat Neurosci. 2015;18:603–10.CrossRefPubMedPubMedCentral
58.
Li B, Zhang XQ, Liu SR, Liu S, Sun WJ, Lin Q, Luo YX, Zhou KR, Zhang CM, Tan YY, Yang JH, Qu LH. Discovering the Interactions between Circular RNAs and RNA-binding Proteins from CLIP-seq Data using circScan. bioRxiv. 2017:115980.
59.
Chao CW, Chan DC, Kuo A, Leder P. The mouse formin (Fmn) gene: abundant circular RNA transcripts and gene targeted deletion analysis. Mol Med. 1998;4:614–28.PubMedPubMedCentral
60.
Kos A, Dijkema R, Arnberg AC, van der Meide PH, Schellekens H. The hepatitis delta (δ) virus possesses a circular RNA. Nature. 1986;323:558–60.CrossRefPubMed
61.
Granados-Riveron JT, Aquino-Jarquin G. The complexity of the translation ability of circRNAs. Biochim Biophys Acta. 2016;1859:1245–51.CrossRefPubMed
62.
Anderson DM, Anderson KM, Chang CL, Makarewich CA, Nelson BR, McAnally JR, Kasaragod P, Shelton JM, Liou J, Bassel-Duby R, Olson EN. A micropeptide encoded by a putative long noncoding RNA regulates muscle performance. Cell. 2015;160:595–606.CrossRefPubMedPubMedCentral
63.
Bazzini AA, Johnstone TG, Christiano R, Mackowiak SD, Obermayer B, Fleming ES, Vejnar CE, Lee MT, Rajewsky N, Walther TC, Giraldez AJ. Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation. EMBO J. 2014;33:981–93.CrossRefPubMedPubMedCentral
64.
65.
Abe N, Matsumoto K, Nishihara M, Nakano Y, Shibata A, Maruyama H, Shuto S, Matsuda A, Yoshida M, Ito Y, Abe H. Rolling circle translation of circular RNA in living human cells. Sci Rep. 2015;5(16435)
66.
Yang Y, Fan X, Mao M, Song X, Wu P, Zhang Y, Jin Y, Yang Y, Chen L, Wang Y, Wong CCL, Xiao X, Wang Z. Extensive translation of circular RNAs driven by N6-methyladenosine. Cell Res. 2017;27:626–41.CrossRefPubMedPubMedCentral
67.
Pamudurti NR, Bartok O, Jens M, Ashwal-Fluss R, Stottmeister C, Ruhe L, Hanan M, Wyler E, Perez-Hernandez D, Ramberger E, Shenzis S, Samson M, Dittmar G, Landthaler M, Chekulaeva M, Rajewsky N, Kadener S. Translation of circRNAs. Mol Cell. 2017;66:9–21.CrossRefPubMedPubMedCentral
68.
Legnini I, Di Timoteo G, Rossi F, Morlando M, Briganti F, Sthandier O, Fatica A, Santini T, Andronache A, Wade M, Laneve P, Rajewsky N, Bozzoni I. Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis. Mol Cell. 2017;66:22–37.CrossRefPubMedPubMedCentral
69.
Gardner EJ, Nizami ZF, Talbot CC, Gall JG. Stable intronic sequence RNA (sisRNA), a new class of noncoding RNA from the oocyte nucleus of Xenopus Tropicalis. Genes Dev. 2012;26:2550–9.CrossRefPubMedPubMedCentral
70.
71.
Fan X, Zhang X, Wu X, Guo H, Hu Y, Tang F, Huang Y. Single-cell RNA-seq transcriptome analysis of linear and circular RNAs in mouse preimplantation embryos. Genome Biol. 2015;16(148)
72.
Zhang C, Gao L, Xu EY. LncRNA, a new component of expanding RNA-protein regulatory network important for animal sperm development. Semin Cell Dev Biol. 2016;59:110–7.CrossRefPubMed
73.
Dumesic DA, Meldrum DR, Katz-Jaffe MG, Krisher RL, Schoolcraft WB. Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health. Fertil Steril. 2015;103:303–16.CrossRefPubMed
74.
Moreno JM, Nunez MJ, Quinonero A, Martinez S, de la Orden M, Simon C, Pellicer A, Díaz-García C, Domínguez F. Follicular fluid and mural granulosa cells microRNA profiles vary in in vitro fertilization patients depending on their age and oocyte maturation stage. Fertil Steril. 2015;104:1037–46.CrossRefPubMed
75.
Hamel M, Dufort I, Robert C, Gravel C, Leveille MC, Leader A, Sirard MA. Identification of differentially expressed markers in human follicular cells associated with competent oocytes. Hum Reprod. 2008;23:1118–27.CrossRefPubMed
76.
Hamel M, Dufort I, Robert C, Leveille MC, Leader A, Sirard MA. Genomic assessment of follicular marker genes as pregnancy predictors for human IVF. Mol Hum Reprod. 2010;16:87–96.CrossRefPubMed
77.
Cheng J, Huang J, Yuan S, Zhou S, Yan W, Shen W, Chen Y, Xia X, Luo A, Zhu D, Wang S. Circular RNA expression profiling of human granulosa cells during maternal aging reveals novel transcripts associated with assisted reproductive technology outcomes. PLoS One. 2017;12:e0177888.CrossRefPubMedPubMedCentral
78.
79.
Luk AC, Chan WY, Rennert OM, Lee TL. Long noncoding RNAs in spermatogenesis: insights from recent highthroughput transcriptome studies. Reproduction (Cambridge, England). 2014;147:R131–41.CrossRef
80.
Bettegowda A, Wilkinson MF. Transcription and post-transcriptional regulation of spermatogenesis. Philos Trans R Soc Lond Ser B Biol Sci. 2010;365:1637–51.CrossRef
81.
82.
Lin X, Han M, Cheng L, Chen J, Zhang Z, Shen T, Wang M, Wen B, Ni T, Han C. Expression dynamics, relationships, and transcriptional regulations of diverse transcripts in mouse spermatogenic cells. RNA Biol. 2016;13:1011–24.CrossRefPubMedPubMedCentral
83.
84.
Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A, Rinn JL. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Gen Dev. 2011;25:1915–27.CrossRef
85.
Zaphiropoulos PG. Exon skipping and circular RNA formation in transcripts of the human cytochrome P-450 2C18 gene in epidermis and of the rat androgen binding protein gene in testis. Mol Cell Biol. 1997;17:2985–93.CrossRefPubMedPubMedCentral
86.
Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, Smith MJ, Foster JW, Frischauf AM, Lovell-Badge R, Gwdfellow PN. A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature. 1990;346:240–4.CrossRefPubMed
87.
Koopman P, Gubbay J, Vivian N, Goodfellow P, LovellBadge R. Male development of chromosomally female mice transgenic for Sry. Nature. 1991;357:117–21.CrossRef
88.
Capel B, Swain A, Nicolis S, Hacker A, Walter M, Koopman P, Goodfellow P, Lovell-Badge R. Circular transcripts of the testis-determining gene Sry in adult mouse testis. Cell. 1993;73:1019–30.CrossRefPubMed
89.
Harley VR, Jackson D, Hextall P, Hawkins JR, Berkovitz GD, Sockanathan S, Lovell-Badge R, Goodfellow PN. DNA binding activity of recombinant SRY from normal males and XY females. Science. 1992;255:453–8.CrossRefPubMed
90.
Dubin RA, Kazmi MA, Ostrer H. Inverted repeated are necessary for circularization of mouse testis Sry transcript. Gene. 1995;167:245–8.CrossRefPubMed
91.
Hale BJ, Yang CX, Ross JW. Small RNA regulation of reproductive function. Mol Reprod Dev. 2014;81:148–59.CrossRefPubMed
92.
Liang Y, Ridzon D, Wong L, Chen C. Characterization Of microRNA expression profiles in normal human tissues. BMC Genomics. 2017;8:166.CrossRef
93.
94.
Wang W, Feng L, Zhang H, Hachy S, Satohisa S, Laurent LC, Parast M, Zheng J, Chen DB. Preeclampsia up-regulates angiogenesis-associated MicroRNA (i.E., miR-17, −20a, and -20b) that target ephrin-B2 and EPHB4 in human placenta. J Clin Endocrinol Metab. 2012;97:E1051–9.CrossRefPubMedPubMedCentral
95.
Zhang YG, Yang HL, Long Y, Li WL. Circular RNA in blood corpuscles combined with plasma protein factor for early prediction of pre-eclampsia. BJOG Int J Obstet Gynaecol. 2016;123:2113–8.CrossRef
96.
Bachmayr-Heyda A, Reiner AT, Auer K, Sukhbaatar N, Aust S, Bachleitner-Hofmann T, Mesteri I, Grunt TW, Zeillinger R, Pils D. Correlation of circular RNA abundance with proliferation–exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues. Sci Rep. 2015;5(8057)
97.
Memczak S, Papavasileiou P, Peters O, Rajewsky N. Identification and characterization of circular RNAs as a new class of putative biomarkers in human blood. PLoS One. 2015;10:e0141214.CrossRefPubMedPubMedCentral
98.
Ahmed I, Karedath T, Andrews SS, Al-Azwani IK, Mohamoud YA, Querleu D, Rafii A, Malek JA. Altered expression pattern of circular RNAs in primary and metastatic sites of epithelial ovarian carcinoma. Oncotarget. 2016;7:36366.PubMedPubMedCentral
99.
Advani SJ, Camargo MF, Seguin L, Mielgo A, Anand S, Hicks AM, Aguilera J, Franovic A, Weis SM, Cheresh DA. Kinase-independent role for CRAF-driving tumour radioresistance via CHK2. Nat Commun. 2015;6:8154.CrossRefPubMedPubMedCentral
100.
Fischer JW, AKL L. CircRNAs: A regulator of cellular stress. Crit Rev Biochem Mol Biol. 2017;52:220–33.CrossRefPubMed
101.
Jamnongjit M, Gill A, Hammes SR. Epidermal Growth factor receptor signaling is required for normal ovarian steroidogenesis and oocyte maturation. Proc Natl Acad Sci U S A. 2005;102:16257–62.CrossRefPubMedPubMedCentral
102.
Reddy SD, Ohshiro K, Rayala SK, Kumar R. MicroRNA-7, a homeobox D10 target, inhibits p21-activated kinase 1 and regulates its functions. Cancer Res. 2008;68:8195–200.CrossRefPubMedPubMedCentral
103.
Webster RJ, Giles KM, Price KJ, Zhang PM, Mattick JS, Leedman PJ. Regulation of epidermal growth factor receptor signaling in human cancer cells by microRNA-7. J Biol Chem. 2009;284:5731–41.CrossRefPubMed
104.
Zuo J, Wang Q, Zhu B, Luo Y, Gao L. Deciphering the roles of circRNAs on chilling injury in tomato. Biochem Biophys Res Commun. 2016;479:132–8.CrossRefPubMed
Metadata
Title
Circular RNAs: biogenesis, expression and their potential roles in reproduction
Authors
Guobo Quan
Julang Li
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2018
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-018-0381-4

Other articles of this Issue 1/2018

Journal of Ovarian Research 1/2018 Go to the issue

Research

Suitability assessment of baseline concentration of MMP3, TIMP3, HE4 and CA125 in the serum of patients with ovarian cancer

Research

Comparison of benign peritoneal fluid- and ovarian cancer ascites-derived extracellular vesicle RNA biomarkers

Research

Effects of myo-inositol plus alpha-lactalbumin in myo-inositol-resistant PCOS women

Research

Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors

Research

MicroRNA-424/503 cluster members regulate bovine granulosa cell proliferation and cell cycle progression by targeting SMAD7 gene through activin signalling pathway

Research

A protocol to isolate and qualify purified human preantral follicles in cases of acute leukemia, for future clinical applications