Endocrinology2013; 154(6); 2174-2187; doi: 10.1210/en.2012-2256

The absence of ER-β results in altered gene expression in ovarian granulosa cells isolated from in vivo preovulatory follicles.

Abstract: Determining the spatial and temporal expression of genes involved in the ovulatory pathway is critical for the understanding of the role of each estrogen receptor in the modulation of folliculogenesis and ovulation. Estrogen receptor (ER)-β is highly expressed in ovarian granulosa cells, and mice lacking ER-β are subfertile due to inefficient ovulation. Previous work has focused on isolated granulosa cells or cultured follicles and, although informative, provides confounding results due to the heterogeneous cell types present including granulosa and theca cells and oocytes and exposure to in vitro conditions. Herein we isolated preovulatory granulosa cells from wild-type (WT) and ERβ-null mice using laser capture microdissection to examine the genomic transcriptional response downstream of pregnant mare serum gonadotropin (mimicking FSH) and pregnant mare serum gonadotropin/human chorionic gonadotropin (mimicking LH) stimulation. This allows for a direct comparison of in vivo granulosa cells at the same stage of development from both WT and ERβ-null ovaries. ERβ-null granulosa cells showed altered expression of genes known to be regulated by FSH (Akap12 and Runx2) as well as not previously reported (Arnt2 and Pou5f1) in WT granulosa cells. Our analysis also identified 304 genes not previously associated with ERβ in granulosa cells. LH-responsive genes including Abcb1b and Fam110c show reduced expression in ERβ-null granulosa cells; however, novel genes including Rassf2 and Megf10 were also identified as being downstream of LH signaling in granulosa cells. Collectively, our data suggest that granulosa cells from ERβ-null ovaries may not be appropriately differentiated and are unable to respond properly to gonadotropin stimulation.
Publication Date: 2013-04-11 PubMed ID: 23580569PubMed Central: PMC3740481DOI: 10.1210/en.2012-2256Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Research Support
  • N.I.H.
  • Intramural

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigated the role of estrogen receptor (ER)β in the expression of specific genes in ovarian granulosa cells, vital for the ovulatory process. The study found that the absence of ERβ alters the expression of genes related to folliculogenesis and ovulation, potentially impeding the cells’ ability to respond to gonadotropin stimulation.

Methodology

  • The study utilized granulosa cells isolated from the ovaries of both wild-type (WT) and ERβ-null (without ERβ) mice.
  • These cells were isolated using laser capture microdissection, allowing for precise selection of cell types, and reducing confounding factors that previous studies might have encountered due to mixing of cell types or in vitro conditions.
  • The granulosa cells were stimulated with pregnant mare serum gonadotropin, which mimics follicle-stimulating hormone (FSH), and a combination of this with human chorionic gonadotropin (mimicking luteinizing hormone, LH).

Findings

  • The research found that the absence of ERβ in granulosa cells alters the expression of several genes. Some of these altered genes are known to be regulated by FSH, such as Akap12 and Runx2, while others, including Arnt2 and Pou5f1, hadn’t been previously reported in WT granulosa cells.
  • The study also identified over 300 genes associated with ERβ.
  • LH-responsive genes, like Abcb1b and Fam110c, were found to have reduced expression in ERβ-null granulosa cells. Nonetheless, novel genes, such as Rassf2 and Megf10, were also identified as being impacted by LH in granulosa cells.
  • These results indicate that ERβ-null granulosa cells might not be appropriately differentiated, and may not respond properly to gonadotropin stimulation. This could lead to issues with ovulation, and further, to subfertility.

Conclusion

  • This research provides a clearer depiction of the importance of ERβ in folliculogenesis and ovulation by mapping the genes influenced by this receptor.
  • It also gives leads for future research, especially concerning the novel genes identified during the study.
  • The understanding of how the absence of ERβ impacts gene expression could shed light on fertility issues and can potentially lead to effective therapeutic interventions for subfertility.

Cite This Article

APA
Binder AK, Rodriguez KF, Hamilton KJ, Stockton PS, Reed CE, Korach KS. (2013). The absence of ER-β results in altered gene expression in ovarian granulosa cells isolated from in vivo preovulatory follicles. Endocrinology, 154(6), 2174-2187. https://doi.org/10.1210/en.2012-2256

Publication

ISSN: 1945-7170
NlmUniqueID: 0375040
Country: United States
Language: English
Volume: 154
Issue: 6
Pages: 2174-2187

Researcher Affiliations

Binder, April K
  • National Institute of Environmental Health Sciences, Laboratory of Reproduction and Developmental Toxicology, 111 TW Alexander Drive, MD B3-02, Research Triangle Park, North Carolina 27709, USA.
Rodriguez, Karina F
    Hamilton, Katherine J
      Stockton, Patricia S
        Reed, Casey E
          Korach, Kenneth S

            MeSH Terms

            • Animals
            • Cells, Cultured
            • Chorionic Gonadotropin / pharmacology
            • Estrogen Receptor beta / deficiency
            • Estrogen Receptor beta / genetics
            • Female
            • Gene Expression Profiling
            • Gonadotropins, Equine / pharmacology
            • Granulosa Cells / drug effects
            • Granulosa Cells / metabolism
            • Horses
            • Humans
            • Mice
            • Mice, Knockout
            • Oligonucleotide Array Sequence Analysis
            • Ovarian Follicle / cytology
            • Ovarian Follicle / metabolism
            • Ovary / cytology
            • Ovary / metabolism
            • Ovulation / genetics
            • Pregnancy
            • Time Factors

            Grant Funding

            • Z01 ES070065 / Intramural NIH HHS

            References

            This article includes 49 references
            1. Richards JS, Fitzpatrick SL, Clemens JW, Morris JK, Alliston T, Sirois J. Ovarian cell differentiation: a cascade of multiple hormones, cellular signals, and regulated genes.. Recent Prog Horm Res 1995;50:223-54.
            2. Knecht M, Brodie AM, Catt KJ. Aromatase inhibitors prevent granulosa cell differentiation: an obligatory role for estrogens in luteinizing hormone receptor expression.. Endocrinology 1985 Sep;117(3):1156-61.
              pubmed: 2990868doi: 10.1210/endo-117-3-1156google scholar: lookup
            3. Kessel B, Liu YX, Jia XC, Hsueh AJ. Autocrine role of estrogens in the augmentation of luteinizing hormone receptor formation in cultured rat granulosa cells.. Biol Reprod 1985 Jun;32(5):1038-50.
              pubmed: 2990583doi: 10.1095/biolreprod32.5.1038google scholar: lookup
            4. Richards JS, Russell DL, Robker RL, Dajee M, Alliston TN. Molecular mechanisms of ovulation and luteinization.. Mol Cell Endocrinol 1998 Oct 25;145(1-2):47-54.
              pubmed: 9922098doi: 10.1016/s0303-7207(98)00168-3google scholar: lookup
            5. Espey LL, Richards JS. Temporal and spatial patterns of ovarian gene transcription following an ovulatory dose of gonadotropin in the rat.. Biol Reprod 2002 Dec;67(6):1662-70.
              pubmed: 12444039doi: 10.1095/biolreprod.102.005173google scholar: lookup
            6. Jefferson WN, Couse JF, Banks EP, Korach KS, Newbold RR. Expression of estrogen receptor beta is developmentally regulated in reproductive tissues of male and female mice.. Biol Reprod 2000 Feb;62(2):310-7.
              pubmed: 10642567doi: 10.1095/biolreprod62.2.310google scholar: lookup
            7. Krege JH, Hodgin JB, Couse JF, Enmark E, Warner M, Mahler JF, Sar M, Korach KS, Gustafsson JA, Smithies O. Generation and reproductive phenotypes of mice lacking estrogen receptor beta.. Proc Natl Acad Sci U S A 1998 Dec 22;95(26):15677-82.
              pmc: PMC28103pubmed: 9861029doi: 10.1073/pnas.95.26.15677google scholar: lookup
            8. Couse JF, Yates MM, Deroo BJ, Korach KS. Estrogen receptor-beta is critical to granulosa cell differentiation and the ovulatory response to gonadotropins.. Endocrinology 2005 Aug;146(8):3247-62.
              pubmed: 15831568doi: 10.1210/en.2005-0213google scholar: lookup
            9. Emmen JM, Couse JF, Elmore SA, Yates MM, Kissling GE, Korach KS. In vitro growth and ovulation of follicles from ovaries of estrogen receptor (ER){alpha} and ER{beta} null mice indicate a role for ER{beta} in follicular maturation.. Endocrinology 2005 Jun;146(6):2817-26.
              pubmed: 15731357doi: 10.1210/en.2004-1108google scholar: lookup
            10. Rodriguez KF, Couse JF, Jayes FL, Hamilton KJ, Burns KA, Taniguchi F, Korach KS. Insufficient luteinizing hormone-induced intracellular signaling disrupts ovulation in preovulatory follicles lacking estrogen receptor-{beta}.. Endocrinology 2010 Jun;151(6):2826-34.
              pmc: PMC2875826pubmed: 20378682doi: 10.1210/en.2009-1446google scholar: lookup
            11. Liu J, Park ES, Jo M. Runt-related transcription factor 1 regulates luteinized hormone-induced prostaglandin-endoperoxide synthase 2 expression in rat periovulatory granulosa cells.. Endocrinology 2009 Jul;150(7):3291-300.
              pmc: PMC2703554pubmed: 19342459doi: 10.1210/en.2008-1527google scholar: lookup
            12. Fu M, Chen X, Yan J, Lei L, Jin S, Yang J, Song X, Zhang M, Xia G. Luteinizing hormone receptors expression in cumulus cells closely related to mouse oocyte meiotic maturation.. Front Biosci 2007 Jan 1;12:1804-13.
              pubmed: 17127422doi: 10.2741/2189google scholar: lookup
            13. McNatty KP, Juengel JL, Reader KL, Lun S, Myllymaa S, Lawrence SB, Western A, Meerasahib MF, Mottershead DG, Groome NP, Ritvos O, Laitinen MP. Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function.. Reproduction 2005 Apr;129(4):473-80.
              pubmed: 15798022doi: 10.1530/rep.1.0511google scholar: lookup
            14. Hewitt SC, Kissling GE, Fieselman KE, Jayes FL, Gerrish KE, Korach KS. Biological and biochemical consequences of global deletion of exon 3 from the ER alpha gene.. FASEB J 2010 Dec;24(12):4660-7.
              pmc: PMC2992373pubmed: 20667977doi: 10.1096/fj.10-163428google scholar: lookup
            15. Deroo BJ, Rodriguez KF, Couse JF, Hamilton KJ, Collins JB, Grissom SF, Korach KS. Estrogen receptor beta is required for optimal cAMP production in mouse granulosa cells.. Mol Endocrinol 2009 Jul;23(7):955-65.
              pmc: PMC2703605pubmed: 19324971doi: 10.1210/me.2008-0213google scholar: lookup
            16. Winuthayanon W, Piyachaturawat P, Suksamrarn A, Ponglikitmongkol M, Arao Y, Hewitt SC, Korach KS. Diarylheptanoid phytoestrogens isolated from the medicinal plant Curcuma comosa: biologic actions in vitro and in vivo indicate estrogen receptor-dependent mechanisms.. Environ Health Perspect 2009 Jul;117(7):1155-61.
              pmc: PMC2717144pubmed: 19654927doi: 10.1289/ehp.0900613google scholar: lookup
            17. Zalewski A, Cecchini EL, Deroo BJ. Expression of extracellular matrix components is disrupted in the immature and adult estrogen receptor u03b2-null mouse ovary.. PLoS One 2012;7(1):e29937.
            18. Nagaraja AK, Middlebrook BS, Rajanahally S, Myers M, Li Q, Matzuk MM, Pangas SA. Defective gonadotropin-dependent ovarian folliculogenesis and granulosa cell gene expression in inhibin-deficient mice.. Endocrinology 2010 Oct;151(10):4994-5006.
              pmc: PMC2946151pubmed: 20739397doi: 10.1210/en.2010-0428google scholar: lookup
            19. Carletti MZ, Christenson LK. Rapid effects of LH on gene expression in the mural granulosa cells of mouse periovulatory follicles.. Reproduction 2009 May;137(5):843-55.
              pmc: PMC3118672pubmed: 19225042doi: 10.1530/REP-08-0457google scholar: lookup
            20. Fan HY, Liu Z, Johnson PF, Richards JS. CCAAT/enhancer-binding proteins (C/EBP)-u03b1 and -u03b2 are essential for ovulation, luteinization, and the expression of key target genes.. Mol Endocrinol 2011 Feb;25(2):253-68.
              pmc: PMC3386543pubmed: 21177758doi: 10.1210/me.2010-0318google scholar: lookup
            21. Escamilla-Hernandez R, Little-Ihrig L, Orwig KE, Yue J, Chandran U, Zeleznik AJ. Constitutively active protein kinase A qualitatively mimics the effects of follicle-stimulating hormone on granulosa cell differentiation.. Mol Endocrinol 2008 Aug;22(8):1842-52.
              pmc: PMC2725770pubmed: 18535249doi: 10.1210/me.2008-0103google scholar: lookup
            22. Racki WJ, Richter JD. CPEB controls oocyte growth and follicle development in the mouse.. Development 2006 Nov;133(22):4527-37.
              pubmed: 17050619doi: 10.1242/dev.02651google scholar: lookup
            23. Li F, Jang H, Puttabyatappa M, Jo M, Curry TE Jr. Ovarian FAM110C (family with sequence similarity 110C): induction during the periovulatory period and regulation of granulosa cell cycle kinetics in rats.. Biol Reprod 2012 Jun;86(6):185.
            24. Hunzicker-Dunn ME, Lopez-Biladeau B, Law NC, Fiedler SE, Carr DW, Maizels ET. PKA and GAB2 play central roles in the FSH signaling pathway to PI3K and AKT in ovarian granulosa cells.. Proc Natl Acad Sci U S A 2012 Oct 30;109(44):E2979-88.
              pmc: PMC3497822pubmed: 23045700doi: 10.1073/pnas.1205661109google scholar: lookup
            25. Barnett KR, Tomic D, Gupta RK, Babus JK, Roby KF, Terranova PF, Flaws JA. The aryl hydrocarbon receptor is required for normal gonadotropin responsiveness in the mouse ovary.. Toxicol Appl Pharmacol 2007 Aug 15;223(1):66-72.
              pmc: PMC1987310pubmed: 17594909doi: 10.1016/j.taap.2007.05.014google scholar: lookup
            26. Maman E, Yung Y, Cohen B, Konopnicki S, Dal Canto M, Fadini R, Kanety H, Kedem A, Dor J, Hourvitz A. Expression and regulation of sFRP family members in human granulosa cells.. Mol Hum Reprod 2011 Jul;17(7):399-404.
              pubmed: 21307090doi: 10.1093/molehr/gar010google scholar: lookup
            27. Rajkovic A, Pangas SA, Ballow D, Suzumori N, Matzuk MM. NOBOX deficiency disrupts early folliculogenesis and oocyte-specific gene expression.. Science 2004 Aug 20;305(5687):1157-9.
              pubmed: 15326356doi: 10.1126/science.1099755google scholar: lookup
            28. Li F, Liu J, Jo M, Curry TE Jr. A role for nuclear factor interleukin-3 (NFIL3), a critical transcriptional repressor, in down-regulation of periovulatory gene expression.. Mol Endocrinol 2011 Mar;25(3):445-59.
              pmc: PMC3045738pubmed: 21212137doi: 10.1210/me.2010-0250google scholar: lookup
            29. O'Shaughnessy PJ, Mannan MA. Development of cytochrome P-450 side chain cleavage mRNA levels in neonatal ovaries of normal and hypogonadal (hpg) mice.. Mol Cell Endocrinol 1994 Sep;104(2):133-8.
              pubmed: 7527351doi: 10.1016/0303-7207(94)90115-5google scholar: lookup
            30. Chen ZH, Hurh YJ, Na HK, Kim JH, Chun YJ, Kim DH, Kang KS, Cho MH, Surh YJ. Resveratrol inhibits TCDD-induced expression of CYP1A1 and CYP1B1 and catechol estrogen-mediated oxidative DNA damage in cultured human mammary epithelial cells.. Carcinogenesis 2004 Oct;25(10):2005-13.
              pubmed: 15142886doi: 10.1093/carcin/bgh183google scholar: lookup
            31. Horling K, Santos AN, Fischer B. The AhR is constitutively activated and affects granulosa cell features in the human cell line KGN.. Mol Hum Reprod 2011 Feb;17(2):104-14.
              pubmed: 20823264doi: 10.1093/molehr/gaq074google scholar: lookup
            32. Heindel JJ, Sneeden J, Powell CJ, Davis B, Culler MD. A novel hypothalamic peptide, pituitary adenylate cyclase-activating peptide, regulates the function of rat granulosa cells in vitro.. Biol Reprod 1996 Mar;54(3):523-30.
              pubmed: 8835372doi: 10.1095/biolreprod54.3.523google scholar: lookup
            33. Conneely OM. Progesterone receptors and ovulation.. Handb Exp Pharmacol 2010;(198):37-44.
              pubmed: 20839085doi: 10.1007/978-3-642-02062-9_3google scholar: lookup
            34. Le JA, Wilson HM, Shehu A, Mao J, Devi YS, Halperin J, Aguilar T, Seibold A, Maizels E, Gibori G. Generation of mice expressing only the long form of the prolactin receptor reveals that both isoforms of the receptor are required for normal ovarian function.. Biol Reprod 2012 Mar;86(3):86.
            35. Nagyova E, Camaioni A, Scsukova S, Mlynarcikova A, Prochazka R, Nemcova L, Salustri A. Activation of cumulus cell SMAD2/3 and epidermal growth factor receptor pathways are involved in porcine oocyte-cumulus cell expansion and steroidogenesis.. Mol Reprod Dev 2011 Jun;78(6):391-402.
              pubmed: 21520325doi: 10.1002/mrd.21312google scholar: lookup
            36. Elvin JA, Clark AT, Wang P, Wolfman NM, Matzuk MM. Paracrine actions of growth differentiation factor-9 in the mammalian ovary.. Mol Endocrinol 1999 Jun;13(6):1035-48.
              pubmed: 10379900doi: 10.1210/mend.13.6.0310google scholar: lookup
            37. Richards JS. Ovulation: new factors that prepare the oocyte for fertilization.. Mol Cell Endocrinol 2005 Apr 29;234(1-2):75-9.
              pubmed: 15836955doi: 10.1016/j.mce.2005.01.004google scholar: lookup
            38. McNatty KP, Heath DA, Hudson NL, Reader KL, Quirke L, Lun S, Juengel JL. The conflict between hierarchical ovarian follicular development and superovulation treatment.. Reproduction 2010 Aug;140(2):287-94.
              pubmed: 20501789doi: 10.1530/REP-10-0165google scholar: lookup
            39. Choi Y, Rajkovic A. Characterization of NOBOX DNA binding specificity and its regulation of Gdf9 and Pou5f1 promoters.. J Biol Chem 2006 Nov 24;281(47):35747-56.
              pubmed: 16997917doi: 10.1074/jbc.M604008200google scholar: lookup
            40. Richards JS, Pangas SA. The ovary: basic biology and clinical implications.. J Clin Invest 2010 Apr;120(4):963-72.
              pmc: PMC2846061pubmed: 20364094doi: 10.1172/JCI41350google scholar: lookup
            41. Boyer A, Goff AK, Boerboom D. WNT signaling in ovarian follicle biology and tumorigenesis.. Trends Endocrinol Metab 2010 Jan;21(1):25-32.
              pubmed: 19875303doi: 10.1016/j.tem.2009.08.005google scholar: lookup
            42. Gordon MD, Nusse R. Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors.. J Biol Chem 2006 Aug 11;281(32):22429-33.
              pubmed: 16793760doi: 10.1074/jbc.R600015200google scholar: lookup
            43. Parakh TN, Hernandez JA, Grammer JC, Weck J, Hunzicker-Dunn M, Zeleznik AJ, Nilson JH. Follicle-stimulating hormone/cAMP regulation of aromatase gene expression requires beta-catenin.. Proc Natl Acad Sci U S A 2006 Aug 15;103(33):12435-40.
              pmc: PMC1533882pubmed: 16895991doi: 10.1073/pnas.0603006103google scholar: lookup
            44. Boerboom D, White LD, Dalle S, Courty J, Richards JS. Dominant-stable beta-catenin expression causes cell fate alterations and Wnt signaling antagonist expression in a murine granulosa cell tumor model.. Cancer Res 2006 Feb 15;66(4):1964-73.
              pubmed: 16488995doi: 10.1158/0008-5472.CAN-05-3493google scholar: lookup
            45. Mack EM, Smith JE, Kurz SG, Wood JR. cAMP-dependent regulation of ovulatory response genes is amplified by IGF1 due to synergistic effects on Akt phosphorylation and NF-u03baB transcription factors.. Reproduction 2012 Nov;144(5):595-602.
              pubmed: 22956516doi: 10.1530/REP-12-0225google scholar: lookup
            46. Conti M, Hsieh M, Park JY, Su YQ. Role of the epidermal growth factor network in ovarian follicles.. Mol Endocrinol 2006 Apr;20(4):715-23.
              pubmed: 16051667doi: 10.1210/me.2005-0185google scholar: lookup
            47. Kay JN, Chu MW, Sanes JR. MEGF10 and MEGF11 mediate homotypic interactions required for mosaic spacing of retinal neurons.. Nature 2012 Mar 11;483(7390):465-9.
              pmc: PMC3310952pubmed: 22407321doi: 10.1038/nature10877google scholar: lookup
            48. Sugiura K, Su YQ, Eppig JJ. Targeted suppression of Has2 mRNA in mouse cumulus cell-oocyte complexes by adenovirus-mediated short-hairpin RNA expression.. Mol Reprod Dev 2009 Jun;76(6):537-47.
              pmc: PMC2669700pubmed: 18951380doi: 10.1002/mrd.20971google scholar: lookup
            49. Hewitt SC, Li L, Grimm SA, Chen Y, Liu L, Li Y, Bushel PR, Fargo D, Korach KS. Research resource: whole-genome estrogen receptor u03b1 binding in mouse uterine tissue revealed by ChIP-seq.. Mol Endocrinol 2012 May;26(5):887-98.
              pmc: PMC3355558pubmed: 22446102doi: 10.1210/me.2011-1311google scholar: lookup

            Citations

            This article has been cited 31 times.
            1. Xue Y, Gong Y, Li X, Peng F, Ding G, Zhang Z, Shi J, Savul IS, Xu Y, Chen Q, Han L, Mao S, Sun Z. Sex differences in paternal arsenic-induced intergenerational metabolic effects are mediated by estrogen.. Cell Biosci 2023 Sep 10;13(1):165.
              doi: 10.1186/s13578-023-01121-4pubmed: 37691128google scholar: lookup
            2. Birgersson M, Indukuri R, Antonson P, Nalvarte I, Archer A, Williams C. ERu03b2 in Granulosa Cell Tumors and Its Clinical Potential.. Endocrinology 2023 Apr 17;164(6).
              doi: 10.1210/endocr/bqad063pubmed: 37075218google scholar: lookup
            3. Kluivers KB, Lince SL, Ruiz-Zapata AM, Post WM, Cartwright R, Kerkhof MH, Widomska J, De Witte W, Pecanka J, Kiemeney LA, Vermeulen SH, Goeman JJ, Allen-Brady K, Oosterwijk E, Poelmans G. Molecular Landscape of Pelvic Organ Prolapse Provides Insights into Disease Etiology.. Int J Mol Sci 2023 Mar 23;24(7).
              doi: 10.3390/ijms24076087pubmed: 37047060google scholar: lookup
            4. Lin X, Zhang K, Meng T. AKAP12 and RNF11 as Diagnostic Markers of Fibromyalgia and Their Correlation with Immune Infiltration.. Oxid Med Cell Longev 2022;2022:9033342.
              doi: 10.1155/2022/9033342pubmed: 36238643google scholar: lookup
            5. Liang Q, Peng J, Xu Z, Li Z, Jiang F, Ouyang L, Wu S, Fu C, Liu Y, Liu Y, Yan Y. Pan-cancer analysis of the prognosis and immunological role of AKAP12: A potential biomarker for resistance to anti-VEGF inhibitors.. Front Genet 2022;13:943006.
              doi: 10.3389/fgene.2022.943006pubmed: 36110213google scholar: lookup
            6. Dinh DT, Russell DL. Nuclear Receptors in Ovarian Function.. Adv Exp Med Biol 2022;1390:41-58.
              doi: 10.1007/978-3-031-11836-4_3pubmed: 36107312google scholar: lookup
            7. Kuan KKW, Saunders PTK. Female Reproductive Systems: Hormone Dependence and Receptor Expression.. Adv Exp Med Biol 2022;1390:21-39.
              doi: 10.1007/978-3-031-11836-4_2pubmed: 36107311google scholar: lookup
            8. Martu00ednez-Moro u00c1, Gonzu00e1lez-Brusi L, Lamas-Toranzo I, O'Callaghan E, Esteve-Codina A, Lonergan P, Bermejo-u00c1lvarez P. RNA-sequencing reveals genes linked with oocyte developmental potential in bovine cumulus cells.. Mol Reprod Dev 2022 Sep;89(9):399-412.
              doi: 10.1002/mrd.23631pubmed: 35802551google scholar: lookup
            9. Wei C, Liu X, Wang Q, Li Q, Xie M. Identification of Hypoxia Signature to Assess the Tumor Immune Microenvironment and Predict Prognosis in Patients with Ovarian Cancer.. Int J Endocrinol 2021;2021:4156187.
              doi: 10.1155/2021/4156187pubmed: 34950205google scholar: lookup
            10. Kawai T, Richards JS, Shimada M. Large-scale DNA demethylation occurs in proliferating ovarian granulosa cells during mouse follicular development.. Commun Biol 2021 Nov 25;4(1):1334.
              doi: 10.1038/s42003-021-02849-wpubmed: 34824385google scholar: lookup
            11. Lee EB, Chakravarthi VP, Wolfe MW, Rumi MAK. ERu03b2 Regulation of Gonadotropin Responses during Folliculogenesis.. Int J Mol Sci 2021 Sep 26;22(19).
              doi: 10.3390/ijms221910348pubmed: 34638689google scholar: lookup
            12. Li Z, Zhang M, Tian Y, Li Q, Huang X. Mesenchymal Stem Cells in Premature Ovarian Insufficiency: Mechanisms and Prospects.. Front Cell Dev Biol 2021;9:718192.
              doi: 10.3389/fcell.2021.718192pubmed: 34414193google scholar: lookup
            13. Kang Z, Bai Y, Lan X, Zhao H. Goat AKAP12: Indel Mutation Detection, Association Analysis With Litter Size and Alternative Splicing Variant Expression.. Front Genet 2021;12:648256.
              doi: 10.3389/fgene.2021.648256pubmed: 34093646google scholar: lookup
            14. Milner TA, Contoreggi NH, Yu F, Johnson MA, Wang G, Woods C, Mazid S, Van Kempen TA, Waters EM, McEwen BS, Korach KS, Glass MJ. Estrogen Receptor u03b2 Contributes to Both Hypertension and Hypothalamic Plasticity in a Mouse Model of Peri-Menopause.. J Neurosci 2021 Jun 16;41(24):5190-5205.
            15. Goodman WA, Bedoyan SM, Havran HL, Richardson B, Cameron MJ, Pizarro TT. Impaired estrogen signaling underlies regulatory T cell loss-of-function in the chronically inflamed intestine.. Proc Natl Acad Sci U S A 2020 Jul 21;117(29):17166-17176.
              doi: 10.1073/pnas.2002266117pubmed: 32632016google scholar: lookup
            16. Qasim H, McConnell BK. AKAP12 Signaling Complex: Impacts of Compartmentalizing cAMP-Dependent Signaling Pathways in the Heart and Various Signaling Systems.. J Am Heart Assoc 2020 Jul 7;9(13):e016615.
              doi: 10.1161/JAHA.120.016615pubmed: 32573313google scholar: lookup
            17. Brayboy LM, Knapik LO, Long S, Westrick M, Wessel GM. Ovarian hormones modulate multidrug resistance transporters in the ovary.. Contracept Reprod Med 2018;3:26.
              doi: 10.1186/s40834-018-0076-7pubmed: 30460040google scholar: lookup
            18. Novaira HJ, Negron AL, Graceli JB, Capellino S, Schoeffield A, Hoffman GE, Levine JE, Wolfe A, Wondisford FE, Radovick S. Impairments in the reproductive axis of female mice lacking estrogen receptor u03b2 in GnRH neurons.. Am J Physiol Endocrinol Metab 2018 Nov 1;315(5):E1019-E1033.
              doi: 10.1152/ajpendo.00173.2018pubmed: 30040478google scholar: lookup
            19. Hewitt SC, Korach KS. Estrogen Receptors: New Directions in the New Millennium.. Endocr Rev 2018 Oct 1;39(5):664-675.
              doi: 10.1210/er.2018-00087pubmed: 29901737google scholar: lookup
            20. Son J, Park Y, Chung SH. Epithelial oestrogen receptor u03b1 is dispensable for the development of oestrogen-induced cervical neoplastic diseases.. J Pathol 2018 Jun;245(2):147-152.
              doi: 10.1002/path.5069pubmed: 29532467google scholar: lookup
            21. Wang X, Mittal P, Castro CA, Rajkovic G, Rajkovic A. Med12 regulates ovarian steroidogenesis, uterine development and maternal effects in the mammalian egg.. Biol Reprod 2017 Jan 1;97(6):822-834.
              doi: 10.1093/biolre/iox143pubmed: 29126187google scholar: lookup
            22. Hamilton KJ, Hewitt SC, Arao Y, Korach KS. Estrogen Hormone Biology.. Curr Top Dev Biol 2017;125:109-146.
              doi: 10.1016/bs.ctdb.2016.12.005pubmed: 28527569google scholar: lookup
            23. Rumi MAK, Singh P, Roby KF, Zhao X, Iqbal K, Ratri A, Lei T, Cui W, Borosha S, Dhakal P, Kubota K, Chakraborty D, Vivian JL, Wolfe MW, Soares MJ. Defining the Role of Estrogen Receptor u03b2 in the Regulation of Female Fertility.. Endocrinology 2017 Jul 1;158(7):2330-2343.
              doi: 10.1210/en.2016-1916pubmed: 28520870google scholar: lookup
            24. Donoghue LJ, Neufeld TI, Li Y, Arao Y, Coons LA, Korach KS. Differential Activation of a Mouse Estrogen Receptor u03b2 Isoform (mERu03b22) with Endocrine-Disrupting Chemicals (EDCs).. Environ Health Perspect 2017 Apr;125(4):634-642.
              doi: 10.1289/EHP396pubmed: 27634370google scholar: lookup
            25. Lan D, Xiong X, Huang C, Mipam TD, Li J. Toward Understanding the Genetic Basis of Yak Ovary Reproduction: A Characterization and Comparative Analyses of Estrus Ovary Transcriptiome in Yak and Cattle.. PLoS One 2016;11(4):e0152675.
              doi: 10.1371/journal.pone.0152675pubmed: 27044040google scholar: lookup
            26. Hewitt SC, Winuthayanon W, Korach KS. What's new in estrogen receptor action in the female reproductive tract.. J Mol Endocrinol 2016 Feb;56(2):R55-71.
              doi: 10.1530/JME-15-0254pubmed: 26826253google scholar: lookup
            27. Cacioppo JA, Koo Y, Lin PC, Osmulski SA, Ko CD, Ko C. Generation of an estrogen receptor beta-iCre knock-in mouse.. Genesis 2016 Jan;54(1):38-52.
              doi: 10.1002/dvg.22911pubmed: 26663382google scholar: lookup
            28. El-Hayek S, Demeestere I, Clarke HJ. Follicle-stimulating hormone regulates expression and activity of epidermal growth factor receptor in the murine ovarian follicle.. Proc Natl Acad Sci U S A 2014 Nov 25;111(47):16778-83.
              doi: 10.1073/pnas.1414648111pubmed: 25385589google scholar: lookup
            29. Chronowska E. High-throughput analysis of ovarian granulosa cell transcriptome.. Biomed Res Int 2014;2014:213570.
              doi: 10.1155/2014/213570pubmed: 24711992google scholar: lookup
            30. Toda K, Hayashi Y, Yamashita A, Okabe M, Ono M, Saibara T. Aromatase-null mice expressing enhanced green fluorescent protein in germ cells provide a model system to assess estrogen-dependent ovulatory responses.. Transgenic Res 2014 Apr;23(2):293-302.
              doi: 10.1007/s11248-013-9771-ypubmed: 24272335google scholar: lookup
            31. Wardell JR, Hodgkinson KM, Binder AK, Seymour KA, Korach KS, Vanderhyden BC, Freiman RN. Estrogen responsiveness of the TFIID subunit TAF4B in the normal mouse ovary and in ovarian tumors.. Biol Reprod 2013 Nov;89(5):116.
              doi: 10.1095/biolreprod.113.111336pubmed: 24068106google scholar: lookup