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- Miguel Brieño-Enríquez, MD, PhD
Miguel Brieño-Enríquez, MD, PhD
Assistant Professor, Department of Obstetrics, Gynecology & Reproductive Sciences, Magee-Womens Research Institute
Over half a girl’s eggs die before she is even born, and the number of healthy eggs continue to decrease throughout her life. My lab and I are researching how we can reduce ovarian aging, keep women’s eggs healthy throughout their lives, so they can continue having healthy babies and improve their healthspan and lifespan.
Miguel Brieño-Enríquez, MD, PhD
Research in Brief
Research in the Brieño-Enríquez lab focuses on the regulation of gametogenesis in human, mouse and naked mole-rat and, more specifically, the fundamental mechanisms that are required to produce viable germ cells. Our studies include the analysis of all the different stages of germs cells including primordial germ cells (PGCs), spermatocytes, oocytes, as well as how age affects them.
Current Projects
PROTECTION OF OVARIAN RESERVE AND REPRODUCTIVE AGING IN MAMMALS (THE NAKED MOLE-RAT PROJECT)
During the last 5 years, Brieño-Enriquez Lab developed the naked mole-rat (NMR) as a model in ovarian development and reproductive aging. Brieño-Enriquez lab showed the presence of germ cells that mitotically divide postnatally at early postnatal ages as well as in reproductively active females (queens). We also showed meiotic initiation postnatally and the presence of germ cells at meiotic prophase in adults. Using in vitro approaches, our lab was able to expand naked mole-rat germ cells population and generate follicles. Our long-term goal is to test his overarching hypothesis that gene expression, epigenetic clock, and chromatin structure in the NMR can be hijacked for use in other species, allowing us to regulate the establishment and maintenance of the ovarian reserve, oocyte quality, and reproductive longevity.
Using Naked Mole-Rat Lymph Nodes as Bioreactor for Ovarian Rejuvenation
Up to know, there is not treatment for menopause, this new approach of using the lymph node as an in vivo bioreactor in which to regenerate functional ovaries may be beneficial to improve female overall health after menopause reducing the risk of cancer, cardiovascular diseases, osteoporosis, overall, extending the healthspan. In this project we will test the hypothesis that when transplanted directly into the lymph nodes of NMR, PGCs, theca and granulosa cells engraft and show ectopic ovary functions in vivo, providing a strong evidence-based proof of principle for the develop of novel therapies for ovarian rejuvenation beyond just reproduction.
TRANSGENERATIONAL EPIGENETIC EFFECTS, PGCS AND NON-CODING RNAS:
In mammals, Primordial Germ Cells (PGCs) give rise to the germ cell pool during fetal development. We investigate whether prenatal exposure to environmental toxicants/drugs, such as endocrine disruptors, alter PGC differentiation, alter development of the germline, and/or induce transgenerational epigenetic disorders.
Selected Publications
- Zanini BM, Ávila BM, Hense JD, Garcia DN, Ashiqueali S, Alves PIC, Oliveira TL, Collares TV, Brieño-Enríquez MA, Mason JB, Masternak MM, Schneider A. Extracellular vesicles from cyclic mice modulate liver transcriptome in estroupause mice independent of age. Mol Cell Endocrinol. 2025 Apr 15;600:112508. doi: 10.1016/j.mce.2025.112508. Epub 2025 Feb 25. PubMed PMID: 40015357; PubMed Central PMCID: PMC11892024.
- Rosado GM, Martinez-Marchal A, Faykoo-Martinez M, Holmes MM, Brieño-Enríquez MA. Naked mole rat ovaries allow investigation of ovarian reserve, in vitro germ cell expansion, and oocyte in vitro maturation within a single sample. Reproduction. 2024 May 1;167(5). doi: 10.1530/REP-23-0459. Print 2024 May 1. PubMed PMID: 38457920; PubMed Central PMCID: PMC11023744.
- Walsh PT, Martínez-Marchal A, Brieño-Enríquez MA. Culture of the Intact Postnatal Naked Mole-Rat Ovary: From Meiotic Prophase to Single-Cell RNASeq. Methods Mol Biol. 2024;2818:179-194. doi: 10.1007/978-1-0716-3906-1_12. PubMed PMID: 39126475.
- Barreñada O, González-Sanz S, López-Palacios A, Carballo JA, Del Mazo J, Brieño-Enríquez MA. Analysis of Meiotic Progression by Ex Vivo Culture of Mouse Embryonic Ovaries. Methods Mol Biol. 2024;2818:133-145. doi: 10.1007/978-1-0716-3906-1_8. PubMed PMID: 39126471.
- Brieño-Enríquez MA, Faykoo-Martinez M, Goben M, Grenier JK, McGrath A, Prado AM, Sinopoli J, Wagner K, Walsh PT, Lopa SH, Laird DJ, Cohen PE, Wilson MD, Holmes MM, Place NJ. Postnatal oogenesis leads to an exceptionally large ovarian reserve in naked mole-rats. Nat Commun. 2023 Feb 21;14(1):670. doi: 10.1038/s41467-023-36284-8. PubMed PMID: 36810851; PubMed Central PMCID: PMC9944903.
- Brieño-Enríquez MA. Characterization of the Postnatal Naked Mole-Rat Ovary: From Primordial Germ Cells to Meiotic Prophase I Oocytes. Methods Mol Biol. 2023;2677:185-201. doi: 10.1007/978-1-0716-3259-8_11. PubMed PMID: 37464243.
- Brieño-Enriquez MA, Duncan FE, Ghazi A, Klutstein M, Sebastiano V, Tyler J. Editorial: Germ cell development and reproductive aging. Front Cell Dev Biol. 2022;10:1051539. doi: 10.3389/fcell.2022.1051539. eCollection 2022. PubMed PMID: 36313559; PubMed Central PMCID: PMC9597615.
- Hense JD, Garcia DN, Isola JV, Alvarado-Rincón JA, Zanini BM, Prosczek JB, Stout MB, Mason JB, Walsh PT, Brieño-Enríquez MA, Schadock I, Barros CC, Masternak MM, Schneider A. Senolytic treatment reverses obesity-mediated senescent cell accumulation in the ovary. Geroscience. 2022 Jun;44(3):1747-1759. doi: 10.1007/s11357-022-00573-9. Epub 2022 Apr 23. PubMed PMID: 35460445; PubMed Central PMCID: PMC9213603.
- Buffenstein R, Amoroso V, Andziak B, Avdieiev S, Azpurua J, Barker AJ, Bennett NC, Brieño-Enríquez MA, Bronner GN, Coen C, Delaney MA, Dengler-Crish CM, Edrey YH, Faulkes CG, Frankel D, Friedlander G, Gibney PA, Gorbunova V, Hine C, Holmes MM, Jarvis JUM, Kawamura Y, Kutsukake N, Kenyon C, Khaled WT, Kikusui T, Kissil J, Lagestee S, Larson J, Lauer A, Lavrenchenko LA, Lee A, Levitt JB, Lewin GR, Lewis Hardell KN, Lin TD, Mason MJ, McCloskey D, McMahon M, Miura K, Mogi K, Narayan V, O'Connor TP, Okanoya K, O'Riain MJ, Park TJ, Place NJ, Podshivalova K, Pamenter ME, Pyott SJ, Reznick J, Ruby JG, Salmon AB, Santos-Sacchi J, Sarko DK, Seluanov A, Shepard A, Smith M, Storey KB, Tian X, Vice EN, Viltard M, Watarai A, Wywial E, Yamakawa M, Zemlemerova ED, Zions M, Smith ESJ. The naked truth: a comprehensive clarification and classification of current 'myths' in naked mole-rat biology. Biol Rev Camb Philos Soc. 2022 Feb;97(1):115-140. doi: 10.1111/brv.12791. Epub 2021 Sep 3. Review. PubMed PMID: 34476892; PubMed Central PMCID: PMC9277573.
- Beverley R, Snook ML, Brieño-Enríquez MA. Meiotic Cohesin and Variants Associated With Human Reproductive Aging and Disease. Front Cell Dev Biol. 2021;9:710033. doi: 10.3389/fcell.2021.710033. eCollection 2021. Review. PubMed PMID: 34409039; PubMed Central PMCID: PMC8365356.
- Place NJ, Prado AM, Faykoo-Martinez M, Brieño-Enriquez MA, Albertini DF, Holmes MM. Germ cell nests in adult ovaries and an unusually large ovarian reserve in the naked mole-rat. Reproduction. 2021 Jan;161(1):89-98. doi: 10.1530/REP-20-0304. PubMed PMID: 33151901; PubMed Central PMCID: PMC7770031.
- Barreñada O, Fernández-Pérez D, Larriba E, Brieño-Enriquez M, Del Mazo J. Diversification of piRNAs expressed in PGCs and somatic cells during embryonic gonadal development. RNA Biol. 2020 Sep;17(9):1309-1323. doi: 10.1080/15476286.2020.1757908. Epub 2020 May 6. PubMed PMID: 32375541; PubMed Central PMCID: PMC7549708.
- Pereira C, Smolka MB, Weiss RS, Brieño-Enríquez MA. ATR signaling in mammalian meiosis: From upstream scaffolds to downstream signaling. Environ Mol Mutagen. 2020 Aug;61(7):752-766. doi: 10.1002/em.22401. Epub 2020 Aug 13. Review. PubMed PMID: 32725817; PubMed Central PMCID: PMC7747128.
- Brieño-Enríquez MA, Moak SL, Abud-Flores A, Cohen PE. Characterization of telomeric repeat-containing RNA (TERRA) localization and protein interactions in primordial germ cells of the mouse†. Biol Reprod. 2019 Apr 1;100(4):950-962. doi: 10.1093/biolre/ioy243. PubMed PMID: 30423030; PubMed Central PMCID: PMC6483056.
- Brieño-Enríquez MA, Moak SL, Holloway JK, Cohen PE. NIMA-related kinase 1 (NEK1) regulates meiosis I spindle assembly by altering the balance between α-Adducin and Myosin X. PLoS One. 2017;12(10):e0185780. doi: 10.1371/journal.pone.0185780. eCollection 2017. PubMed PMID: 28982183; PubMed Central PMCID: PMC5628868.
- Brieño-Enríquez MA, Moak SL, Toledo M, Filter JJ, Gray S, Barbero JL, Cohen PE, Holloway JK. Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the Mouse. Cell Rep. 2016 Oct 18;17(4):977-986. doi: 10.1016/j.celrep.2016.09.059. PubMed PMID: 27760328; PubMed Central PMCID: PMC5123770.
- Brieño-Enríquez MA, Cohen PE. Double trouble in human aneuploidy. Nat Genet. 2015 Jul;47(7):696-8. doi: 10.1038/ng.3344. PubMed PMID: 26111508.
- Brieño-Enríquez MA, García-López J, Cárdenas DB, Guibert S, Cleroux E, Děd L, Hourcade Jde D, Pěknicová J, Weber M, Del Mazo J. Exposure to endocrine disruptor induces transgenerational epigenetic deregulation of microRNAs in primordial germ cells. PLoS One. 2015;10(4):e0124296. doi: 10.1371/journal.pone.0124296. eCollection 2015. PubMed PMID: 25897752; PubMed Central PMCID: PMC4405367.
- Brieño-Enríquez MA, Reig-Viader R, Cabero L, Toran N, Martínez F, Roig I, Garcia Caldés M. Gene expression is altered after bisphenol A exposure in human fetal oocytes in vitro. Mol Hum Reprod. 2012 Apr;18(4):171-83. doi: 10.1093/molehr/gar074. Epub 2011 Nov 25. PubMed PMID: 22121209.
- Brieño-Enríquez MA, Robles P, Camats-Tarruella N, García-Cruz R, Roig I, Cabero L, Martínez F, Caldés MG. Human meiotic progression and recombination are affected by Bisphenol A exposure during in vitro human oocyte development. Hum Reprod. 2011 Oct;26(10):2807-18. doi: 10.1093/humrep/der249. Epub 2011 Jul 26. PubMed PMID: 21795248.
- Brieño-Enríquez MA, Robles P, García-Cruz R, Roig I, Cabero L, Martínez F, Garcia Caldés M. A new culture technique that allows in vitro meiotic prophase development of fetal human oocytes. Hum Reprod. 2010 Jan;25(1):74-84. doi: 10.1093/humrep/dep351. Epub 2009 Oct 14. PubMed PMID: 19828555.
For additional publications, visit Pubmed.
Research Group
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