A Dose-Response Study on Functional and Transcriptomic Effects of FSH on Ex Vivo Mouse Folliculogenesis.

Autor:	Zhan T; Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.; Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ 08854, USA.; Center for Environmental Exposures and Disease, Rutgers University, Piscataway, NJ 08854, USA., Zhang J; Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.; Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ 08854, USA.; Center for Environmental Exposures and Disease, Rutgers University, Piscataway, NJ 08854, USA., Zhang Y; Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.; Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ 08854, USA.; Center for Environmental Exposures and Disease, Rutgers University, Piscataway, NJ 08854, USA., Zhao Q; Department of Obstetrics, Gynecology and Reproductive Health, New Jersey Medical School (NJMS), Rutgers University, Newark, NJ 07103, USA., Chemerinski A; Department of Obstetrics, Gynecology and Reproductive Health, New Jersey Medical School (NJMS), Rutgers University, Newark, NJ 07103, USA., Douglas NC; Department of Obstetrics, Gynecology and Reproductive Health, New Jersey Medical School (NJMS), Rutgers University, Newark, NJ 07103, USA.; Center for Immunity and Inflammation, Rutgers Biomedical and Health Sciences (RBHS), Newark, NJ 07103, USA., Zhang Q; Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA., Xiao S; Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.; Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ 08854, USA.; Center for Environmental Exposures and Disease, Rutgers University, Piscataway, NJ 08854, USA.
Jazyk:	angličtina
Zdroj:	Endocrinology [Endocrinology] 2024 May 27; Vol. 165 (7).
DOI:	10.1210/endocr/bqae054
Abstrakt:	Follicle-stimulating hormone (FSH) binds to its membrane receptor (FSHR) in granulosa cells to activate various signal transduction pathways and drive the gonadotropin-dependent phase of folliculogenesis. Both FSH insufficiency (due to genetic or nongenetic factors) and FSH excess (as encountered with ovarian stimulation in assisted reproductive technology [ART]) can cause poor female reproductive outcomes, but the underlying molecular mechanisms remain elusive. Herein, we conducted single-follicle and single-oocyte RNA sequencing analysis along with other approaches in an ex vivo mouse folliculogenesis and oogenesis system to investigate the effects of different concentrations of FSH on key follicular events. Our study revealed that a minimum FSH threshold is required for follicle maturation into the high estradiol-secreting preovulatory stage, and such threshold is moderately variable among individual follicles between 5 and 10 mIU/mL. FSH at 5, 10, 20, and 30 mIU/mL induced distinct expression patterns of follicle maturation-related genes, follicular transcriptomics, and follicular cAMP levels. RNA sequencing analysis identified FSH-stimulated activation of G proteins and downstream canonical and novel signaling pathways that may critically regulate follicle maturation, including the cAMP/PKA/CREB, PI3K/AKT/FOXO1, and glycolysis pathways. High FSH at 20 and 30 mIU/mL resulted in noncanonical FSH responses, including premature luteinization, high production of androgen and proinflammatory factors, and reduced expression of energy metabolism-related genes in oocytes. Together, this study improves our understanding of gonadotropin-dependent folliculogenesis and provides crucial insights into how high doses of FSH used in ART may impact follicular health, oocyte quality, pregnancy outcome, and systemic health. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)
Databáze:	MEDLINE
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