Follicle-intrinsic and spatially distinct molecular programs drive follicle rupture and luteinization during ex vivo mammalian ovulation.

Autor: Zaniker EJ; Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA., Zhang J; Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA., Russo D; Institute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; Broad Institute, Harvard University & Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; The Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA., Huang R; Thayer School of Engineering, Dartmouth College, Hanover, NH, USA., Suritis K; Thayer School of Engineering, Dartmouth College, Hanover, NH, USA., Drake RS; Institute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; Broad Institute, Harvard University & Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; The Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA., Barlow-Smith E; Micrographia Bio, London, UK., Shalek AK; Institute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; Broad Institute, Harvard University & Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.; The Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA., Woodruff TK; Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.; Department of Obstetrics and Gynecology, Michigan State University, East Lansing, MI, USA., Xiao S; Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA., Goods BA; Thayer School of Engineering, Dartmouth College, Hanover, NH, USA. britt.anne.goods@dartmouth.edu., Duncan FE; Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA. f-duncan@northwestern.edu.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Oct 23; Vol. 7 (1), pp. 1374. Date of Electronic Publication: 2024 Oct 23.
DOI: 10.1038/s42003-024-07074-9
Abstrakt: During ovulation, the apical wall of the preovulatory follicle breaks down to facilitate gamete release. In parallel, the residual follicle wall differentiates into a progesterone-producing corpus luteum. Disruption of ovulation, whether through contraceptive intervention or infertility, has implications for women's health. In this study, we harness the power of an ex vivo ovulation model and machine-learning guided microdissection to identify differences between the ruptured and unruptured sides of the follicle wall. We demonstrate that the unruptured side exhibits clear markers of luteinization after ovulation while the ruptured side exhibits cell death signals. RNA-sequencing of individual follicle sides reveals 2099 differentially expressed genes (DEGs) between follicle sides without ovulation induction, and 1673 DEGs 12 h after induction of ovulation. Our model validates molecular patterns consistent with known ovulation biology even though this process occurs in the absence of the ovarian stroma, vasculature, and immune cells. We further identify previously unappreciated pathways including amino acid transport and Jag-Notch signaling on the ruptured side and glycolysis, metal ion processing, and IL-11 signaling on the unruptured side of the follicle. This study yields key insights into follicle-inherent, spatially-defined pathways that underlie follicle rupture, which may further understanding of ovulation physiology and advance women's health.
(© 2024. The Author(s).)
Databáze: MEDLINE
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