Cumulus expansion is impaired with advanced reproductive age due to loss of matrix integrity and reduced hyaluronan.

Autor: Babayev E; Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA., Suebthawinkul C; Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.; Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand., Gokyer D; Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA., Parkes WS; Department of Pharmacology, Toxicology, & Therapeutics, Institute for Reproductive and Developmental Sciences, University of Kansas Medical Center, Kansas City, Kansas, USA., Rivas F; Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA., Pavone ME; Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA., Hall AR; Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA., Pritchard MT; Department of Pharmacology, Toxicology, & Therapeutics, Institute for Reproductive and Developmental Sciences, University of Kansas Medical Center, Kansas City, Kansas, USA., Duncan FE; Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2023 Nov; Vol. 22 (11), pp. e14004. Date of Electronic Publication: 2023 Oct 18.
DOI: 10.1111/acel.14004
Abstrakt: Reproductive aging is associated with ovulatory defects. Age-related ovarian fibrosis partially contributes to this phenotype as short-term treatment with anti-fibrotic compounds improves ovulation in reproductively old mice. However, age-dependent changes that are intrinsic to the follicle may also be relevant. In this study, we used a mouse model to demonstrate that reproductive aging is associated with impaired cumulus expansion which is accompanied by altered morphokinetic behavior of cumulus cells as assessed by time-lapse microscopy. The extracellular matrix integrity of expanded cumulus-oocyte complexes is compromised with advanced age as evidenced by increased penetration of fluorescent nanoparticles in a particle exclusion assay and larger open spaces on scanning electron microscopy. Reduced hyaluronan (HA) levels, decreased expression of genes encoding HA-associated proteins (e.g., Ptx3 and Tnfaip6), and increased expression of inflammatory genes and matrix metalloproteinases underlie this loss of matrix integrity. Importantly, HA levels are decreased with age in follicular fluid of women, indicative of conserved reproductive aging mechanisms. These findings provide novel mechanistic insights into how defects in cumulus expansion contribute to age-related infertility and may serve as a target to extend reproductive longevity.
(© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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