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Exogenous estrogen partially rescues progesterone deficiency and autophagosome enlargement in mcoln1-/-mouse model with lysosomal storage disorder

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生殖与发育医学(英文) 2024年第4期

作者： Wang Zidao Li Yuehuan Andersen Christian L. El Zowalaty Ahmed E. Hancock Jonathan M. Martin Taylor E. Howerth Elizabeth W. Viswanathan Suvitha Byun Haeyeun Ye Xiaoqin Department of Physiology and Pharmacology College of Veterinary Medicine University of Georgia Athens GA USA Interdisciplinary Toxicology Program University of Georgia Athens GA USA Zidao Wang is currently at the Department of Obstetrics Gynecology and Women’s Health University of Missouri Columbia MO USA Yuehuan Li is currently at Beijing Institute of Collaborative Innovation Beijing China Christian L. Andersen is currently at Schr?dinger Broadwayth Floor New York NY USA Ahmed E. El Zowalaty is currently at the Department of Pharmacology and Toxicology Faculty of Pharmacy Zagazig University Zagazig Egypt Department of Pathology College of Veterinary Medicine University of Georgia Athens GA USA

Objective: Femalemcoln1-/- mice exhibit progressive progesterone (P4) deficiency, luteal cell degeneration, and premature embryo implantation failure at 5 months old. We attempted to rescue embryo implantation in non-virginmcoln1-/- mice (5-6 months old) with exogenous P4 treatment on days 1.5 post-coitum (D1.5), D2.5, and D3.5, and observed partially restored luteal cell morphology on D4.5, but unexpectedly found 17β-estradiol (E2) contamination in the P4 working solution. In this study, we aim to investigate exogenous P4 and/or E2 for the partial recovery of luteal cell morphology in infertilemcoln1-/- ***: Control and non-virginmcoln1-/- mice (5-6 months old) were treated with newly ordered vehicle, P4, E2, or P4 + E2 on D1.5 and D2.5 and dissected on D3.5 for P4 and E2 measurements, ovary histology, immunofluorescence, lipid droplet staining, and transmission electron ***: E2 treatment significantly increased serum P4 levels in D3.5mcoln1-/- mice. E2 and P4 + E2 treatments, but not P4 treatment alone, largely improved the morphology of D3.5mcoln1-/- corpora lutea, indicated by a more contiguous web-like collagen IV expression pattern, increased heat shock protein 60 expression, and reduced accumulation of large lipid droplets. Transmission electron microscopy revealed extremely enlarged autophagosomes and lipid droplets, lysosomes with lamellar structures, and mitochondria with reduced cristae in vehicle-treated D3.5mcoln1-/- luteal cells, while in E2-treated D3.5mcoln1-/- luteal cells, extremely enlarged autophagosomes and lipid droplets were reduced, indicating improved luteal cell ***: These findings reveal protective effects of high levels of exogenous E2 on P4 production and lysosomal function inmcoln1-/- luteal cells.

关键词： trpml1/mcoln1 Corpus luteum Progesterone Estrogen Heat shock protein 60 Collagen IV Transmission electron microscopy Autophagosome Lipid droplet

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