Effects of chemosynthetic choline plasmalogens on gonadotropin secretion from bovine gonadotrophs

Ethanolamine plasmalogens (EPls) and choline plasmalogens (CPls), unique glycerophospholipids may play important roles in milk production and reproduction in postpartum dairy cows. While CPls are more abundant in bovine blood, EPls are predominant in the brain. Brain EPls are the only recognized lig...

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Main Authors: Hiroya KADOKAWA, Yvan Bienvenu NIYONZIMA, Takatsugu HIROKAWA, Ryunosuke YOSHINO
Format: Article
Language:English
Published: The Society for Reproduction and Development 2025-06-01
Series:The Journal of Reproduction and Development
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Online Access:https://www.jstage.jst.go.jp/article/jrd/71/4/71_2025-019/_pdf/-char/en
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author Hiroya KADOKAWA
Yvan Bienvenu NIYONZIMA
Takatsugu HIROKAWA
Ryunosuke YOSHINO
author_facet Hiroya KADOKAWA
Yvan Bienvenu NIYONZIMA
Takatsugu HIROKAWA
Ryunosuke YOSHINO
author_sort Hiroya KADOKAWA
collection DOAJ
description Ethanolamine plasmalogens (EPls) and choline plasmalogens (CPls), unique glycerophospholipids may play important roles in milk production and reproduction in postpartum dairy cows. While CPls are more abundant in bovine blood, EPls are predominant in the brain. Brain EPls are the only recognized ligands of G protein-coupled receptor 61 (GPR61), a receptor that co-localizes with GnRH receptors on gonadotrophs. We hypothesized that chemosynthetic CPls stimulate gonadotropin secretion from bovine gonadotrophs, similar to the reported effects of chemosynthetic EPls. Anterior pituitary cells from healthy, post-pubertal heifers, were cultured for 3.5 days and then treated with increasing concentrations (0, 0.7, 7, 70, or 700 pM) of EPl with vinyl-ether-bonded stearic acid and ester-bonded oleic acid (C18:0-C18:1EPl) as a positive control, or CPls with vinyl-ether-bonded stearic acid and ester-bonded oleic acid (C18:0-C18:1CPl), arachidonic acid (C18:0-C20:4CPl), or docosahexaenoic acid (C18:0-C22:6CPl). After 2 h, the medium samples were harvested for FSH and LH assays. C18:0-C18:1EPl (7–700 pM) stimulated basal FSH and LH secretion (P < 0.01). None of the tested CPl concentrations stimulated LH secretion. Only 700 pM of C18:0-C18:1CPl, but not lower concentrations, stimulated FSH secretion (P < 0.05), an effect that was inhibited by a SMAD pathway inhibitor. However, both C18:0-C18:1CPl and C18:0-C20:4CPl synergized with GnRH to stimulate FSH secretion. In silico molecular-docking simulations using the deep-learning algorithm ColabFold revealed that CPls bind to the three-dimensional structural model of GPR61. In conclusion, C18:0-C20:4CPl stimulated FSH secretion exclusively in the presence of GnRH, whereas C18:0-C18:1CPl weakly stimulated FSH secretion and showed potential interaction with the GnRH signaling pathways.
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publisher The Society for Reproduction and Development
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spelling doaj-art-9ae89cc71e1446dd8743fce1283943a82025-08-20T02:59:16ZengThe Society for Reproduction and DevelopmentThe Journal of Reproduction and Development0916-88181348-44002025-06-0171420120910.1262/jrd.2025-019jrdEffects of chemosynthetic choline plasmalogens on gonadotropin secretion from bovine gonadotrophsHiroya KADOKAWA0Yvan Bienvenu NIYONZIMA1Takatsugu HIROKAWA2Ryunosuke YOSHINO3Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi 753-8515, JapanFaculty of Veterinary Medicine, Yamaguchi University, Yamaguchi 753-8515, JapanDivision of Biomedical Science, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, JapanDivision of Biomedical Science, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, JapanEthanolamine plasmalogens (EPls) and choline plasmalogens (CPls), unique glycerophospholipids may play important roles in milk production and reproduction in postpartum dairy cows. While CPls are more abundant in bovine blood, EPls are predominant in the brain. Brain EPls are the only recognized ligands of G protein-coupled receptor 61 (GPR61), a receptor that co-localizes with GnRH receptors on gonadotrophs. We hypothesized that chemosynthetic CPls stimulate gonadotropin secretion from bovine gonadotrophs, similar to the reported effects of chemosynthetic EPls. Anterior pituitary cells from healthy, post-pubertal heifers, were cultured for 3.5 days and then treated with increasing concentrations (0, 0.7, 7, 70, or 700 pM) of EPl with vinyl-ether-bonded stearic acid and ester-bonded oleic acid (C18:0-C18:1EPl) as a positive control, or CPls with vinyl-ether-bonded stearic acid and ester-bonded oleic acid (C18:0-C18:1CPl), arachidonic acid (C18:0-C20:4CPl), or docosahexaenoic acid (C18:0-C22:6CPl). After 2 h, the medium samples were harvested for FSH and LH assays. C18:0-C18:1EPl (7–700 pM) stimulated basal FSH and LH secretion (P < 0.01). None of the tested CPl concentrations stimulated LH secretion. Only 700 pM of C18:0-C18:1CPl, but not lower concentrations, stimulated FSH secretion (P < 0.05), an effect that was inhibited by a SMAD pathway inhibitor. However, both C18:0-C18:1CPl and C18:0-C20:4CPl synergized with GnRH to stimulate FSH secretion. In silico molecular-docking simulations using the deep-learning algorithm ColabFold revealed that CPls bind to the three-dimensional structural model of GPR61. In conclusion, C18:0-C20:4CPl stimulated FSH secretion exclusively in the presence of GnRH, whereas C18:0-C18:1CPl weakly stimulated FSH secretion and showed potential interaction with the GnRH signaling pathways.https://www.jstage.jst.go.jp/article/jrd/71/4/71_2025-019/_pdf/-char/encolabfolddrug discoveryfollicle-stimulating hormonegonadotropin-releasing hormone receptorluteinizing hormone
spellingShingle Hiroya KADOKAWA
Yvan Bienvenu NIYONZIMA
Takatsugu HIROKAWA
Ryunosuke YOSHINO
Effects of chemosynthetic choline plasmalogens on gonadotropin secretion from bovine gonadotrophs
The Journal of Reproduction and Development
colabfold
drug discovery
follicle-stimulating hormone
gonadotropin-releasing hormone receptor
luteinizing hormone
title Effects of chemosynthetic choline plasmalogens on gonadotropin secretion from bovine gonadotrophs
title_full Effects of chemosynthetic choline plasmalogens on gonadotropin secretion from bovine gonadotrophs
title_fullStr Effects of chemosynthetic choline plasmalogens on gonadotropin secretion from bovine gonadotrophs
title_full_unstemmed Effects of chemosynthetic choline plasmalogens on gonadotropin secretion from bovine gonadotrophs
title_short Effects of chemosynthetic choline plasmalogens on gonadotropin secretion from bovine gonadotrophs
title_sort effects of chemosynthetic choline plasmalogens on gonadotropin secretion from bovine gonadotrophs
topic colabfold
drug discovery
follicle-stimulating hormone
gonadotropin-releasing hormone receptor
luteinizing hormone
url https://www.jstage.jst.go.jp/article/jrd/71/4/71_2025-019/_pdf/-char/en
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AT takatsuguhirokawa effectsofchemosyntheticcholineplasmalogensongonadotropinsecretionfrombovinegonadotrophs
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