Patulin Stimulates Progenitor Leydig Cell Proliferation but Delays Its Differentiation in Male Rats during Prepuberty

Patulin is a mycotoxin with potential reproductive toxicity. We explored the impact of patulin on Leydig cell (LC) development in male rats. Male Sprague Dawley rats (21 days postpartum) were gavaged patulin at doses of 0.5, 1, and 2 mg/kg/day for 7 days. Patulin markedly lowered serum testosterone...

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Main Authors: Huitao Li, Ming Su, Hang Lin, Jingjing Li, Shaowei Wang, Lei Ye, Xingwang Li, Renshan Ge
Format: Article
Language:English
Published: MDPI AG 2023-09-01
Series:Toxins
Subjects:
Online Access:https://www.mdpi.com/2072-6651/15/9/581
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author Huitao Li
Ming Su
Hang Lin
Jingjing Li
Shaowei Wang
Lei Ye
Xingwang Li
Renshan Ge
author_facet Huitao Li
Ming Su
Hang Lin
Jingjing Li
Shaowei Wang
Lei Ye
Xingwang Li
Renshan Ge
author_sort Huitao Li
collection DOAJ
description Patulin is a mycotoxin with potential reproductive toxicity. We explored the impact of patulin on Leydig cell (LC) development in male rats. Male Sprague Dawley rats (21 days postpartum) were gavaged patulin at doses of 0.5, 1, and 2 mg/kg/day for 7 days. Patulin markedly lowered serum testosterone at ≥0.5 mg/kg and progesterone at 1 and 2 mg/kg, while increasing LH levels at 2 mg/kg. Patulin increased the CYP11A1<sup>+</sup> (cholesterol side-chain cleavage, a progenitor LC biomarker) cell number and their proliferation at 1 and 2 mg/kg. Additionally, patulin downregulated <i>Lhcgr</i> (luteinizing hormone receptor), <i>Scarb1</i> (high-density lipoprotein receptor), and <i>Cyp17a1</i> (17α-hydroxylase/17,20-lyase) at 1 and 2 mg/kg. It increased the activation of pAKT1 (protein kinase B), pERK1/2 (extracellular signal-related kinases 1 and 2), pCREB (cyclic AMP response binding protein), and CCND1 (cyclin D1), associated with cell cycle regulation, in vivo. Patulin increased EdU incorporation into R2C LC and stimulated cell cycle progression in vitro. Furthermore, patulin showed a direct inhibitory effect on 11β-HSD2 (11β-hydroxysteroid dehydrogenase 2) activity, which eliminates the adverse effects of glucocorticoids. This study provides insights into the potential mechanisms via which patulin affects progenitor LC development in young male rats.
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spelling doaj.art-4f03ab2d0932465b838637c46fbf9c032023-11-19T13:16:21ZengMDPI AGToxins2072-66512023-09-0115958110.3390/toxins15090581Patulin Stimulates Progenitor Leydig Cell Proliferation but Delays Its Differentiation in Male Rats during PrepubertyHuitao Li0Ming Su1Hang Lin2Jingjing Li3Shaowei Wang4Lei Ye5Xingwang Li6Renshan Ge7Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaPatulin is a mycotoxin with potential reproductive toxicity. We explored the impact of patulin on Leydig cell (LC) development in male rats. Male Sprague Dawley rats (21 days postpartum) were gavaged patulin at doses of 0.5, 1, and 2 mg/kg/day for 7 days. Patulin markedly lowered serum testosterone at ≥0.5 mg/kg and progesterone at 1 and 2 mg/kg, while increasing LH levels at 2 mg/kg. Patulin increased the CYP11A1<sup>+</sup> (cholesterol side-chain cleavage, a progenitor LC biomarker) cell number and their proliferation at 1 and 2 mg/kg. Additionally, patulin downregulated <i>Lhcgr</i> (luteinizing hormone receptor), <i>Scarb1</i> (high-density lipoprotein receptor), and <i>Cyp17a1</i> (17α-hydroxylase/17,20-lyase) at 1 and 2 mg/kg. It increased the activation of pAKT1 (protein kinase B), pERK1/2 (extracellular signal-related kinases 1 and 2), pCREB (cyclic AMP response binding protein), and CCND1 (cyclin D1), associated with cell cycle regulation, in vivo. Patulin increased EdU incorporation into R2C LC and stimulated cell cycle progression in vitro. Furthermore, patulin showed a direct inhibitory effect on 11β-HSD2 (11β-hydroxysteroid dehydrogenase 2) activity, which eliminates the adverse effects of glucocorticoids. This study provides insights into the potential mechanisms via which patulin affects progenitor LC development in young male rats.https://www.mdpi.com/2072-6651/15/9/581mycotoxintestosteroneprogesteronecell cyclesteroidogenesis
spellingShingle Huitao Li
Ming Su
Hang Lin
Jingjing Li
Shaowei Wang
Lei Ye
Xingwang Li
Renshan Ge
Patulin Stimulates Progenitor Leydig Cell Proliferation but Delays Its Differentiation in Male Rats during Prepuberty
Toxins
mycotoxin
testosterone
progesterone
cell cycle
steroidogenesis
title Patulin Stimulates Progenitor Leydig Cell Proliferation but Delays Its Differentiation in Male Rats during Prepuberty
title_full Patulin Stimulates Progenitor Leydig Cell Proliferation but Delays Its Differentiation in Male Rats during Prepuberty
title_fullStr Patulin Stimulates Progenitor Leydig Cell Proliferation but Delays Its Differentiation in Male Rats during Prepuberty
title_full_unstemmed Patulin Stimulates Progenitor Leydig Cell Proliferation but Delays Its Differentiation in Male Rats during Prepuberty
title_short Patulin Stimulates Progenitor Leydig Cell Proliferation but Delays Its Differentiation in Male Rats during Prepuberty
title_sort patulin stimulates progenitor leydig cell proliferation but delays its differentiation in male rats during prepuberty
topic mycotoxin
testosterone
progesterone
cell cycle
steroidogenesis
url https://www.mdpi.com/2072-6651/15/9/581
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