Microcystin-leucine arginine inhibits gonadotropin-releasing hormone synthesis in mice hypothalamus

Jing Wang, Yabing Chen, Zhangpeng Chen, Zou Xiang, Jie Ding, Xiaodong Han

Research output: Journal article publicationJournal articleAcademic researchpeer-review

5 Citations (Scopus)

Abstract

Microcystin-leucine arginine (MC-LR) causes serum testosterone declines and male reproductive disorders. However, the molecular mechanisms underlying the pathological changes are still unclear. In the present study, we aimed to investigate the toxic effects of MC-LR on gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus. Our results demonstrated that MC-LR could enter GnRH neurons and inhibit GnRH synthesis, resulting in the decrease of serum GnRH and testosterone levels. The inhibitory effects of MC-LR on GnRH synthesis were identified to be associated with activation of the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP response element-binding protein (CREB)/c-Fos signaling pathway. With miRNA microarray analyses, we found that miR-329-3p was down-regulated most dramatically in MC-LR-treated GT1–7 cells. We then further identified that miR-329-3p regulated PRKAR1A and PRKACB expression and thus influenced GnRH synthesis. This is the first study to explore the molecular mechanism underlying the inhibitory effects of MC-LR on GnRH synthesis in the hypothalamus. Our data have provided a new perspective in the development of diagnosis and treatment strategies for male infertility as a result of dysfunction of the hypothalamic-pituitary-gonadal axis.

Original languageEnglish
Pages (from-to)391-399
Number of pages9
JournalEcotoxicology and Environmental Safety
Volume163
DOIs
Publication statusPublished - 15 Nov 2018

Keywords

  • Gonadotropin-releasing hormone
  • Hypothalamic-pituitary-gonadal axis
  • Microcystin-leucine argine
  • Water contamination

ASJC Scopus subject areas

  • Pollution
  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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