Echinacoside Increases Sperm Quantity in Rats by Targeting the Hypothalamic Androgen Receptor

Male infertility is a major health issue with an estimated prevalence of 4.2% of male infertility worldwide. Our early work demonstrated that Cistanche extracts protect against sperm damage in mice and that echinacoside (ECH) is one of the major active components. Here we report an essential role fo...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2018-03, Vol.8 (1), p.3839-11, Article 3839
Main Authors: Jiang, Zhihui, Zhou, Bo, Li, Xinping, Kirby, Gordon M., Zhang, Xiaoying
Format: Article
Language:English
Subjects:
38/77
631/154/436
692/163
82/16
82/51
Androgen receptors
Androgens
Cytoplasm
Enzyme-linked immunosorbent assay
Feedback
High-performance liquid chromatography
Humanities and Social Sciences
Hypothalamus
Infertility
Liquid chromatography
Luteinizing hormone
multidisciplinary
Nuclei
Science
Science (multidisciplinary)
Secretion
Sperm
Testosterone
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Male infertility is a major health issue with an estimated prevalence of 4.2% of male infertility worldwide. Our early work demonstrated that Cistanche extracts protect against sperm damage in mice and that echinacoside (ECH) is one of the major active components. Here we report an essential role for ECH, a natural product that reverses or protects against oligoasthenospermia in rats. ECH was assayed by HPLC, the quantity and quality of sperm was evaluated and hormone levels were determined by radioimmunosorbent assay. ECH reduced levels of androgen receptor (AR) and key steroidogenic-related genes as determined by Western blot and qPCR analysis. The interaction between ECH and AR were evaluated by indirect ELISA and molecular docking. The results show that ECH combined with hypothalamic AR in the pocket of Met-894 and Val-713 to inhibit transfer of AR from the cytoplasm to nuclei in the hypothalamus. While negative feedback of sex hormone regulation was inhibited, positive feedback was stimulated to increase the secretion of luteinizing hormone and testosterone subsequently enhancing the quantity of sperm. Taken together, these data demonstrate that ECH blocks AR activity in the hypothalamus to increase the quantity of sperm and protect against oligoasthenospermia in rats.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-22211-1