Knockdown of melatonin receptor 1 and induction of follicle-stimulating hormone on the regulation of mouse granulosa cell function

Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved..

Melatonin receptor 1 (MT1) performs a critical role in the regulation of the animal reproductive system, particularly in follicular growth, and has a considerable effect on reproductive performance. However, the role that MT1 plays in regulating hormones associated with reproduction remains unclear. This study was designed to examine the physiological role of constitutive MT1 silencing and follicle stimulating hormone (FSH) treatment in reproduction, making use of mouse granulosa cells (mGCs) as a model. To understand the constitutive role of MT1 in ovarian physiology, the RNAi-Ready pSIREN-RETROQ-ZsGreen Vector mediated recombinant pshRNA was used to silence MT1 gene expression. Furthermore, we observed that the expression of MT1 was successfully inhibited both at the protein and mRNA levels (P<0.001). We demonstrated that RNAi-B-mediated MT1 down-regulation significantly promoted apoptosis (P<0.001), inhibited proliferation, and regulated the cell cycle at the S-phase; conversely, FSH treatment partially aided the apoptotic effect and improved proliferation but showed a significant effect at the S-phase of the cell cycle. Transitory knockdown of MT1 proved essential in the function of mGCs, as it significantly decreased cyclic adenosine monophospahte (cAMP) level and increased cell apoptosis. Following knockdown of MT1, the expression of Bax was significantly up-regulated (P<0.001), but Bcl-2 was slightly down-regulated, both at the transcriptional and at translational levels. Moreover, the silencing of MT1 and its constitutive effect on FSH significantly promoted an increase in estradiol (P<0.001) and slightly decreased the concentration of progesterone. Together, our data indicates that MT1 suppression leads to interference in the normal physiological function of the ovary by enhancing follicular apoptosis, inhibiting proliferation, and influencing hormonal signaling, whereas constitutive FSH treatment counteracted the negative down-regulatory effects of MT1 on mGCs.

Medienart:

E-Artikel

Erscheinungsjahr:

2017

Erschienen:

2017

Enthalten in:

Zur Gesamtaufnahme - volume:17

Enthalten in:

Reproductive biology - 17(2017), 4 vom: 15. Dez., Seite 380-388

Sprache:

Englisch

Beteiligte Personen:

Talpur, Hira Sajjad [VerfasserIn]
Worku, Tesfaye [VerfasserIn]
Rehman, Zia Ur [VerfasserIn]
Dad, Rahim [VerfasserIn]
Bhattarai, Dinesh [VerfasserIn]
Bano, Iqra [VerfasserIn]
Farmanullah [VerfasserIn]
Liang, Aixin [VerfasserIn]
He, Changjiu [VerfasserIn]
Yang, Liguo [VerfasserIn]

Links:

Volltext

Themen:

4G7DS2Q64Y
4TI98Z838E
9002-68-0
Apoptosis
Bcl-2-Associated X Protein
Cyclic AMP
E0399OZS9N
Estradiol
Follicle Stimulating Hormone
Follicle stimulating hormone
Granulosa cells
Journal Article
Knockdown
Melatonin receptors
Progesterone
Receptor, Melatonin, MT1

Anmerkungen:

Date Completed 27.07.2018

Date Revised 27.07.2018

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.repbio.2017.10.005

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM277643260