PTPN11 (SHP2) Is Indispensable for Growth Factors and Cytokine Signal Transduction During Bovine Oocyte Maturation and Blastocyst Development.

Muhammad Idrees,Il-Keun Kong,Kyeong-Lim Lee,Marwa El Sheikh,Seok-Hwan Song,Lianguang Xu,Tabinda Sidrat,Myeong-Don Joo,Tahir Muhammad

doi:10.3390/cells8101272

Muhammad Idrees, Il-Keun Kong + Show 7 more

Open Access

https://doi.org/10.3390/cells8101272

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Journal: Cells	Publication Date: Oct 18, 2019
Citations: 19	License type: CC BY 4.0

Affiliation: Gyeongsang National University

Abstract

This study was aimed to investigate the role of SHP2 (Src-homology-2-containing phosphotyrosine phosphatase) in intricate signaling networks invoked by bovine oocyte to achieve maturation and blastocyst development. PTPN11 (Protein Tyrosine Phosphatase, non-receptor type 11) encoding protein SHP2, a positive transducer of RTKs (Receptor Tyrosine Kinases) and cytokine receptors, can play a significant role in bovine oocyte maturation and embryo development, but this phenomenon has not yet been explored. Here, we used different growth factors, cytokines, selective activator, and a specific inhibitor of SHP2 to ascertain its role in bovine oocyte developmental stages in vitro. We found that SHP2 became activated by growth factors and cytokines treatment and was highly involved in the activation of oocyte maturation and embryo development pathways. Activation of SHP2 triggered MAPK (mitogen-activated protein kinases) and PI3K/AKT (Phosphoinositide 3-kinase/Protein kinase B) signaling cascades, which is not only important for GVBD (germinal vesical breakdown) induction but also for maternal mRNA translation. Inhibition of phosphatase activity of SHP2 with PHPS1 (Phenylhydrazonopyrazolone sulfonate 1) reduced oocytes maturation as well as bovine blastocyst ICM (inner cell mass) volume. Supplementation of LIF (Leukemia Inhibitory Factor) to embryos showed an unconventional direct relation between p-SHP2 and p-STAT3 (Signal transducer and activator of transcription 3) for blastocyst ICM development. Other than growth factors and cytokines, cisplatin was used to activate SHP2. Cisplatin activated SHP2 modulate growth factors effect and combine treatment significantly enhanced quality and rate of developed blastocysts.

Highlights

An oocyte is a hub containing all of the information necessary for the successful nuclear and cytoplasmic maturation [1]
As a first step toward understanding the role of SHP2, we qualitatively assessed the mRNA expression of PTPN11 in bovine day-8 blastocysts (Figure 1A)
To define the cellular events in which SHP2 is involved during meiotic maturation and embryo development, we examined the distribution of SHP2 at different developmental stages through qRT-PCR and immunofluorescence (Figure 1C,D)

Summary

Introduction

An oocyte is a hub containing all of the information necessary for the successful nuclear and cytoplasmic maturation [1]. The process of maturation is initiated by triggering intricate signaling networks invoked by the oocyte to get competency for fertilization and blastocyst development. Cells 2019, 8, 1272 medium due to their enormous effects on the oocyte in vitro maturation and embryo development [4,5]. Supplementation of these factors activate MAPK 3/1 signaling for oocyte maturation, and PI3K/p-AKT pathway for embryo development [5,6,7]. It was demonstrated that EGF-like growth factors an activator of EGF receptor regulate maternal mRNA translation through MAP kinases and reinforced fertilized zygotes to attain developmental competency by activating the

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