Phosphoinositide 3-Kinase (PI3K) Subunit p110δ Is Essential for Trophoblast Cell Differentiation and Placental Development in Mouse
Authors: Yuxiang Ye
Jiangchao Li
Xuesong Yang
Quliang Gu
Qianqian Zhang
Xiaohan Zhang
Jingli Zhang
Sun-Wei Guo
Lingyun Zheng
Lijing Wang
Guang Wang
Xiwen Hu
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: Maternal PI3K p110δ; litter sizes; mice; placenta; embryonic development
Affiliations: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou 510006, China., School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou, 510006, Guangdong, China., Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology &Embryology, Medical College, Jinan University, Guangzhou 510632, China., Shanghai OB/GYN Hospital, Fudan University, Shanghai 200011, China., Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China.

Abstract:  Maternal PI3K p110δ has been implicated in smaller litter sizes in mice, but its underlying mechanism remains unclear. The placenta is an indispensable chimeric organ that supports mammalian embryonic development. Using a mouse model of genetic inactivation of PI3K p110δ (p110δ(D910A/D910A)), we show that fetuses carried by p110δ(D910A/D910A) females were growth retarded and showed increased mortality in utero mainly during placentation. The placentas in p110δ(D910A/D910A) females were anomalously anemic, exhibited thinner spongiotrophoblast layer and looser labyrinth zone, which indicate defective placental vasculogenesis. In addition, p110δ was detected in primary trophoblast giant cells (P-TGC) at early placentation. Maternal PI3K p110δ inactivation affected normal TGCs generation and expansion, impeded the branching of chorioallantoic placenta but enhanced the expression of matrix metalloproteinases (MMP-2, MMP-12). Poor vasculature support for the developing fetoplacental unit resulted in fetal death or gross growth retardation. These data, taken together, provide the first in vivo evidence that p110δ may play an important role in placental vascularization through manipulating trophoblast giant cell. 

Retracted: No

PubPeer comments:
 Could the authors examine Figure 5M to ensure that these images represent the original data? When viewed in inverse, unusual markings appear in the Mash2 bands, including a possible splice between the right-hand Mash2 bands. *** Inverse ![file] *** Original ![file] , 
 Hi, as shown in the figures, the Mash2 bands are not being touched. The marks just remove the stains on the periphery of band. We confirmed that the image represents the original data. The following figures are original data. ![file] , 
 #2 Thank you for your reply. The image you provided appears to match only one of the bands (blue arrow) I expressed concerns about. The other (red box) has visible edits and a possible splice as illustrated in #1. *** ![file] , 
 I attached the whole process. Thank you for pointing it out. We appreciated that.![file] , 
 20 April 2020  This Article contains an error in Figure 5u2009M, as an incorrect image was used for Mash2 E15.5. The correct Figure 5u2009M appears below as Fig. 1. ![file] The original uncropped gel image for Mash2 E15.5 appears below as Fig. 2. ![file] The conclusions of the Article are unaffected by these changes. ,