scholarly journals Human Endometrial Stromal Cells Are Highly Permissive To Productive Infection by Zika Virus

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Isabel Pagani ◽  
Silvia Ghezzi ◽  
Adele Ulisse ◽  
Alicia Rubio ◽  
Filippo Turrini ◽  
...  
2016 ◽  
Author(s):  
Isabel Pagani ◽  
Silvia Ghezzi ◽  
Adele Ulisse ◽  
Alicia Rubio ◽  
Filippo Turrini ◽  
...  

ABSTRACTZika virus (ZIKV) is a recently re-emerged flavivirus transmitted to humans by mosquito bites but also from mother to fetus and by sexual intercourse. We here show for the first time that primary human endometrial stromal cells (HESC) are highly permissive to ZIKV infection and support its in vitro replication. ZIKV envelope expression was detected in the endoplasmic reticulum whereas double-stranded viral RNA colocalized with vimentin filaments to the perinuclear region. ZIKV productive infection also occurred in the human T-HESC cell line with the induction of interferon-β (IFN-β) and of IFN-stimulated genes. Notably, in vitro decidualization of T-HESC with cyclic AMP and progesterone upregulated the cell surface expression of the ZIKV entry co-receptor AXL and boosted ZIKV replication by ca. 100-fold. Thus, endometrial stromal cells, particularly if decidualized, likely represent a crucial cell target of sexual virus transmission and a relevant source of ZIKV spreading to placental trophoblasts during pregnancy.AUTHOR SUMMARYInfection by Zika virus (ZIKV), a flavivirus transmitted to humans by mosquito bites, has recently emerged as an important cause of neurological lesions in the fetal brain as women who become infected by ZIKV during pregnancy can transmit the virus to their fetus. In addition, routes of ZIKV transmission independent of mosquito bites have been also identified and include sexual transmission from both infected men and women to their partners, an aspect bearing great societal implications for ZIKV spread. These observations highlight the importance of the female reproductive tract in the establishment and/or spreading of the infection. In this regard, the endometrium is a highly dynamic tissue undergoing major histological changes during the menstrual cycle under the coordinated action of sexual hormones. In particular, progesterone drives the differentiation of human endometrial stromal cells towards decidualization, a process that is critical for fetal trophoblast invasion and placenta formation. We here report for the first time that both primary and immortalized human endometrial stromal cells are highly permissive to ZIKV infection and replication, particularly when in vitro decidualized by progesterone, suggesting that these cells could significantly contribute to vertical ZIKV transmission in utero during pregnancy but also to horizontal transmission by the sexual route.


Virology ◽  
1994 ◽  
Vol 202 (1) ◽  
pp. 247-257 ◽  
Author(s):  
Timothy F. Kowalik ◽  
Andrew D. Yurochko ◽  
Clifford A. Rinehart ◽  
Chi-Yu Gregory Lee ◽  
Eng-Shang Huang

2015 ◽  
Vol 75 (07) ◽  
Author(s):  
J Thomczik ◽  
I Beyer ◽  
DM Baston-Büst ◽  
SJ Böddeker ◽  
G Wennemuth ◽  
...  

2006 ◽  
Vol 114 (S 1) ◽  
Author(s):  
S Krenzer ◽  
H Fluhr ◽  
M Deperschmidt ◽  
M Zwirner ◽  
D Wallwiener ◽  
...  

1960 ◽  
Vol XXXIII (II) ◽  
pp. 261-276 ◽  
Author(s):  
G. Hellweg ◽  
J. Ferin ◽  
K. G. Ober

ABSTRACT 65 endometrial biopsies from castrated women who had received either natural or artificial sex hormone therapy were studied microscopically. Attention was paid to various histologic criteria, especially to the number of endometrial granulocytes (»K« cells, KZ). The following was obtained: The »K« cells are completely absent when no hormone substitution therapy is given. They were also lacking when the castrated patients were treated only with oestrogens, even if the dose given was ten-times that found in women during the reproductive ages. In contrast, the »K« cells developed from the endometrial stromal cells only under influence of progesterone, usually appearing first 8–10 days after the administration of the gestagen. The »K« cells were demonstrable in the number corresponding to a normal secretory phase only then, when the oestrogen-progesterone dosage ratio had induced a fully-developed secretory change, as measured by the usual histologic criteria. With an overdosage of oestrogen the »K« cells were either absent or were very sparse. Contrarily, an overdosage of progesterone had no influence on their number. The development of endometrial glands does not always entirely parallel that of the stroma in castrated patients following hormone therapy. A more exact indicator for the proper dose for the production of a secretory phase by hormone therapy seems to be the number of »K« cells in the endometrial stroma.


Reproduction ◽  
2018 ◽  
Author(s):  
Qianrong Qi ◽  
Yifan Yang ◽  
Kailin Wu ◽  
Qingzhen Xie

Recent studies revealed that TMEM16A is involved in several reproductive processes, including ovarian estrogen secretion and ovulation, sperm motility and acrosome reaction, fertilization, and myometrium contraction. However, little is known about the expression and function of TMEM16A in embryo implantation and decidualization. In this study, we focused on the expression and regulation of TMEM16A in mouse uterus during early pregnancy. We found that TMEM16A is up-regulated in uterine endometrium in response to embryo implantation and decidualization. Progesterone treatment could induce TMEM16A expression in endometrial stromal cells through progesterone receptor/c-Myc pathway, which is blocked by progesterone receptor antagonist or the inhibitor of c-Myc signaling pathway. Inhibition of TMEM16A by small molecule inhibitor (T16Ainh-A01) resulted in impaired embryo implantation and decidualization in mice. Treatment with either specific siRNA of Tmem16a or T16Ainh-A01 inhibited the decidualization and proliferation of mouse endometrial stromal cells. In conclusion, our results revealed that TMEM16A is involved in embryo implantation and decidualization in mice, compromised function of TMEM16A may lead to impaired embryo implantation and decidualization.


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