PARP1 during embryo implantation and its upregulation by oestradiol in mice

Abstract

Pregnancy requires successful implantation of an embryo, which occurs during a restricted period defined as 'receptivity of the endometrium' and is influenced by the ovarian steroids progesterone and oestradiol. The role of poly(ADP-ribose)polymerase-1 (PARP1) in apoptosis is well established. However, it is also involved in cell differentiation, proliferation and tissue remodelling. Previous studies have described the presence of PARP in the uterus, but its exact role in embryo implantation is not yet elucidated. Hence, in this study, we studied the expression of PARP1 in the uterus during embryo implantation and decidualisation, and its regulation by ovarian steroids. Our results show upregulation of the native form of PARP1 (w116 kDa) in the cytosolic and nuclear compartments of implantation and non-implantation sites at day 5 (0500 h), followed by downregulation at day 5 (1000 h), during the embryo implantation period. The transcript level of Parp1 was also augmented during day 5 (0500 h). Inhibition of PARP1 activity by the drug EB-47 decreased the number of embryo implantation sites and blastocysts at day 5 (1000 h). Further, cleavage of native PARP1 was due to the activity of caspase-3 during the peri-implantation stage (day 5 (0500 h)), and is also required for embryo implantation, as inhibition of its activity compromised blastocyst implantation. The native (w116 kDa) and cleaved (w89 kDa) forms of PARP1 were both elevated during decidualisation of the uterus. Furthermore, the expression level of PARP1 in the uterus was found to be under the control of the hormone oestrogen. Our results clearly demonstrate that PARP1 participates in the process of embryo implantation.

Microvesicles provide a mechanism for intercellular communication by embryonic stem cells during embryo implantation

“…5 ). Thus far, the vast majority of the studies examining the mechanisms that underlie implantation have focused on the communication events that occur between maternal cells and trophoblast cells 19 20 58 59 60 61 . Therefore, to the best of our knowledge, the findings reported here provide the first demonstrations that the embryo can send signals which directly promote trophoblast migration and influence the implantation process.…”

The role of ADP-ribose metabolism in metabolic regulation, adipose tissue differentiation, and metabolism

“…PARP1 and PARP2 activation were shown to be a key step in the development of insulin resistance (for review, see Bai and Cantó 2012). Hormones, such as insulin (Horvath et al 2008), estrogens (Mabley et al 2005;Jog and Caricchio 2013;Joshi et al 2014), androgens (Shimizu et al 2013), progesterone (Ghabreau et al 2004), artificial steroids, and vitamin D (Marton et al 2018b) can modulate the expression and activity of PARP1 and PARP2. Endocrine disruptors were also shown to modulate PARP activity (Chen et al 2013;Guerriero et al 2018).…”

Two cases of Oto palate digital syndrome type II: Clinical features and a study of telomere length maintenance pathways.

“…Moreover, PARP-1 has also been reported to be involved in transcriptional regulation of SMAD3 [30], sex determining region Y-Box-2 [31] and E-cadherin [32], most of which are important factors for implantation of embryo. Joshi et al 2014 [33] demonstrated the role of PARP-1 in embryo implantation by preparing the uterus for it. Thus role of PARP-1 in embryonic development in our study cannot be ignored.…”