title: 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 (∼116 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 (∼116 kDa) and cleaved (∼89 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.
authors: Division of EndocrinologyLife Science North 111B/101Division of PharmacologyPreclinical South 201, CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors: Anubha
authors: A
authors: Joshi
authors: Division of EndocrinologyLife Science North 111B/101Division of PharmacologyPreclinical South 201, CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors: Sahil
authors: S
authors: Mahfooz
authors: Division of EndocrinologyLife Science North 111B/101Division of PharmacologyPreclinical South 201, CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors: Vineet Kumar
authors: VK
authors: Maurya
authors: Division of EndocrinologyLife Science North 111B/101Division of PharmacologyPreclinical South 201, CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors: Vijay
authors: V
authors: Kumar
authors: Division of EndocrinologyLife Science North 111B/101Division of PharmacologyPreclinical South 201, CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors: Chadchan Sangappa
authors: CS
authors: Basanna
authors: Division of EndocrinologyLife Science North 111B/101Division of PharmacologyPreclinical South 201, CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors: Gurpreet
authors: G
authors: Kaur
authors: Division of EndocrinologyLife Science North 111B/101Division of PharmacologyPreclinical South 201, CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors: Kashif
authors: K
authors: Hanif
authors: Division of EndocrinologyLife Science North 111B/101Division of PharmacologyPreclinical South 201, CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India rajesh_jha@cdri.res.in.
authors: Rajesh Kumar
authors: RK
authors: Jha
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D003656:Decidua / Q000187:drug effects / Q000201:enzymology; D010064:Embryo Implantation / Q000187:drug effects*; D010065:Embryo Implantation, Delayed / Q000187:drug effects; D004717:Endometrium / Q000187:drug effects* / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005300:Fertility Agents, Female / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D051379:Mice; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D011555:Pseudopregnancy / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D061945:Caspase Inhibitors; D005300:Fertility Agents, Female; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C505409:Casp3 protein, mouse; D053148:Caspase 3