title: A uterine decidual cell cytokine ensures pregnancy-dependent adaptations to a physiological stressor.
abstract: In the mouse, decidual cells differentiate from uterine stromal cells in response to steroid hormones and signals arising from the embryo. Decidual cells are crucially involved in creating the intrauterine environment conducive to embryonic development. Among their many functions is the production of cytokines related to prolactin (PRL), including decidual prolactin-related protein (DPRP). DPRP is a heparin-binding cytokine, which is abundantly expressed in uterine decidua. In this investigation, we have isolated the mouse Dprp gene, characterized its structure and evaluated its biological role. Dprp-null mice were made by replacing exons 2 to 6 of the Dprp gene with an in-frame enhanced green fluorescent protein (EGFP) gene and a neomycin (neo) resistance cassette. Heterozygous intercross breeding of the mutant mice yielded the expected mendelian ratio. Pregnant heterozygote females expressed EGFP within decidual tissue in locations identical to endogenous Dprp mRNA and protein expression. Homozygous Dprp-null mutant male and female mice were viable, exhibited normal postnatal growth rates, were fertile and produced normal litter sizes. A prominent phenotype was observed when pregnant Dprp-null mice were exposed to a physiological stressor. DPRP deficiency interfered with pregnancy-dependent adaptations to hypoxia resulting in pregnancy failure. Termination of pregnancy was associated with aberrations in mesometrial decidual cells, mesometrial vascular integrity, and disruptions in chorioallantoic placenta morphogenesis. The observations suggest that DPRP participates in pregnancy-dependent adaptations to a physiological stressor.
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute of Maternal-Fetal Biology, Division of Cancer and Developmental Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: S M Khorshed
authors.initials: SM
authors.lastname: Alam
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Konno
authors.forename: Gouli
authors.initials: G
authors.lastname: Dai
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Danhua
authors.initials: D
authors.lastname: Wang
authors.forename: Judy H
authors.initials: JH
authors.lastname: Dunmore
authors.forename: Alan R
authors.initials: AR
authors.lastname: Godwin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Soares
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D016207:Cytokines / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D003656:Decidua / Q000166:cytology / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics; D000860:Hypoxia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D011247:Pregnancy; D011388:Prolactin / Q000031:analogs & derivatives* / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics
chemical_list: D016207:Cytokines; D017931:DNA Primers; C489796:Dtprp protein, mouse; D012333:RNA, Messenger; D011994:Recombinant Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D011388:Prolactin