title: Neonatal Progesterone Programs Adult Uterine Responses to Progesterone and Susceptibility to Uterine Dysfunction.
abstract: In this report, we investigated the consequences of neonatal progesterone exposure on adult rat uterine function. Female pups were subcutaneously injected with vehicle or progesterone from postnatal days 3 to 9. Early progesterone exposure affected endometrial gland biogenesis, puberty, decidualization, and fertility. Because decidualization and pregnancy success are directly linked to progesterone action on the uterus, we investigated the responsiveness of the adult uterus to progesterone. We first identified progesterone-dependent uterine gene expression using RNA sequencing and quantitative RT-PCR in Holtzman Sprague-Dawley rats and progesterone-resistant Brown Norway rats. The impact of neonatal progesterone treatment on adult uterine progesterone responsiveness was next investigated using quantitative RT-PCR. Progesterone resistance affected the spectrum and total number of progesterone-responsive genes and the magnitude of uterine responses for a subset of progesterone targets. Several progesterone-responsive genes in adult uterus exhibited significantly dampened responses in neonatally progesterone-treated females compared with those of vehicle-treated controls, whereas other progesterone-responsive transcripts did not differ between female rats exposed to vehicle or progesterone as neonates. The organizational actions of progesterone on the uterus were dependent on signaling through the progesterone receptor but not estrogen receptor 1. To summarize, neonatal progesterone exposure leads to disturbances in endometrial gland biogenesis, progesterone resistance, and uterine dysfunction. Neonatal progesterone effectively programs adult uterine responsiveness to progesterone.
authors.affiliation: Institute for Reproductive Health and Regenerative Medicine, Departments of Pathology and Laboratory Medicine (P.D., M.A.K.R., K.K., D.C., M.J.S.), Cancer Biology (J.C.), and Anatomy and Cell Biology (K.F.R.), University of Kansas Medical Center, Kansas City, Kansas 66160.
authors.forename: Pramod
authors.initials: P
authors.lastname: Dhakal
authors.affiliation: Institute for Reproductive Health and Regenerative Medicine, Departments of Pathology and Laboratory Medicine (P.D., M.A.K.R., K.K., D.C., M.J.S.), Cancer Biology (J.C.), and Anatomy and Cell Biology (K.F.R.), University of Kansas Medical Center, Kansas City, Kansas 66160.
authors.forename: M A Karim
authors.initials: MA
authors.lastname: Rumi
authors.affiliation: Institute for Reproductive Health and Regenerative Medicine, Departments of Pathology and Laboratory Medicine (P.D., M.A.K.R., K.K., D.C., M.J.S.), Cancer Biology (J.C.), and Anatomy and Cell Biology (K.F.R.), University of Kansas Medical Center, Kansas City, Kansas 66160.
authors.forename: Kaiyu
authors.initials: K
authors.lastname: Kubota
authors.affiliation: Institute for Reproductive Health and Regenerative Medicine, Departments of Pathology and Laboratory Medicine (P.D., M.A.K.R., K.K., D.C., M.J.S.), Cancer Biology (J.C.), and Anatomy and Cell Biology (K.F.R.), University of Kansas Medical Center, Kansas City, Kansas 66160.
authors.forename: Damayanti
authors.initials: D
authors.lastname: Chakraborty
authors.affiliation: Institute for Reproductive Health and Regenerative Medicine, Departments of Pathology and Laboratory Medicine (P.D., M.A.K.R., K.K., D.C., M.J.S.), Cancer Biology (J.C.), and Anatomy and Cell Biology (K.F.R.), University of Kansas Medical Center, Kansas City, Kansas 66160.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Chien
authors.affiliation: Institute for Reproductive Health and Regenerative Medicine, Departments of Pathology and Laboratory Medicine (P.D., M.A.K.R., K.K., D.C., M.J.S.), Cancer Biology (J.C.), and Anatomy and Cell Biology (K.F.R.), University of Kansas Medical Center, Kansas City, Kansas 66160.
authors.forename: Katherine F
authors.initials: KF
authors.lastname: Roby
authors.affiliation: Institute for Reproductive Health and Regenerative Medicine, Departments of Pathology and Laboratory Medicine (P.D., M.A.K.R., K.K., D.C., M.J.S.), Cancer Biology (J.C.), and Anatomy and Cell Biology (K.F.R.), University of Kansas Medical Center, Kansas City, Kansas 66160.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Soares
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D003656:Decidua / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005298:Fertility / Q000187:drug effects / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D020022:Genetic Predisposition to Disease / Q000209:etiology / Q000235:genetics*; D007150:Immunohistochemistry; D008297:Male; D009154:Mutation; D011247:Pregnancy; D011374:Progesterone / Q000097:blood / Q000633:toxicity*; D011372:Progestins / Q000633:toxicity; D011914:Rats, Inbred BN; D017207:Rats, Sprague-Dawley; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012741:Sexual Maturation / Q000187:drug effects / Q000235:genetics; D059467:Transcriptome / Q000187:drug effects; D014591:Uterine Diseases / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D011372:Progestins; D011980:Receptors, Progesterone; D011374:Progesterone