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Neonatal Progesterone Programs Adult Uterine Responses to Progesterone and Susceptibility to Uterine Dysfunction.
- Source :
-
Endocrinology [Endocrinology] 2015 Oct; Vol. 156 (10), pp. 3791-803. Date of Electronic Publication: 2015 Jul 23. - Publication Year :
- 2015
-
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.
- Subjects :
- Age Factors
Animals
Animals, Newborn
Decidua drug effects
Decidua metabolism
Female
Fertility drug effects
Fertility genetics
Gene Expression Regulation, Developmental drug effects
Genetic Predisposition to Disease etiology
Immunohistochemistry
Male
Mutation
Pregnancy
Progesterone blood
Progestins toxicity
Rats, Inbred BN
Rats, Sprague-Dawley
Receptors, Progesterone genetics
Receptors, Progesterone metabolism
Reverse Transcriptase Polymerase Chain Reaction
Sexual Maturation drug effects
Sexual Maturation genetics
Transcriptome drug effects
Uterine Diseases chemically induced
Uterine Diseases physiopathology
Uterus metabolism
Uterus physiopathology
Genetic Predisposition to Disease genetics
Progesterone toxicity
Uterine Diseases genetics
Uterus drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7170
- Volume :
- 156
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 26204463
- Full Text :
- https://doi.org/10.1210/en.2015-1397