Uterine Notch2 facilitates pregnancy recognition and corpus luteum maintenance via upregulating decidual Prl8a2

Autor: Yan-Ling Wang, Lili Du, Haili Bao, Haibin Wang, Ningjie Yang, Zhangli Ni, Shuangbo Kong, Gaizhen Li, Dunjin Chen, Yang Sun, Yedong Tang, Na Deng
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Cancer Research
Pituitary gland
Embryology
Maternal Health
Peptide Hormones
Placenta
QH426-470
Nervous System
Biochemistry
Mice
Cell Signaling
Pregnancy
Medicine and Health Sciences
Receptor
Notch2
Genetics (clinical)
Progesterone
Notch Signaling
Decidua
Obstetrics and Gynecology
Animal Models
Ovaries
medicine.anatomical_structure
Experimental Organism Systems
Pituitary Gland
Knockout mouse
Corpus Luteum Maintenance
Female
Anatomy
Corpus luteum
hormones
hormone substitutes
and hormone antagonists
Research Article
Signal Transduction
endocrine system
Notch signaling pathway
Endocrine System
Mouse Models
Biology
Research and Analysis Methods
Andrology
Model Organisms
Corpus Luteum
medicine
Genetics
Animals
Embryo Implantation
Molecular Biology
Ecology
Evolution
Behavior and Systematics
RBPJ
Uterus
Embryos
Reproductive System
Biology and Life Sciences
Cell Biology
Prolactin
Hormones
Neuroanatomy
Animal Studies
Women's Health
Neuroscience
Developmental Biology
Zdroj: PLoS Genetics, Vol 17, Iss 8, p e1009786 (2021)
PLoS Genetics
ISSN: 1553-7404
1553-7390
Popis: The maternal recognition of pregnancy is a necessary prerequisite for gestation maintenance through prolonging the corpus luteum lifespan and ensuring progesterone production. In addition to pituitary prolactin and placental lactogens, decidual derived prolactin family members have been presumed to possess luteotropic effect. However, there was a lack of convincing evidence to support this hypothesis. Here, we unveiled an essential role of uterine Notch2 in pregnancy recognition and corpus luteum maintenance. Uterine-specific deletion of Notch2 did not affect female fertility. Nevertheless, the expression of decidual Prl8a2, a member of the prolactin family, was downregulated due to Notch2 ablation. Subsequently, we interrupted pituitary prolactin function to determine the luteotropic role of the decidua by employing the lipopolysaccharide-induced prolactin resistance model, or blocking the prolactin signaling by prolactin receptor-Fc fusion protein, or repressing pituitary prolactin release by dopamine receptor agonist bromocriptine, and found that Notch2-deficient females were more sensitive to these stresses and ended up in pregnancy loss resulting from abnormal corpus luteum function and insufficient serum progesterone level. Overexpression of Prl8a2 in Notch2 knockout mice rescued lipopolysaccharide-induced abortion, highlighting its luteotropic function. Further investigation adopting Rbpj knockout and DNMAML overexpression mouse models along with chromatin immunoprecipitation assay and luciferase analysis confirmed that Prl8a2 was regulated by the canonical Notch signaling. Collectively, our findings demonstrated that decidual prolactin members, under the control of uterine Notch signaling, assisted pituitary prolactin to sustain corpus luteum function and serum progesterone level during post-implantation phase, which was conducive to pregnancy recognition and maintenance.
Author summary Progesterone secreted from the corpus luteum in the ovary is indispensable to pregnancy maintenance in both rodents and humans. Therefore, prolonged corpus luteum lifespan and sustainable progesterone production is a prerequisite for a successful pregnancy. In rodents, in addition to pituitary prolactin and placental lactogens, decidual derived factors have been presumed to possess luteotropic effects during the post-implantation stage. In this study, utilizing a mouse model with uterine specific deletion of Notch2, which displayed decreased level of decidual prolactin member Prl8a2, combined with multiple approaches to interrupt the pituitary prolactin signal, we demonstrated that decidual derived Prl8a2 assisted pituitary prolactin to sustain corpus luteum function and serum progesterone level during post-implantation phase, which was conducive to pregnancy recognition and maintenance. In addition, the expression of decidual Prl8a2 was under the direct control of the canonical Notch pathway. Together, we herein provide convincing evidence that decidual produced Prl8a2, modulated by uterine canonical Notch signaling, exhibits luteotropic functions and contributes to pregnancy maintenance.
Databáze: OpenAIRE
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