Loss of microRNA-7a2 induces hypogonadotropic hypogonadism and infertility

Autor: Mathieu Latreille, Markus Stoffel, Emanuel Gasser, Mary P. LaPierre, Yinjie Yang, Kashan Ahmed, Jukka Kero, Thomas Rülicke, Rémy Denzler
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Hypothalamo-Hypophyseal System
Sialoglycoproteins
Immunology
Prostaglandin
030209 endocrinology & metabolism
Ovary
Bone Morphogenetic Protein 4
Biology
ta3111
03 medical and health sciences
chemistry.chemical_compound
Follicle-stimulating hormone
Mice
0302 clinical medicine
Hypogonadotropic hypogonadism
Internal medicine
Testis
medicine
Animals
Receptor
Gonadal Steroid Hormones
Mice
Knockout
Hypogonadism
General Medicine
11 Medical And Health Sciences
Luteinizing Hormone
medicine.disease
Receptors
Fibroblast Growth Factor
MicroRNAs
030104 developmental biology
Endocrinology
medicine.anatomical_structure
chemistry
Infertility
Female
Signal transduction
Follicle Stimulating Hormone
Luteinizing hormone
Hormone
Signal Transduction
Research Article
Popis: MicroRNAs (miRNAs) are negative modulators of gene expression that fine-tune numerous biological processes. miRNA loss-of-function rarely results in highly penetrant phenotypes, but rather, influences cellular responses to physiologic and pathophysiologic stresses. Here, we have reported that a single member of the evolutionarily conserved miR-7 family, miR-7a2, is essential for normal pituitary development and hypothalamic-pituitary-gonadal (HPG) function in adulthood. Genetic deletion of mir-7a2 causes infertility, with low levels of gonadotropic and sex steroid hormones, small testes or ovaries, impaired spermatogenesis, and lack of ovulation in male and female mice, respectively. We found that miR-7a2 is highly expressed in the pituitary, where it suppresses golgi glycoprotein 1 (GLG1) expression and downstream bone morphogenetic protein 4 (BMP4) signaling and also reduces expression of the prostaglandin F2a receptor negative regulator (PTGFRN), an inhibitor of prostaglandin signaling and follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion. Our results reveal that miR-7a2 critically regulates sexual maturation and reproductive function by interconnecting miR-7 genomic circuits that regulate FSH and LH synthesis and secretion through their effects on pituitary prostaglandin and BMP4 signaling.
Databáze: OpenAIRE
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