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A Modified Technique for Inducing Polycystic Ovary Syndrome in Mice
Published on: July 5, 2024
Impaired microRNA processing causes corpus luteum insufficiency and infertility in mice
Motoyuki Otsuka1, Min Zheng, Masaaki Hayashi
1Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Abstract:
The microRNA (miRNA) processing enzyme Dicer1 is required for zygotic and embryonic development, but the early embryonic lethality of Dicer1 null alleles in mice has limited our ability to address the role of Dicer1 in normal mouse growth and development. To address this question, we used a mouse mutant with a hypomorphic Dicer1 allele (Dicer(d/d)) and found that Dicer1 deficiency resulted in female infertility. This defect in female Dicer(d/d) mice was caused by corpus luteum (CL) insufficiency and resulted, at least in part, from the impaired growth of new capillary vessels in the ovary. We found that the impaired CL angiogenesis in Dicer(d/d) mice was associated with a lack of miR17-5p and let7b, 2 miRNAs that participate in angiogenesis by regulating the expression of the antiangiogenic factor tissue inhibitor of metalloproteinase 1. Furthermore, injection of miR17-5p and let7b into the ovaries of Dicer(d/d) mice partially normalized tissue inhibitor of metalloproteinase 1 expression and CL angiogenesis. Our data indicate that the development and function of the ovarian CL is a physiological process that appears to be regulated by miRNAs and requires Dicer1 function.
Insights
Dicer1 deficiency causes female infertility in mice due to corpus luteum insufficiency and impaired ovarian angiogenesis. Restoring specific microRNAs partially corrected these reproductive defects, highlighting Dicer1
Area of Science:
- Reproductive biology
- Molecular genetics
- Developmental biology
Background:
- Dicer1 enzyme is crucial for microRNA processing and embryonic development.
- Dicer1 null alleles cause early embryonic lethality, hindering study of its role in adult development.
- Hypomorphic Dicer1 alleles allow investigation of Dicer1 function in mature organisms.
Purpose of the Study:
- To investigate the role of Dicer1 in normal mouse growth and development.
- To elucidate the mechanisms underlying female infertility in Dicer1-deficient mice.
- To explore the involvement of microRNAs in ovarian corpus luteum function and angiogenesis.
Main Methods:
- Utilized a hypomorphic Dicer1 mouse mutant (Dicer(d/d)).
- Assessed corpus luteum (CL) function and ovarian angiogenesis in Dicer(d/d) mice.
- Analyzed the expression of specific microRNAs (miR17-5p, let7b) and their target genes.
- Administered miRNA injections into Dicer(d/d) mouse ovaries.
Main Results:
- Dicer1 deficiency in female mice led to infertility.
- Infertility was linked to corpus luteum insufficiency and impaired ovarian angiogenesis.
- Reduced miR17-5p and let7b levels correlated with increased tissue inhibitor of metalloproteinase 1 (TIMP1) expression.
- Ovarian injection of miR17-5p and let7b partially restored CL angiogenesis and normalized TIMP1 levels.
Conclusions:
- Dicer1 function is essential for female reproductive capability.
- MicroRNAs, specifically miR17-5p and let7b, regulate corpus luteum angiogenesis by controlling TIMP1.
- Ovarian corpus luteum development and function are regulated by microRNAs and require Dicer1.
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