Fetal Estrogens are not Involved in Sex Determination But Critical for Early Ovarian Differentiation in Rabbits

AROMATASE is encoded by the CYP19A1 gene and is the cytochrome enzyme responsible for estrogen synthesis in vertebrates. In most mammals, a peak of CYP19A1 gene expression occurs in the fetal XX gonad when sexual differentiation is initiated. To elucidate the role of this peak, we produced 3 lines o...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2022-01, Vol.163 (1), p.1
Main Authors: Jolivet, Geneviève, Daniel-Carlier, Nathalie, Harscoët, Erwana, Airaud, Eloïse, Dewaele, Aurélie, Pierson, Cloé, Giton, Frank, Boulanger, Laurent, Daniel, Nathalie, Mandon-Pépin, Béatrice, Pannetier, Maëlle, Pailhoux, Eric
Format: Article
Language:English
Subjects:
17β-Estradiol
Analysis
Animals
Anti-Mullerian Hormone - metabolism
Aromatase
Cell Differentiation
Cell Proliferation
Cytochrome P450 Family 19 - metabolism
Development Biology
Differentiation
Endocrinology
Enzymes
Estradiol
Estradiol - metabolism
Estrogens
Estrogens - metabolism
Female
Fetuses
Follicles
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Developmental
Germ cells
Gonads
INDEL Mutation
Life Sciences
Meiosis
Ovarian Follicle - physiology
Ovaries
Ovary - embryology
Ovary - physiology
Ovulation
Phenotype
Rabbits
Sex determination
Sex Determination Processes - physiology
Sex determination, Diagnostic
Sex differentiation
Sex Differentiation - physiology
Sex hormones
Testosterone - metabolism
Transcriptomics
Vertebrates
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Summary:AROMATASE is encoded by the CYP19A1 gene and is the cytochrome enzyme responsible for estrogen synthesis in vertebrates. In most mammals, a peak of CYP19A1 gene expression occurs in the fetal XX gonad when sexual differentiation is initiated. To elucidate the role of this peak, we produced 3 lines of TALEN genetically edited CYP19A1 knockout (KO) rabbits that were devoid of any estradiol production. All the KO XX rabbits developed as females with aberrantly small ovaries in adulthood, an almost empty reserve of primordial follicles, and very few large antrum follicles. Ovulation never occurred. Our histological, immunohistological, and transcriptomic analyses showed that the estradiol surge in the XX fetal rabbit gonad is not essential to its determination as an ovary, or for meiosis. However, it is mandatory for the high proliferation and differentiation of both somatic and germ cells, and consequently for establishment of the ovarian reserve.
ISSN:0013-7227
1945-7170
DOI:10.1210/endocr/bqab210