Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/59885
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Type: Journal article
Title: Reproductive biology of female Bmal1 null mice
Author: Boden, M.
Varcoe, T.
Voultsios, A.
Kennaway, D.
Citation: Reproduction, 2010; 139(6):1077-1090
Publisher: Bio Scientifica Ltd
Issue Date: 2010
ISSN: 1470-1626
1741-7899
Statement of
Responsibility: 
Michael J. Boden, Tamara J. Varcoe, Athena Voultsios and David J. Kennaway
Abstract: The light/dark cycle and suprachiasmatic nucleus rhythmicity are known to have important influences on reproductive function of rodents. We studied reproductive function in female heterozygous and homozygous brain and muscle ARNT-like protein 1 (Bmal1, also known as Arntl) null mice, which lack central and peripheral cellular rhythms. Heterozygous Bmal1 mice developed normally and were fertile, with apparent normal pregnancy progression and litter size, although postnatal mortality up to weaning was high (1.1–1.3/litter). The genotype distribution was skewed with both heterozygous and null genotypes underrepresented (1.0:1.7:0.7; P<0.05), suggesting loss of a single Bmal1 allele may impact on postnatal survival. Homozygous Bmal1 null mice were 30% lighter at weaning, and while they grew at a similar rate to the wild-type mice, they never achieved a comparable body weight. They had delayed vaginal opening (4 days), disrupted estrus cyclicity, and reduced ovarian weight (30%). Bmal1 null mice had a 40% reduction in ductal length and a 43% reduction in ductal branches in the mammary gland. Surprisingly, the Bmal1 mice ovulated, but progesterone synthesis was reduced in conjunction with altered corpora lutea formation. Pregnancy failed prior to implantation presumably due to poor embryo development. While Bmal1 null ovaries responded to pregnant mare serum gonadotropin/human chorionic gonadotropin stimulation, ovulation rate was reduced, and the fertilized oocytes progressed poorly to blastocysts and failed to implant. The loss of Bmal1 gene expression resulted in a loss of rhythmicity of many genes in the ovary and downregulation of Star. In conclusion, it is clear that the profound infertility of Bmal1 null mice is multifactorial.
Keywords: Ovary; Vagina; Mammary Glands, Animal; Animals; Mice, Knockout; Mice; Infertility, Female; Body Weight; Progesterone; Chorionic Gonadotropin; Gonadotropins, Equine; RNA, Messenger; Organ Size; Gene Expression; Weaning; Embryonic Development; Reproduction; Estrous Cycle; Ovulation; Pregnancy; Litter Size; Sexual Maturation; Heterozygote; Homozygote; Female; ARNTL Transcription Factors
Rights: Copyright © 2010 Society for Reproduction and Fertility
RMID: 0020095235
DOI: 10.1530/REP-09-0523
Appears in Collections:Obstetrics and Gynaecology publications

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