title: Size matters: Associations between the androgen receptor CAG repeat length and the intrafollicular hormone milieu.
abstract: Granulosa cell (GC) expressed androgen receptors (AR) and intrafollicular androgens are central to fertility. The transactivating domain of the AR contains a polymorphic CAG repeat sequence, which is linked to the transcriptional activity of AR and may influence the GC function. This study aims to evaluate the effects of the AR CAG repeat length on the intrafollicular hormone profiles, and the gene expression profiles of GC from human small antral follicles. In total, 190 small antral follicles (3-11 mm in diameter) were collected from 58 women undergoing ovarian cryopreservation for fertility preservation. The biallelic mean of the CAG repeat lengths were calculated for each woman, and grouped in three groups: Long CAG repeats (23-26 mean CAG); medium CAG repeats (20.5-22.5 mean CAG) and short CAG repeats (17.5-20.0 mean CAG). The following parameters were measured: follicle diameter, intrafollicular levels of Anti-Müllerian Hormone (AMH), progesterone, oestradiol, testosterone and androstenedione, and GC gene expression levels of FSHR, LHR, AR, CYP19A1, and AMH. The long CAG repeat lengths were associated with significantly decreased testosterone levels, as compared to medium CAG repeats (P = 0.05) and short CAG repeats (P = 0.003). Furthermore, in follicles 3-6 mm in diameter, the long CAG repeats were associated with significantly increased LHR and CYP19A1 gene expression levels compared to short CAG repeat lengths (P = 0.004 and P = 0.04 respectively), and significantly increased LHR expression compared to medium CAG repeat lengths (P = 0.03). In conclusion, long CAG repeat lengths in the AR were associated to significant attenuated levels of androgens and an increased conversion of testosterone into oestradiol, in human small antral follicles.
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark; Laboratory of Reproductive Biology, Rigshospitalet, Copenhagen, Denmark. Electronic address: tanni.kjaer.borgbo@regionh.dk.
authors.forename: T
authors.initials: T
authors.lastname: Borgbo
authors.affiliation: Department of Biology and Medical Genetics, 2nd Faculty of Medicine Charles University, University Hospital Motol, Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Macek
authors.affiliation: Department of Biology and Medical Genetics, 2nd Faculty of Medicine Charles University, University Hospital Motol, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Chrudimska
authors.affiliation: Laboratory of Reproductive Biology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: J V
authors.initials: JV
authors.lastname: Jeppesen
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.
authors.forename: L L
authors.initials: LL
authors.lastname: Hansen
authors.affiliation: Laboratory of Reproductive Biology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: C Yding
authors.initials: CY
authors.lastname: Andersen
mesh_terms: D000293:Adolescent; D000328:Adult; D001141:Aromatase / Q000235:genetics; D005260:Female; D015571:Follicular Fluid / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D042341:Gonadal Hormones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D011944:Receptors, Androgen / Q000235:genetics*; D011974:Receptors, LH / Q000235:genetics; D013739:Testosterone / Q000378:metabolism; D019680:Trinucleotide Repeat Expansion; D055815:Young Adult
chemical_list: C410798:AR protein, human; D042341:Gonadal Hormones; D011944:Receptors, Androgen; D011974:Receptors, LH; D013739:Testosterone; D001141:Aromatase; C561410:CYP19A1 protein, human
keywords: Androgen levels; Androgen receptor; CAG repeats; Follicular fluid; Human small antral follicles