Effect of the FSH receptor single nucleotide polymorphisms (FSHR 307/680) on the follicular fluid hormone profile and the granulosa cell gene expression in human small antral follicles.
The most pronounced effects of FSH signalling are potentially displayed in the follicle fluid, which acts as a reservoir for FSH-induced granulosa cell (GC) secreted hormones. This study investigates the effects of two common polymorphisms of FSHR, FSHR 307 (rs6165) and FSHR 680 (rs6166), by evaluating the hormone and gene expression profiles of human small antral follicles collected under physiological conditions in connection with fertility preservation. In total 69 women at various time during the menstrual cycle were included in this study. The intrafollicular hormone content of 179 follicular fluid samples and the gene expression levels of 85 GC samples were correlated to the genotype of both FSHR polymorphisms. The following parameters were evaluated: follicle diameter, levels of Anti-Müllerian hormone (AMH), progesterone, estradiol, testosterone and androstenedione and gene expression levels of FSHR, luteinizing hormone receptor (LHR), androgen receptor, aromatase cytochrome p450 (CYP19A1), AMH and AMH receptor II (AMHR2). There was 100% concordance between the FSHR 307 and the FSHR 680 genotypes: A/A (p.307Thr/Thr and p.680Asn/Asn), A/G (p.307Thr/Ala and p.680Asn/Ser) and G/G (p.307Ala/Ala and p.680Ser/Ser). Considering all follicles, compared with the other genotypes the G/G genotype was associated with significantly elevated gene expression levels for LHR, while AMHR2 gene expression levels were significantly reduced. In follicles 3-6 mm in diameter LHR gene expression was significantly increased, whereas AMH gene expression was significantly reduced for the G/G genotype. In follicles >6 mm, estradiol and CYP19A1 gene expression levels were significantly higher for the G/G genotype. In conclusion, significant changes were observed between the FSHR 307/680 polymorphisms in human small antral follicles collected under physiological FSH conditions.
Laboratory of Reproductive Biology, Rigshospitalet, Copenhagen, Denmark Department of Biomedicine, University of Aarhus, Aarhus, Denmark tanni.kjaer.borgbo@regionh.dk.
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T
Borgbo
Laboratory of Reproductive Biology, Rigshospitalet, Copenhagen, Denmark.
J V
JV
Jeppesen
Molecular Genetic Reproductive Medicine, Department of Clinical Sciences, Lund University, Malmö, Sweden.
I
I
Lindgren
Molecular Genetic Reproductive Medicine, Department of Clinical Sciences, Lund University, Malmö, Sweden.
Y
Y
Lundberg Giwercman
Department of Biomedicine, University of Aarhus, Aarhus, Denmark.
L L
LL
Hansen
Laboratory of Reproductive Biology, Rigshospitalet, Copenhagen, Denmark.
C
C
Yding Andersen
D000293:Adolescent; D000328:Adult; D000735:Androstenedione / Q000378:metabolism; D054304:Anti-Mullerian Hormone / Q000235:genetics / Q000378:metabolism; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D048429:Cell Size; D004958:Estradiol / Q000378:metabolism; D005260:Female; D015571:Follicular Fluid / Q000737:chemistry / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005838:Genotype; D042341:Gonadal Hormones / Q000235:genetics* / Q000378:metabolism; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008597:Menstrual Cycle / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D011374:Progesterone / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D011962:Receptors, FSH / Q000235:genetics* / Q000378:metabolism; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
D042341:Gonadal Hormones; D011944:Receptors, Androgen; D011962:Receptors, FSH; D011974:Receptors, LH; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; C084621:anti-Mullerian hormone receptor; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D004958:Estradiol; D054304:Anti-Mullerian Hormone; D001141:Aromatase; C561410:CYP19A1 protein, human
FSHR 307/680; FSHR polymorphisms; follicular fluid; granulosa cell gene expression; sex steroids