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

TY - JOUR

T1 - 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

AU - Borgbo, T

AU - Jeppesen, J V

AU - Lindgren, I

AU - Lundberg Giwercman, Y

AU - Hansen, L L

AU - Andersen, Claus Yding

N1 - © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: [email protected].

PY - 2014/9/23

Y1 - 2014/9/23

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Androstenedione

KW - Anti-Mullerian Hormone

KW - Aromatase

KW - Cell Size

KW - Estradiol

KW - Female

KW - Follicular Fluid

KW - Gene Expression Profiling

KW - Gene Expression Regulation

KW - Genotype

KW - Gonadal Hormones

KW - Granulosa Cells

KW - Humans

KW - Menstrual Cycle

KW - Polymorphism, Single Nucleotide

KW - Progesterone

KW - Receptors, Androgen

KW - Receptors, FSH

KW - Receptors, LH

KW - Receptors, Peptide

KW - Receptors, Transforming Growth Factor beta

KW - Testosterone

U2 - 10.1093/molehr/gau106

DO - 10.1093/molehr/gau106

M3 - Journal article

C2 - 25403644

SN - 1360-9947

VL - 21

SP - 255

EP - 261

JO - Molecular Human Reproduction

JF - Molecular Human Reproduction

IS - 3

ER -