Molecular insights into androgen actions in male and female reproductive function from androgen receptor knockout models

Walters, Kirsty A; Simanainen, Ulla; Handelsman, David J.

doi:10.1093/humupd/dmq003

Cited by 162 publications

(103 citation statements)

References 133 publications

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“…Although heterozygote females initially display similar fertility to wild-type females, they exhibit recurrent spontaneous miscarriages and this indicates that quantitative variations in AR activity via gene dosage may play a role in determining female fertility [25]. Our findings are comparable with study performed by Karvela et al They managed a case-control study with 131women with RSA and found that there are significant differences between the two groups in terms of both genotype distribution and allele frequencies (2008).…”

Section: Resultssupporting

confidence: 88%

StuI polymorphism on the androgen receptor gene is associated with recurrent spontaneous abortion

Jahaninejad

Ghasemi

Kalantar

et al. 2013

J Assist Reprod Genet

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Purpose This is a case-control study to determine whether G1733A polymorphism of androgen receptor gene is associated with an increased risk for recurrent spontaneous abortion (RSA). Method A total of 85 women with at least two recurrent spontaneous abortion before 20th week of gestation composed the study group. Subjects were genotyped by the polymerase chain reaction restriction fragment length polymorphism method. Results The observed frequencies of GG, GA and AA genotypes of the G1733A polymorphism were 5.89 %, 82.35 % and 11.76 %, respectively, for the patient group and 71.76 %, 23.51 % and 4.71 %, respectively, for the control group. Allele frequencies of the G1733A polymorphism among patients and controls were 0.47 and 0.84, respectively, for the dominant allele (G) (wild type) and 0.53 and 0.16, respectively, for the A allele (mutant type). Conclusions These results indicated that the androgen receptor G1733A polymorphism is strongly associated with increased risk for RSA.Keywords Recurrent spontaneous abortion . Androgen receptor . Polymorphism . RFLP PCR Recurrent spontaneous abortion (RSA) is a reproductive problem that occurs in women in reproductive age with a frequency of 1 %-3 % [20]. It is defined as two or more repeated pregnancy losses before the 20th week of gestation [14]. The risk of miscarriage is enhanced by a variety of factors including chromosomal abnormalities, uterine abnormalities, hereditary thrombophilia, endocrinologic disorders,-immunologic factors, infections, and nutritional and environmental factors [18,19]. In women with a history of recurrent miscarriage, the risk of miscarriage in a subsequent pregnancy is about 40 % to 50 %. It has a major influence on the wellbeing and psychological status of patients, therefore improved diagnosis and development of treatment strategies is essential [6,16,23]. In the past years, research interest has been focused on the association studies between different genetic polymorphisms and recurrent spontaneous abortion.Androgens are lipophilic hormones with several physiological effects in both sexes [17]. Androgen signaling in female is very important for the differentiation of human endometrial stromal cells into decidual cell; a process is called decidualization that critically controls embryo implantation and placentation [11]. The effect of androgens such as testosterone and dihydrotestosterone mediated by androgen receptor (AR) that is a nuclear receptor [3]. Androgen receptor is widely expressed in female reproductive tissue such as endometrium [1] and binds to a steroid ligand and then is transferred into the nucleus, where it regulates the transcription of androgen-responsive genes [5]. The AR gene is located on the X chromosome between q11 and q12 loci and is composed of eight exons [2] that encode a 110-kd protein that contains an N-terminal transactivation domain, Capsule Our results indicated that the androgen receptor G1733A polymorphism is strongly associated with increased risk for RSA.T. Jahaninejad (*) :

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Section: Resultssupporting

confidence: 88%

StuI polymorphism on the androgen receptor gene is associated with recurrent spontaneous abortion

Jahaninejad

Ghasemi

Kalantar

et al. 2013

J Assist Reprod Genet

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“…Studies on murine models of conditional granulosa cell and oocyte-specific deletion of the androgen receptor found positive correlations between androgen receptor and FSH receptor expression, suggesting that androgens may prevent preantral follicle growth and atresia [16][17][18][19][20]. Similarly, it has recently been shown that androgen receptor mRNA and androgen levels in follicular fluid correlate with FSH receptor mRNA expression in human granulosa cells from small antral follicles [21]. Androgens also increase insulin-like growth factor 1 (IGF-1) expression in the primate ovary, which plays an essential role in regulating follicular development [22][23][24].…”

Section: Discussionmentioning

confidence: 98%

Basal serum testosterone levels correlate with ovarian response but do not predict pregnancy outcome in non-PCOS women undergoing IVF

Sun

Wang

Sun

et al. 2014

J Assist Reprod Genet

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Purpose To evaluate basal testosterone (T) levels in women undergoing in vitro fertilization (IVF) cycles and examine the association between basal T levels and ovarian response or IVF pregnancy outcome. Methods We retrospectively analyzed 1413 infertile Chinese women undergoing their first IVF treatment at our institution's reproductive center from March 2011 to May 2013. The basal testosterone (T) levels in women undergoing in vitro fertilization (IVF) and the relationship between basal T levels and ovarian response or IVF pregnancy outcome were determined. These patients did not have polycystic ovary syndrome (PCOS) or endometriosis, and were treated with a long luteal down-regulation protocol. Subjects were divided into 2 groups according to basal testosterone (T) levels: Group 1, basal T values <20 ng/dl (n=473), and Group 2, basal T values >20 ng/dl (n=940). We evaluated the association of basal T levels with ovarian response and IVF outcome in the two groups. Results In this study, BMI, basal follicle-stimulating hormone (FSH) levels, basal luteinizing hormone (LH) levels, antral follicle count (AFC), days of stimulation, total gonadotrophin dose, basal FSH/LH ratio, and the number of follicles >14 mm were significantly different (P<0.05) between the two groups. Basal T level positively correlated with ovarian reserve function, number of follicles >14 mm on human chorionic gonadotrophin (HCG) day, and total gonadotropin dose. However, basal T levels play no role in predicting IVF pregnancy outcome. Conclusion Basal T level can be used as a good predictor for ovarian response and the number of large follicles on HCG day. Additionally, we may use basal T level as a marker to predict FSH dosage. In general women, lower level of T might relate with potential poor ovarian response. However, based on our data, basal T levels do not predict pregnancy outcome.

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“…The promoter region of p21 contains an ARE and, therefore, the AR likely regulates its expression. The marked reduction in p21 expression in the Ar-null ovary during the peri-ovulatory stage may disturb the process of terminating proliferation and explain the increased cell apoptosis and follicular atresia in these Ar 2 K/K mice (Hu et al 2004, Walters et al 2010.…”

Section: Ar-induced Genes In Follicular Developmentmentioning

confidence: 99%

Androgen actions in the ovary: balance is key

Prizant

Gleicher

Sen

2014

Journal of Endocrinology

120

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For many decades, elevated androgens in women have been associated with poor reproductive health. However, recent studies have shown that androgens play a crucial role in women's fertility. The following review provides an overall perspective about how androgens and androgen receptor-mediated actions regulate normal follicular development, as well as discuss emerging concepts, latest perceptions, and controversies regarding androgen actions and signaling in the ovary.

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Molecular insights into androgen actions in male and female reproductive function from androgen receptor knockout models

Cited by 162 publications

References 133 publications

StuI polymorphism on the androgen receptor gene is associated with recurrent spontaneous abortion

StuI polymorphism on the androgen receptor gene is associated with recurrent spontaneous abortion

Basal serum testosterone levels correlate with ovarian response but do not predict pregnancy outcome in non-PCOS women undergoing IVF

Androgen actions in the ovary: balance is key

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