ECE2013 Oral Communications Reproduction (6 abstracts)
The (TAAAA)n polymorphism in the SHBG gene is related to prenatal androgenization of female fetus: possible implications of the developmental origin of metabolic disorders
Christina Pamporaki 1 , Nectaria Xita 1 , Leandros Lazaros 3 , George Makridimas 2 , Ioannis Georgiou 3 , George kolios 4 , Nikolaos Plachouras 2 & Agathocles Tsatsoulis 1
1Department of Endocrinology, Medical School, University of Ioannina, Ioannina, Greece; 2Department of Obstetrics and Gynecology, Medical School, University of Ioannina, Ioannina, Greece; 3Laboratory of Human Reproductive Genetics, Medical School, University of Ioannina, Ioannina, Greece; 4Laboratory of Biochemistry, University Hospital of Ioannina, Ioannina, Greece.
Introduction: The aim of this study was to examine whether the distribution of SHBG (TAAAA)n repeat variants contributes to the exposure of the female fetus to androgen excess, by influencing the, in utero, androgen availability.
Methods: The study population consisted of 100 pregnant women that carried female fetuses and underwent the procedure of amniocentesis due to age (older than 35). Blood samples and amniotic fluid samples were drawn for the measurement of SHBG, testosterone (T) and estradiol (E2). DNA was extracted from peripheral blood leucocytes and amniotic cells and the SHBG (TAAAA)n was genotyped by PCR. 53 of the women enrolled in the study population went into labor few weeks later in the same Department. The exact birth weight of their female neonates was recorded.
Results: Women with long SHBG alleles (8/8, 8/9, 8/10, 9/9, 9/10, 10/10) presented lower levels of SHBG in the amniotic fluid compared to those with short alleles (6/6, 6/7, 6/8, 7/7, 7/8) (P=0.027). Moreover, homozygous for the allele 8, 9 and 10 TAAAA repeats (8/8, 9/9, 10/10) had higher T/SHBG ratio in amniotic fluid than heterozygotes and those with short alleles (P=0.016). A positive correlation between the birth weight of the female neonates and maternal SHBG was also recorded (r=0.292, P=0.032).
Conclusion: The presence of long (TAAAA)n SHBG alleles is associated with lower SHBG levels and higher T/SHBG ratio in the amniotic fluid of female fetuses at midgestation. In addition, lower levels of maternal SHBG are related to lower birth weight of female neonates. Thus, SHBG variants may provide a genetic link to the developmental origin of metabolic disorders and in particular to that of PCOS in women.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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