Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome

Abstract

Objective: Little is known about the aetiology of polycystic ovary syndrome (PCOS). Some suggest that elevated maternal androgens during gestation play a causative role. This implies placental passage of androgens during pregnancy. The aim of this study is to compare androgen and estrogen concentrations in maternal serum during pregnancy and in umbilical cord blood, between mothers with PCOS and their offspring compared to controls. Design: Prospective case-control study. Methods: Maternal blood samples were collected around 20 weeks of gestation and at delivery. Umbilical cord blood was also taken at delivery. Androgens (testosterone (T), androstenedione (ADION), dehydroepiandrostenedione (DHEA)) and estrogens (estrone (E 1 ), estradiol (E 2 ), estriol (E 3 )) were measured using the liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. Results: At 20 weeks of gestation: T (PZ0.019) and ADION (PZ0.034) were higher in the PCOS mothers (pregnant with a girl), whereas DHEA, E 1 , E 2 , and E 3 were not different. Maternal concentration at birth: T (PZ0.004) and ADION (PZ0.009) were also higher in the subgroup of PCOS mothers that were pregnant with a girl compared to the girl pregnancy controls. DHEA, E 1 , E 2 and E 3 were not different. In umbilical cord blood, no differences were found for T, ADION, DHEA, E 2 , E 3 , and AMH between the PCOS mothers and the controls respectively. E 1 was lower in girls from PCOS mothers (PZ0.007). Conclusions: Despite elevated maternal androgen concentrations during pregnancy in PCOS mothers, offspring showed no signs of elevated androgen concentrations in cord blood at birth using the latest highly specific LC-MS/MS methods.

Circulating antimüllerian hormone and steroid hormone levels remain high in pregnant women with polycystic ovary syndrome at term

“…Moreover, the levels of AMH, T, A, and E 2 were significantly higher in women with PCOS carrying a female fetus when compared with controls with a female fetus, and no differences were found between groups in pregnancies with male fetuses. In line with this, Caanen et al (44) have also detected higher T and A concentrations in maternal circulation throughout the pregnancies of women with PCOS who are carrying a female fetus, but no fetal gender-specific differences in maternal serum androgen concentrations in women with PCOS were detected in a third study (36). Additional studies that support the idea of fetal gender influencing maternal steroid levels also exist: Maliqueo et al (45) reported fetal gender-specific differences in placental aromatase expression, and Kallak et al (27) detected a maternal AMH genotype correlating with maternal T levels in pregnancies with a male fetus.…”

Ontogeny and reversal of brain circuit abnormalities in a preclinical model of PCOS

“…In women, although the route of fetal exposure is not clearly defined, elevated maternal testosterone levels are linked to the development of PCOS in their daughters (21,47). Serum testosterone levels increase by approximately 70% in pregnancy (48), and maternal testosterone is even greater in women with PCOS (49,50). It is well known that the architecture of the fetal mammalian brain is exquisitely sensitive to androgen exposure and can program adult physiology (51).…”

Translational Insight Into Polycystic Ovary Syndrome (PCOS) From Female Monkeys with PCOS-like Traits

“…In addition, since pregnant PCOS women have elevated circulating T levels [86, 87], subtle reductions in placental aromatase [88] may expose female offspring to elevated T during gestation. Interestingly, elevated mid-gestation serum T levels in PCOS mothers predict in their adolescent daughters elevated levels of AMH, a transforming growth factor-β (TGF-β) superfamily protein normally produced by granulosa cells of preantral and small antral ovarian follicles [89].…”

“…In studies of umbilical cord venous blood levels in newborn daughters born to women with PCOS, one study shows elevated T levels [92], whereas two studies show reduced androstenedione levels [88, 93] and one shows normal T levels [87]. In a fourth study involving adolescent girls diagnosed with PCOS, and including an inherently high prevalence (~28%) of diagnosis at this young age, umbilical cord blood shows no elevation in T levels [94].…”