Pervasive developmental disorders in children of hyperandrogenic women with polycystic ovary syndrome: a longitudinal case–control study

Palomba, Stefano; Marotta, Rosa; Cello, Annalisa Di; Russo, Tiziana; Falbo, Angela; Orio, Francesco; Tolino, Achille; Zullo, Fulvio; Esposito, Rosa; Sala, Giovanni Battista La

doi:10.1111/j.1365-2265.2012.04443.x

Cited by 125 publications

(120 citation statements)

References 31 publications

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“…It has been suggested that children born from hyperandrogenic women may express more autistic traits and might be under a higher risks for autism [11]. In one of our previous studies, we have also shown that mothers of autistic children had higher levels of testosterone in plasma [12].…”

Section: Introductionmentioning

confidence: 69%

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Prenatal hyperandrogenic environment induced autistic-like behavior in rat offspring

Zhang

Shou

et al. 2015

Physiology & Behavior

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Section: Introductionmentioning

confidence: 69%

“…Recent studies revealed that environmental factors, especially the intrauterine developmental environment, played important roles in the development of ASD [11,30,31]. Clinical evidence also suggested that dysregulation of brain development in ASD may begin at prenatal developmental stages [32].…”

Section: Discussionmentioning

confidence: 98%

Prenatal hyperandrogenic environment induced autistic-like behavior in rat offspring

Zhang

Shou

et al. 2015

Physiology & Behavior

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“…1 -5 In the case of gestational hyperandrogenemia, polycystic ovary syndrome (PCOS), gestational luteoma 6 , or hyperreactio luteinalis, 7 the fetus may also be exposed to high levels of testosterone from the maternal circulation. 8 , 9 Hyperandrogenism during pregnancy causes fetal virilization, 10 , 11 intrauterine growth restriction, 12 and low birth weight. 13 These prenatal complications positively correlate with the development in adulthood of hyperinsulinemia 14 , 15 and metabolic disorders such as obesity, 16 , 17 hypertension, 18 and PCOS.…”

Section: Introductionmentioning

confidence: 99%

Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

et al. 2018

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Background: Conditions of excess androgen in women, such as polycystic ovary syndrome (PCOS), often exhibit intergenerational transmission. One way in which the risk for PCOS may be increased in daughters of affected women is through exposure to elevated androgens in utero. Hyperandrogenemic conditions have serious health consequences, including increased risk for hypertension and cardiovascular disease. Recently, gut dysbiosis has been found to induce hypertension in rats, such that blood pressure can be normalized through fecal microbial transplant. Therefore, we hypothesized that the hypertension seen in PCOS has early origins in gut dysbiosis caused by in utero exposure to excess androgen. We investigated this hypothesis with a model of prenatal androgen (PNA) exposure and maternal hyperandrogenemia by single-injection of testosterone cypionate or sesame oil vehicle (VEH) to pregnant dams in late gestation. We then completed a gut microbiota and cardiometabolic profile of the adult female offspring. Results: The metabolic assessment revealed that adult PNA rats had increased body weight and increased mRNA expression of adipokines: adipocyte binding protein 2, adiponectin, and leptin in inguinal white adipose tissue. Radiotelemetry analysis revealed hypertension with decreased heart rate in PNA animals. The fecal microbiota profile of PNA animals contained higher relative abundance of bacteria associated with steroid hormone synthesis, Nocardiaceae and Clostridiaceae, and lower abundance of Akkermansia, Bacteroides, Lactobacillus, Clostridium. The PNA animals also had an increased relative abundance of bacteria associated with biosynthesis and elongation of unsaturated short chain fatty acids (SCFAs). Conclusions: We found that prenatal exposure to excess androgen negatively impacted cardiovascular function by increasing systolic and diastolic blood pressure and decreasing heart rate. Prenatal androgen was also associated with gut microbial dysbiosis and altered abundance of bacteria involved in metabolite production of short chain fatty acids. These results suggest that early-life exposure to hyperandrogenemia in daughters of women with PCOS may lead to long-term alterations in gut microbiota and cardiometabolic function.

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“…For example, psychological stress in women correlates with testosterone concentration (Chichinadze and Chichinadze, 2008;Lennartsson et al, 2012), and maternal stress during pregnancy is associated with increased risk of ASD in children (Keefe, 2002). Polycystic ovary syndrome (PCOS), characterized by ovarian dysfunction and polycystic ovarian morphology in women of childbearing age, is also associated with hyperandrogenism (Abbott et al, 2005;Azziz et al, 2005;Franks, 1995;Goodarzi et al, 2011), and it has been suggested that children from PCOS mothers may express more autistic traits (Palomba et al, 2012). An animal model study of maternal hyperandrogenism during pregnancy has demonstrated that the offspring exhibit autistic-like behavior from early childhood into adulthood (Xu et al, 2015).…”

Section: Introductionmentioning

confidence: 98%

Abnormal instability, excess density, and aberrant morphology of dendritic spines in prenatally testosterone-exposed mice

Hatanaka

Wada

Kabuta

2015

Neurochemistry International

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Fetal brain development is programmed by the maternal intrauterine environment, and disturbance of the in utero environment leads to persisting deficits in brain functions of the offspring. Testosterone is an intrauterine environmental factor, and plays significant roles in fetal development. From human and animal model studies, it has been suggested that increased intrauterine testosterone concentration triggers subsequent autistic-like behavior of the offspring; however, the effects of maternal excess testosterone on synaptic development of the offspring remain unknown. In the present study, we employed prenatally testosterone-exposed mice, and by using in vivo two-photon imaging, we analyzed the dynamics, density, and morphology of the dendritic spine, an excitatory postsynaptic structure. We found that the offspring from testosterone-treated dams showed abnormal synaptic instability persisting into young adulthood, whereas dendritic spines in control mice became stabilized with normal synaptic maturation. In prenatally testosterone-exposed mice, the density of dendritic spines was excessively increased, and their morphology was abnormal. These results suggest that prenatally testosterone-exposed mice may have deficits in synaptic development, and furthermore that the observed pathological features of their dendritic spines may be the cause of the synaptic pathogenesis in prenatally testosterone-exposed mice.

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Pervasive developmental disorders in children of hyperandrogenic women with polycystic ovary syndrome: a longitudinal case–control study

Abstract: Daughters of mothers affected by hyperandrogenic PCOS seem to have a higher risk for PDDs probably due to an unbalanced prenatal exposure to high levels of testosterone.

Cited by 125 publications

References 31 publications

Prenatal hyperandrogenic environment induced autistic-like behavior in rat offspring

Prenatal hyperandrogenic environment induced autistic-like behavior in rat offspring

Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

Abnormal instability, excess density, and aberrant morphology of dendritic spines in prenatally testosterone-exposed mice

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