Human Fetal Ovary Development Involves the Spatiotemporal Expression of P450c17 Protein

Cole, Beth; Hensinger, Krista; Maciel, Gustavo Arantes Rosa; Chang, R. Jeffery; Erickson, Gregory F.

doi:10.1210/jc.2006-0641

Cited by 52 publications

(39 citation statements)

References 44 publications

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“…Folliculogenesis is initiated in the foetal ovary around 15 weeks after conception when the first primordial follicles are formed [14]. The first primary follicles develop at around 20 weeks of foetal life and maturation to the antral stage is observed during late pregnancy [14,15]. The role of pituitary gonadotrophins in ovarian development and function during foetal life is not well understood.…”

Section: Introductionmentioning

confidence: 99%

Activation of the Hypothalamic-Pituitary-Gonadal Axis in Infancy: Minipuberty

2014

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The hypothalamic-pituitary-gonadal (HPG) axis is active in the midgestational foetus but silenced towards term because of the negative feedback effects mediated by the placental hormones. This restraint is removed at birth, leading to reactivation of the axis and an increase in gonadotrophin levels. Gonadotrophin levels are high during the first 3 months of life but decrease towards the age of 6 months except for FSH levels in girls that remain elevated until 3-4 years of age. After this, the HPG axis remains quiescent until puberty. The postnatal gonadotrophin surge results in gonadal activation in both sexes. In boys, testosterone levels rise to a peak at 1-3 months of age and then decline following LH levels. Postnatal HPG axis activation is associated with penile and testicular growth and therefore considered important for the development of male genitalia. In girls, elevated gonadotrophin levels result in the maturation of ovarian follicles and in an increase in oestradiol levels. Biological significance and possible long-term consequences of this minipuberty remain elusive, as do the mechanisms that silence the HPG axis until puberty. However, the first months of life provide a ‘window of opportunity' for functional studies of the HPG axis prior to pubertal development.

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Section: Introductionmentioning

confidence: 99%

Activation of the Hypothalamic-Pituitary-Gonadal Axis in Infancy: Minipuberty

2014

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“…There are studies that suggest that maternal androgens from PCOS women are passed on to their offspring during gestation trough placental passage and could possibly contribute to higher androgen concentrations during gestation and at birth in PCOS offspring. Others speculate that more androgens are synthesized endogenously by the fetus of PCOS offspring (12,23,24,25,26). The aim of our study is to compare androgen and estrogen concentrations in maternal serum during gestation and in umbilical cord blood, between mothers with PCOS and their offspring compared to non-PCOS mothers and their offspring, using highly specific liquid chromatography tandem mass spectrometry (LC-MS/MS) methods.…”

Section: Introductionmentioning

confidence: 99%

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

Caanen

Kuijper

Hompes

et al. 2016

European Journal of Endocrinology

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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.

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“…21 However, even if the foetal ovary does not produce significant amounts of androgen, the postulate is that the ovary is genetically predisposed to hyperscrete androgen when the hypothalamic-pituitary axis is activated physiologically, either in early post-natal life or at puberty (or indeed both). The consequences of this increased exposure to androgen include abnormalities of LH secretion, 22 and insulin secretion and action, 14,15 which manifest themselves during adolescence ( Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Polycystic ovary syndrome in adolescents

2008

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Background: Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women and typically presents during adolescence. The clinical and biochemical presentation is heterogeneous, but elevated serum concentrations of androgens are the most consistent biochemical abnormality and may be considered to be the hallmark of the syndrome. Many women with PCOS also have insulin resistance and hyperinsulinaemia, which may contribute to the clinical and endocrine abnormalities. The aetiology of PCOS is not clear but studies in the Rhesus monkey suggest that exposure to excess androgen during intrauterine life results in many of the features of human PCOS, including ovarian dysfunction, abnormal LH secretion and insulin resistance. Objective: To review the studies from the literature, including those of the author, regarding aetiology, presentation and management of PCOS in adolescents. Results and conclusions: We have proposed that PCOS in adolescents arises as a result of a genetically determined disorder of ovarian function that results in hyper-secretion of androgens, possibly during fetal life and also during physiological activation of the hypothalamic-pituitary-ovarian in infancy and at the onset of puberty. There is plentiful evidence for a genetic basis for PCOS (it appears to be a complex endocrine disorder resulting from the effects of a several genes), but environmental factors, notably nutrition, influence the clinical and biochemical phenotype. Obesity unmasks or amplifies symptoms, endocrine and metabolic abnormalities. The increasing incidence of childhood obesity has resulted in an alarming Increase not only in distressing symptoms but also impaired glucose tolerance and even diabetes among adolescent girls with PCOS. The search for PCOS genes in this condition, that is not only heterogeneous but also presents only in women of reproductive age, is not straightforward and has produced few convincing candidates so far. In due course, however, identification of the major susceptibility loci is likely to provide key insight into the aetiology of the syndrome and improve diagnosis and management.

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Human Fetal Ovary Development Involves the Spatiotemporal Expression of P450c17 Protein

Abstract: We identified three different classes of P450c17-expressing interstitial cells in the human fetal ovary, each having a different spatiotemporal pattern of P450c17 expression and, presumably, a different set of physiological functions.

Cited by 52 publications

References 44 publications

Activation of the Hypothalamic-Pituitary-Gonadal Axis in Infancy: Minipuberty

Activation of the Hypothalamic-Pituitary-Gonadal Axis in Infancy: Minipuberty

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

Polycystic ovary syndrome in adolescents

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