Gestational Hyperandrogenism in Developmental Programming

Hakim, Christopher; Padmanabhan, Vasantha; Vyas, Arpita

doi:10.1210/en.2016-1801

Cited by 81 publications

(52 citation statements)

References 177 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…IUGR followed by catch‐up growth has been associated with chronic disease later in life, including development of hypertension, impaired glucose tolerance, type 2 diabetes and lipid abnormalities (Barker, ; Valsamakis, Kanaka‐Gantenbein, Malamitsi‐Puchner, & Mastorakos, ). Genetic factors account for one‐third of human IUGR births, and two‐thirds are thought to be secondary to the adverse in utero environment (Valsamakis et al, ), including infection, disease states, nutritional deficit/excess, maternal stress, endocrine abnormalities, smoking or alcohol consumption, and exposure to environmental chemicals (Hakim, Padmanabhan, & Vyas, ).…”

Section: Introductionmentioning

confidence: 99%

“…Genetic factors account for one-third of human IUGR births, and twothirds are thought to be secondary to the adverse in utero environment (Valsamakis et al, 2006), including infection, disease states, nutritional deficit/excess, maternal stress, endocrine abnormalities, smoking or alcohol consumption, and exposure to environmental chemicals (Hakim, Padmanabhan, & Vyas, 2017).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Developmental programming: Sex‐specific programming of growth upon prenatal bisphenol A exposure

Vyas

Veiga-López

et al. 2019

J of Applied Toxicology

Self Cite

View full text Add to dashboard Cite

In both human and animals, in utero exposure to bisphenol A (BPA), an endocrine‐disrupting chemical used in the production of plastics and epoxy resins, has been shown to affect offspring reproductive and metabolic health during adult life. We hypothesized that the effect of prenatal exposure to environmentally relevant doses of BPA will be evident during fetal organogenesis and fetal/postnatal growth trajectory. Pregnant ewes were administered BPA subcutaneously from 30 to 90 days of gestation (term 147 days). Fetal organ weight, anthropometric measures, maternal/fetal hormones and postnatal growth trajectory were measured in both sexes. Gestational BPA administration resulted in higher accumulation in male than female fetuses only at fetal day 65, with minimal impact on fetal/maternal steroid milieu in both sexes at both time points. BPA‐treated male fetuses were heavier than BPA‐treated female fetuses at fetal day 90 whereas this sex difference was not evident in the control group. At the organ level, liver weight was reduced in prenatal BPA‐treated female fetuses, while heart and thyroid gland weights were increased in BPA‐treated male fetuses relative to their sex‐matched control groups. Prenatal BPA treatment also altered the postnatal growth trajectory in a sex‐specific manner. Males grew slower during the early postnatal period and caught up later. Females, in contrast, demonstrated the opposite growth trend. Prenatal BPA‐induced changes in fetal organ differentiation and early life growth strongly implicate translational relevance of in utero contributions to reproductive and metabolic defects previously reported in adult female offspring.

show abstract

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Developmental programming: Sex‐specific programming of growth upon prenatal bisphenol A exposure

Vyas

Veiga-López

et al. 2019

J of Applied Toxicology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Conversely, ovarian dysgenesis does not affect the development of female genitalia. Finally, the third stage of fetal sex differentiation can be disrupted either by a deficient production of testicular hormones (24,25) or an impaired action due to receptor defects (26,27) in the XY fetus, or to an excess androgen exposure in the XX fetus (28)(29)(30). In this review, we will address impaired testicular endocrine function during fetal life resulting in incomplete virilization.…”

Section: Dsd: Abnormal Fetal Sex Differentiationmentioning

confidence: 99%

Male Hypogonadism and Disorders of Sex Development

2020

View full text Add to dashboard Cite

Disorders of Sex Development (DSD) are congenital anomalies in which there is a discordance between chromosomal, genetic, gonadal, and/or internal/external genital sex. In XY individuals, the process of fetal sex differentiation can be disrupted at the stage of gonadal differentiation, resulting in gonadal dysgenesis, a form of early fetal-onset primary hypogonadism characterized by insufficient androgen and anti-Müllerian hormone (AMH) production, which leads to the development of ambiguous or female genitalia. The process of sex differentiation can also be disrupted at the stage of genital differentiation, due to isolated defects in androgen or AMH secretion, but not both. These are forms of fetal-onset hypogonadism with dissociated gonadal dysfunction. In this review, we present a perspective on impaired testicular endocrine function, i.e., fetal-onset male hypogonadism, resulting in incomplete virilization at birth.

show abstract

“…Not surprisingly, therefore, developmental programming has proved a successful strategy for designing the most comprehensive, experimentally induced animal models for PCOS, initiated by prenatally androgenized (PA) female rhesus monkeys [22][23][24]. Progressively increasing evidence of fetal T exposure in daughters of women with PCOS implicates an analogous pathogenic mechanism in women [25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Accelerated Episodic Luteinizing Hormone Release Accompanies Blunted Progesterone Regulation in PCOS-like Female Rhesus Monkeys (Macaca Mulatta) Exposed to Testosterone during Early-to-Mid Gestation

et al. 2018

View full text Add to dashboard Cite

Background/Aims: Ovarian theca cell hyperandrogenism in women with polycystic ovary syndrome (PCOS) is compounded by androgen receptor-mediated impairment of estradiol and progesterone negative feedback regulation of episodic luteinizing hormone (LH) release. The resultant LH hypersecretion, likely the product of accelerated episodic release of gonadotropin-releasing hormone (GnRH) from the median eminence of the hypothalamus, hyperstimulates ovarian theca cell steroidogenesis, enabling testosterone (T) and androstenedione excess. Prenatally androgenized (PA) female monkeys exposed to fetal male levels of T during early-to-mid gestation, when adult, demonstrate PCOS-like traits, including high T and LH levels. This study tests the hypothesis that progesterone resistance-associated acceleration in episodic LH release contributes to PA monkey LH excess. Methods: A total of 4 PA and 3 regularly cycling, healthy control adult female rhesus monkeys of comparable age and body mass index underwent (1) a 10 h, frequent intravenous sampling assessment for LH episodic release, immediately followed by (2) IV infusion of exogenous GnRH to quantify continuing pituitary LH responsiveness, and subsequently (3) an SC injection of a progesterone receptor antagonist, mifepristone, to examine LH responses to blockade of progesterone-mediated action. Results: Compared to controls, the relatively hyperandrogenic PA females exhibited ~100% increase (p = 0.037) in LH pulse frequency, positive correlation of LH pulse amplitude (p = 0.017) with androstenedione, ~100% greater increase (p = 0.034) in acute (0–10 min) LH responses to exogenous GnRH, and an absence (p = 0.008) of modest LH elevation following acute progesterone receptor blockade suggestive of diminished progesterone negative feedback. Conclusion: Such dysregulation of LH release in PCOS-like monkeys implicates impaired feedback control of episodic release of hypothalamic GnRH reminiscent of PCOS neuroendocrinopathy.

show abstract

Gestational Hyperandrogenism in Developmental Programming

Cited by 81 publications

References 177 publications

Developmental programming: Sex‐specific programming of growth upon prenatal bisphenol A exposure

Developmental programming: Sex‐specific programming of growth upon prenatal bisphenol A exposure

Male Hypogonadism and Disorders of Sex Development

Accelerated Episodic Luteinizing Hormone Release Accompanies Blunted Progesterone Regulation in PCOS-like Female Rhesus Monkeys (Macaca Mulatta) Exposed to Testosterone during Early-to-Mid Gestation

Contact Info

Product

Resources

About