Developmental programming: postnatal estradiol modulation of prenatally organized reproductive neuroendocrine function in sheep

Puttabyatappa, Muraly; Cardoso, Rodolfo C.; Herkimer, Carol; Veiga-López, Almudena; Padmanabhan, Vasantha

doi:10.1530/rep-16-0065

Cited by 7 publications

(5 citation statements)

References 62 publications

(92 reference statements)

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“…These findings suggest that while modifications occurring during fetal life are critical for programming precocious puberty in female sheep, elevated androgen action postnatally is likely also involved. This is consistent with the premise that environmental, endocrine, and metabolic cues during early postnatal life clearly play a role in controlling the timing of puberty in females [60,68,69]. In regards to the estradiol positive feedback and preovulatory LH surge, while postnatal treatment with an androgen antagonist failed to normalize the timing of the LH surge, it increased the total LH released in response to the estradiol positive feedback challenge to control levels [70].…”

Section: Effects Of Postnatal Interventions On Reproductive and Mesupporting

confidence: 85%

Developmental Programming of PCOS Traits: Insights from the Sheep

Cardoso

Padmanabhan

2019

Medical Sciences

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Polycystic ovary syndrome (PCOS) is a complex disorder that results from a combination of multiple factors, including genetic, epigenetic, and environmental influences. Evidence from clinical and preclinical studies indicates that elevated intrauterine androgen levels increase the susceptibility of the female offspring to develop the PCOS phenotype. Additionally, early postnatal endocrine and metabolic imbalances may act as a “second-hit”, which, through activational effects, might unmask or amplify the modifications programmed prenatally, thus culminating in the development of adult disease. Animal models provide unparalleled resources to investigate the effects of prenatal exposure to androgen excess and to elucidate the etiology and progression of disease conditions associated with this occurrence, such as PCOS. In sheep, prenatal treatment with testosterone disrupts the developmental trajectory of the fetus, culminating in adult neuroendocrine, ovarian, and metabolic perturbations that closely resemble those seen in women with PCOS. Our longitudinal studies clearly demonstrate that prenatal exposure to testosterone excess affects both the reproductive and the metabolic systems, leading to a self-perpetuating cycle with defects in one system having an impact on the other. These observations in the sheep suggest that intervention strategies targeting multiple organ systems may be required to prevent the progression of developmentally programmed disorders.

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Section: Effects Of Postnatal Interventions On Reproductive and Mesupporting

confidence: 85%

Developmental Programming of PCOS Traits: Insights from the Sheep

Cardoso

Padmanabhan

2019

Medical Sciences

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“…Most of the relevant studies in this respect show that E 2 has a potent action in rodents and other animal models such as sheep, during the first few days of postnatal life when the ovarian follicle population is established, and also that it can lead to PCOS‐like features in adult life (Figure ) . Puttabyatappa et al . reported that prenatal E 2 administration in sheep does not reproduce the neuroendocrine disruptions caused by testosterone.…”

Section: Gonadal Steroidsmentioning

confidence: 99%

“…reported that prenatal E 2 administration in sheep does not reproduce the neuroendocrine disruptions caused by testosterone. This indicates that the effects of testosterone on programming reproductive alterations may be caused by androgenic effects during prenatal life and/or that androgens act via oestrogenic pathways as a result of testosterone aromatisation . Puttabyatappa et al .…”

Section: Gonadal Steroidsmentioning

confidence: 99%

“…This indicates that the effects of testosterone on programming reproductive alterations may be caused by androgenic effects during prenatal life and/or that androgens act via oestrogenic pathways as a result of testosterone aromatisation . Puttabyatappa et al . also noted that the dose of E 2 administered was not sufficient to generate a disruption.…”

Section: Gonadal Steroidsmentioning

confidence: 99%

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Developmental programming of the female neuroendocrine system by steroids

Abruzzese

Crisosto

Kempinas

et al. 2018

J Neuroendocrinology

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Developmental programming refers to processes that occur during early life that may have long-term consequences, modulating adult health and disease. Complex diseases, such as diabetes, cancer and cardiovascular disease, have a high prevalence in different populations, are multifactorial, and may have a strong environmental component. The environment interacts with organisms, affecting their behaviour, morphology and physiology. This interaction may induce permanent or long-term changes, and organisms may be more susceptible to environmental factors during certain developmental stages, such as the prenatal and early postnatal periods. Several factors have been identified as responsible for inducing the reprogramming of various reproductive and nonreproductive tissues. Among them, both natural and synthetic steroids, such as endocrine disruptors, are known to have either detrimental or positive effects on organisms depending on the dose of exposure, stage of development and biological sexual background. The present review focuses on the action of steroids and endocrine disruptors as agents involved in developmental programming and on their modulation and effects on female neuroendocrine functions.

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“…47 However, in other species, for example, in sheep and monkeys, the effects of testosterone on programming reproductive alterations might be caused by direct androgenic effects or by an indirect action via estrogenic pathways as a result of testosterone aromatization. [48][49][50] Thereby, the response to androgens in different species needs to be further studied.…”

mentioning

confidence: 99%

Fetal programming by androgen excess in rats affects ovarian fuel sensors and steroidogenesis

Abruzzese

Heber

Arboccó

et al. 2019

J Dev Orig Health Dis

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Fetal programming by androgen excess is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS is more than a reproductive disorder, as women with PCOS also show metabolic and other endocrine alterations. Since both ovarian and reproductive functions depend on energy balance, the alterations in metabolism may be related to reproductive alterations. The present study aimed to evaluate the effect of androgen excess during prenatal life on ovarian fuel sensors and its consequences on steroidogenesis. To this end, pregnant rats were hyperandrogenized with testosterone and the following parameters were evaluated in their female offspring: follicular development, PPARG levels, adipokines (including leptin, adiponectin, and chemerin as ovarian fuel sensors), serum gonadotropins (LH and FSH), the mRNA of their ovarian receptors, and the expression of steroidogenic mediators. At 60 days of age, the prenatally hyperandrogenized (PH) female offspring displayed both an irregular ovulatory phenotype and an anovulatory phenotype with altered follicular development and the presence of cysts. Both PH groups showed altered levels of both proteins and mRNA of PPARG and a different expression pattern of the adipokines studied. Although serum gonadotropins were not impaired, there were alterations in the mRNA levels of their ovarian receptors. The steroidogenic mediators Star, Cyp11a1, Cyp17a1, and Cyp19a1 were altered differently in each of the PH groups. We concluded that androgen excess during prenatal life leads to developmental programming effects that affect ovarian fuel sensors and steroidogenesis in a phenotype-specific way.

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Developmental programming: postnatal estradiol modulation of prenatally organized reproductive neuroendocrine function in sheep

Cited by 7 publications

References 62 publications

Developmental Programming of PCOS Traits: Insights from the Sheep

Developmental Programming of PCOS Traits: Insights from the Sheep

Developmental programming of the female neuroendocrine system by steroids

Fetal programming by androgen excess in rats affects ovarian fuel sensors and steroidogenesis

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