Developmental programming of the female neuroendocrine system by steroids

Abstract

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.

Hyperandrogenism and Polycystic ovary syndrome: Effects in pregnancy and offspring development

“…In this regard, it has been shown that altered patterns of DNA methylation and impaired gene expression of steroidogenic genes, among others, could be responsible for maternal hyperandrogenism that may affect the fetus during in utero life leading to developmental programming effects (Filippou & Homburg, 2017). The hypothesis of the developmental origins of PCOS by prenatal androgen exposure (Abbott et al, 2002) is widely supported by different animal models, including monkeys, sheep, and rodents (reviewed in Abruzzese et al, 2018; Stener‐Victorin et al, 2020). Moreover, evidence from patients has also shown that pregnant PCOS women present hyperandrogenism, increased AMH levels and altered CYP19 (aromatase) placental expression (Maliqueo et al, 2013; Sir‐Petermann et al, 2002; Tata et al, 2018).…”

“…In accordance with this, one of the most accepted animal models of PCOS is the intrauterine androgen excess model. In this animal model, pregnant females are exposed to high androgens levels through testosterone or DHT injections during different periods of pregnancy (reviewed in Abruzzese et al, 2018). By using these animals' models, metabolic, endocrine and reproductive outcomes have been studied in the Filial 0 (exposed animals) and their offspring (Filial 1, F1); however, there are only few studies that focused on the subsequent generations (Figure 6).…”

“…PCOS is considered a multifactorial syndrome in which both genetic susceptibility and environmental factors play a role in its development and phenotypic manifestation. Among the environmental factors, it has been studied in different animal models and humans that an altered hormonal profile during prenatal and/or perinatal life contributes to PCOS development (Abruzzese et al, 2018). Estrogens, androgens and the anti-Müllerian hormone (AMH) are the main hormones described to contribute to PCOS development.…”

Neuroendocrine regulation of reproduction, stress, inflammation and energy homeostasis

“…The cellular pathways mediating rapid glucocorticoid signalling in negative feedback effects are also discussed. The effects of steroids and endocrine disruptors during development and their long‐term consequences are extensively discussed in the review by Abruzzese et al Last but not least, the review by Avalos et al discusses the involvement of hypothalamic epigenetic mechanisms in the control of energy homeostasis and feeding behaviours.…”

Fetal programming in beef cattle: isotopic, metabolomic and phenotypic effects

“…According to Moreira et al (2019), fetal programming is a concept that encompasses adaptation mechanisms in which nutrition during the gestational period and the uterine environment influence fetal development, which can lead to permanent phenotypic changes in the progeny. However, the concept of fetal programming goes beyond just nutritional stimuli, being pointed out in several studies as any process that has an influence on the pregnant female and can have consequences for the fetus and in the long term in the progeny (BARKER et al, 1993;LUCAS;FEWTRELL;COLE, 1999;ABRUZZESE et al, 2018).…”