Endocrine disruption and female reproductive health: Implications on cross-talk between endocrine and autocrine/paracrine axes in the ovary

2020 ◽  
Vol 3 ◽  
pp. 2
Author(s):  
Subhasri Biswas ◽  
Urmi Mukherjee ◽  
Sudipta Maitra

Female reproduction is a blend of neuroendocrine, endocrine, and autocrine/paracrine factors that maintain the appropriate ovarian micro-environment. The growing urbanization prompted exposure to a myriad of environmental toxins carrying the ability to interfere with reproductive processes governed by endogenous hormones, making reproductive health a major global concern. These environmental anthropogenic contaminants, popularly termed as endocrine-disrupting chemicals (EDCs), can disrupt the ovarian homeostasis leading to serious perturbations, namely, anovulation, infertility, estrogen deficiency, and premature ovarian failure. Although gonadotropin action, biosynthesis of gonadal steroids vis-à-vis growth factors comprise the essential modulators within the ovary, the redox balance along with inflammatory and cell death response can dramatically influence the framework of ovarian dynamics; however, details of which remain relatively less understood. The present overview provides an update on candidates (endocrines and autocrine/paracrine) of oogenesis, and the potential impact of EDCs on diverse intra-ovarian entities including but not limited to gonadotropin action, steroidogenic potential, expression of growth factors, and modulation of maturational competence. Moreover, the relative importance of free radical-induced stress, inflammation, and elevated cell death (follicular atresia), in the regulation of ovarian functions and how these intricate yet conjoined mechanisms may alter the reproductive performance of a female will be an issue of discussion.

2020 ◽  
Vol 21 (9) ◽  
pp. 3215
Author(s):  
Majorie B. M. van Duursen ◽  
Julie Boberg ◽  
Sofie Christiansen ◽  
Lisa Connolly ◽  
Pauliina Damdimopoulou ◽  
...  

Currently available test methods are not well-suited for the identification of chemicals that disturb hormonal processes involved in female reproductive development and function. This renders women’s reproductive health at increasing risk globally, which, coupled with increasing incidence rates of reproductive disorders, is of great concern. A woman’s reproductive health is largely established during embryonic and fetal development and subsequently matures during puberty. The endocrine system influences development, maturation, and function of the female reproductive system, thereby making appropriate hormone levels imperative for correct functioning of reproductive processes. It is concerning that the effects of human-made chemicals on the endocrine system and female reproductive health are poorly addressed in regulatory chemical safety assessment, partly because adequate test methods are lacking. Our EU-funded project FREIA aims to address this need by increasing understanding of how endocrine disrupting chemicals (EDCs) can impact female reproductive health. We will use this information to provide better test methods that enable fit-for-purpose chemical regulation and then share our knowledge, promote a sustainable society, and improve the reproductive health of women globally.


2016 ◽  
Vol 10 (1) ◽  
pp. 54-75 ◽  
Author(s):  
Aparna Mahakali Zama ◽  
Arpita Bhurke ◽  
Mehmet Uzumcu

Endocrine-disrupting chemicals (EDCs) are increasingly prevalent in the environment and the evidence demonstrates that they affect reproductive health, has been accumulating for the last few decades. In this review of recent literature, we present evidence of the effects of estrogen-mimicking EDCs on female reproductive health especially the ovaries and uteri. As representative EDCs, data from studies with a pharmaceutical estrogen, diethylstilbestrol (DES), an organochlorine pesticide methoxychlor (MXC), a phytoestrogen (genistein), and a chemical used in plastics, bisphenol a (BPA) have been presented. We also discuss the effects of a commonly found plasticizer in the environment, a phthalate (DEHP), even though it is not a typical estrogenic EDC. Collectively, these studies show that exposures during fetal and neonatal periods cause developmental reprogramming leading to adult reproductive disease. Puberty, estrous cyclicity, ovarian follicular development, and uterine functions are all affected by exposure to these EDCs. Evidence that epigenetic modifications are involved in the progression to adult disease is also presented.


2020 ◽  
Vol 32 (7) ◽  
pp. 637
Author(s):  
Amy Winship ◽  
Jacqueline Donoghue ◽  
Brendan J. Houston ◽  
Jacinta H. Martin ◽  
Tessa Lord ◽  
...  

The 2019 meeting of the Society for Reproductive Biology (SRB) provided a platform for the dissemination of new knowledge and innovations to improve reproductive health in humans, enhance animal breeding efficiency and understand the effect of the environment on reproductive processes. The effects of environment and lifestyle on fertility and animal behaviour are emerging as the most important modern issues facing reproductive health. Here, we summarise key highlights from recent work on endocrine-disrupting chemicals and diet- and lifestyle-induced metabolic changes and how these factors affect reproduction. This is particularly important to discuss in the context of potential effects on the reproductive potential that may be imparted to future generations of humans and animals. In addition to key summaries of new work in the male and female reproductive tract and on the health of the placenta, for the first time the SRB meeting included a workshop on endometriosis. This was an important opportunity for researchers, healthcare professionals and patient advocates to unite and provide critical updates on efforts to reduce the effect of this chronic disease and to improve the welfare of the women it affects. These new findings and directions are captured in this review.


Author(s):  
Annia A. Martínez-Peña ◽  
Kendrick Lee ◽  
James J. Petrik ◽  
Daniel B. Hardy ◽  
Alison C. Holloway

Abstract With the legalization of marijuana (Cannabis sativa) and increasing use during pregnancy, it is important to understand its impact on exposed offspring. Specifically, the effects of Δ-9-tetrahydrocannabinol (Δ9-THC), the major psychoactive component of cannabis, on fetal ovarian development and long-term reproductive health are not fully understood. The aim of this study was to assess the effect of prenatal exposure to Δ9-THC on ovarian health in adult rat offspring. At 6 months of age, Δ9-THC-exposed offspring had accelerated folliculogenesis with apparent follicular development arrest, but no persistent effects on circulating steroid levels. Ovaries from Δ9-THC-exposed offspring had reduced blood vessel density in association with decreased expression of the pro-angiogenic factor VEGF and its receptor VEGFR-2, as well as an increase in the anti-angiogenic factor thrombospondin 1 (TSP-1). Collectively, these data suggest that exposure to Δ9-THC during pregnancy alters follicular dynamics during postnatal life, which may have long-lasting detrimental effects on female reproductive health.


Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1047
Author(s):  
Giovanna Di Emidio ◽  
Stefano Falone ◽  
Paolo Giovanni Artini ◽  
Fernanda Amicarelli ◽  
Anna Maria D’Alessandro ◽  
...  

Mitochondria act as hubs of numerous metabolic pathways. Mitochondrial dysfunctions contribute to altering the redox balance and predispose to aging and metabolic alterations. The sirtuin family is composed of seven members and three of them, SIRT3-5, are housed in mitochondria. They catalyze NAD+-dependent deacylation and the ADP-ribosylation of mitochondrial proteins, thereby modulating gene expression and activities of enzymes involved in oxidative metabolism and stress responses. In this context, mitochondrial sirtuins (mtSIRTs) act in synergistic or antagonistic manners to protect from aging and aging-related metabolic abnormalities. In this review, we focus on the role of mtSIRTs in the biological competence of reproductive cells, organs, and embryos. Most studies are focused on SIRT3 in female reproduction, providing evidence that SIRT3 improves the competence of oocytes in humans and animal models. Moreover, SIRT3 protects oocytes, early embryos, and ovaries against stress conditions. The relationship between derangement of SIRT3 signaling and the imbalance of ROS and antioxidant defenses in testes has also been demonstrated. Very little is known about SIRT4 and SIRT5 functions in the reproductive system. The final goal of this work is to understand whether sirtuin-based signaling may be taken into account as potential targets for therapeutic applications in female and male infertility.


2021 ◽  
Vol 22 (11) ◽  
pp. 5692
Author(s):  
Mayra Colardo ◽  
Noemi Martella ◽  
Daniele Pensabene ◽  
Silvia Siteni ◽  
Sabrina Di Bartolomeo ◽  
...  

Neurotrophins constitute a family of growth factors initially characterized as predominant mediators of nervous system development, neuronal survival, regeneration and plasticity. Their biological activity is promoted by the binding of two different types of receptors, leading to the generation of multiple and variegated signaling cascades in the target cells. Increasing evidence indicates that neurotrophins are also emerging as crucial regulators of metabolic processes in both neuronal and non-neuronal cells. In this context, it has been reported that neurotrophins affect redox balance, autophagy, glucose homeostasis and energy expenditure. Additionally, the trophic support provided by these secreted factors may involve the regulation of cholesterol metabolism. In this review, we examine the neurotrophins’ signaling pathways and their effects on metabolism by critically discussing the most up-to-date information. In particular, we gather experimental evidence demonstrating the impact of these growth factors on cholesterol metabolism.


Author(s):  
Hanna Katarina Lilith Johansson ◽  
Camilla Taxvig ◽  
Gustav Peder Mohr Olsen ◽  
Terje Svingen

Abstract Early ovary development is considered to be largely hormone independent, yet there are associations between fetal exposure to endocrine disrupting chemicals and reproductive disorders in women. This can potentially be explained by perturbations to establishment of ovarian endocrine function rather than interference with an already established hormone system. In this study we explore if Hedgehog (HH) signaling, a central pathway for correct ovary development, can be disrupted by exposure to HH-disrupting chemicals, using the antifungal itraconazole as model compound. In the mouse Leydig cell line TM3, used as a proxy for ovarian theca cells, itraconazole exposure had a suppressing effect on genes downstream of HH signaling, such as Gli1. Exposing explanted rat ovaries (gestational day 22 or postnatal day 3) to 30 µM itraconazole for 72 h induced significant suppression of genes in the HH signaling pathway with altered Ihh, Gli1, Ptch1, and Smo expression similar to those previously observed in Ihh/Dhh knock-out mice. Exposing rat dams to 50 mg/kg bw/day in the perinatal period did not induce observable changes in the offspring’s ovaries. Overall, our results suggest that HH signal disruptors may affect ovary development with potential long-term consequences for female reproductive health. However, potent HH inhibitors would likely cause severe teratogenic effects at doses lower than those causing ovarian dysgenesis, so the concern with respect to reproductive disorder is for the presence of HH disruptors at low concentration in combination with other ovary or endocrine disrupting compounds.


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