Neonatal Exposure to Estradiol Valerate Programs Ovarian Sympathetic Innervation and Follicular Development in the Adult Rat1

Sotomayor‐Zárate, Ramón; Dorfman, Mauricio D.; Paredes, Alfonso; Lara, Hernán E.

doi:10.1095/biolreprod.107.063974

Cited by 64 publications

(70 citation statements)

References 43 publications

(71 reference statements)

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“…35 mg oestradiol benzoate used in this study is based on our previous study (Alexanderson et al 2007) since this dose is known to affect insulin sensitivity and metabolism in adult female rats. There is no standardised dose or administration procedure when studying the postnatal effects of oestrogenisation, several different doses and administration regimes have been used (Arai 1964, Pinilla et al 2002, Sotomayor-Zarate et al 2008. However, the injected dose used in our study concurs with other studies where 0 .…”

Section: Discussionsupporting

confidence: 85%

Early postnatal oestradiol exposure causes insulin resistance and signs of inflammation in circulation and skeletal muscle

Alexanderson

Eriksson²,

Stener-Victorin³

et al. 2009

Journal of Endocrinology

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Early postnatal events can predispose to metabolic and endocrine disease in adulthood. In this study, we evaluated the programming effects of a single early postnatal oestradiol injection on insulin sensitivity in adult female rats. We also assessed the expression of genes involved in inflammation and glucose metabolism in skeletal muscle and adipose tissue and analysed circulating inflammation markers as possible mediators of insulin resistance. Neonatal oestradiol exposure reduced insulin sensitivity and increased plasma levels of monocyte chemoattractant protein-1 (MCP-1) and soluble intercellular adhesion molecule-1. In skeletal muscle, oestradiol increased the expression of genes encoding complement component 3 (C3), Mcp-1, retinol binding protein-4 (Rbp4) and transforming growth factor b1 (Tgfb1). C3 and MCP-1 are both related to insulin resistance, and C3, MCP-1 and TGFb1 are also involved in inflammation. Expression of genes encoding glucose transporter-4 (Glut 4), carnitinepalmitoyl transferase 1b (Cpt1b), peroxisome proliferatoractivated receptor d (Ppard) and uncoupling protein 3 (Ucp3), which are connected to glucose uptake, lipid oxidation, and energy uncoupling, was down regulated. Expression of several inflammatory genes in skeletal muscle correlated negatively with whole-body insulin sensitivity. In s.c. inguinal adipose tissue, expression of Tgfb1, Ppard and C3 was decreased, while expression of Rbp4 and Cpt1b was increased. Inguinal adipose tissue weight was increased but adipocyte size was unaltered, suggesting an increased number of adipocytes. We suggest that early neonatal oestrogen exposure may reduce insulin sensitivity by inducing chronic, low-grade systemic and skeletal muscle inflammation and disturbances of glucose and lipid metabolism in skeletal muscle in adulthood.

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Section: Discussionsupporting

confidence: 85%

Early postnatal oestradiol exposure causes insulin resistance and signs of inflammation in circulation and skeletal muscle

Alexanderson

Eriksson²,

Stener-Victorin³

et al. 2009

Journal of Endocrinology

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“…In addition to this role, the incubation of ovaries with NGF enhances the development of primary follicles by increasing the expression of FSHR (Romero et al 2002). The decrease in Ngfb mRNA found in this study could be paralleled with a similar decrease in the NGF peptide, as we previously demonstrated to occur in the adult rat neonatally treated with estradiol valerate, (EV) (Sotomayor-Zarate et al 2008). The small size of the ovary made it impossible to get enough tissue for the EIA to measure NGF.…”

Section: Stress During Gestation Decreases the Follicular Reserve Poolsupporting

confidence: 71%

“…The resulting supernatant was filtered and used for the measurement of NA and 3-methoxy-4-hydroxyphenylglycol (MHPG) using a HPLC system (Sotomayor-Zarate et al 2008, 2011 as previously described.…”

Section: Measurements Of Mrna Levels By Real-time Rt-pcrmentioning

confidence: 99%

Maternal sympathetic stress impairs follicular development and puberty of the offspring

Barra¹,

Cruz²,

Mayerhofer³

et al. 2014

Reproduction

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Chronic cold stress applied to adult rats activates ovarian sympathetic innervation and develops polycystic ovary (PCO) phenotype. The PCO syndrome in humans originates during early development and is expressed before or during puberty, which suggests that the condition derived from in utero exposure to neural-or metabolic-derived insults. We studied the effects of maternal sympathetic stress on the ovarian follicular development and on the onset of puberty of female offspring. Timed pregnant rats were exposed to chronic cold stress (4 8C, 3 h/daily from 1000 to 1300 h) during the entire pregnancy. Neonatal rats exposed to sympathetic stress during gestation had a lower number of primary, primordial, and secondary follicles in the ovary and a lower recruitment of primary and secondary follicles derived from the primordial follicular pool. The expression of the FSH receptor and response of the neonatal ovary to FSH were reduced. A decrease in nerve growth factor (NGF) mRNA was found without change in the low-affinity NGF receptor. The FSH-induced development of secondary follicles was decreased. At puberty, estradiol plasma levels decreased without changes in LH plasma levels. Puberty onset (as shown by the vaginal opening) was delayed. Ovarian norepinephrine (NE) was reduced; there was no change in its metabolite, 3-methoxy-4-hydroxyphenylglycol, in stressed rats and no change in NE turnover. The changes in ovarian NE in prepubertal rats stressed during gestation could represent a lower development of sympathetic nerves as a compensatory response to the chronically increased NE levels during gestation and hence participate in delaying reproductive performance in the rat.

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“…Another possible explanation of our findings concerning greater weight at birth and faster fetal growth is that these characteristics could be related to exposure to elevated hormonal levels in utero, which could also be associated with menopausal age. Animal models have suggested that in utero levels of estrogen and other hormones may play a key role in regulating the development of the ovary (Kezele and Skinner, 2003;Chen et al, 2007;Sotomayor-Zárate et al, 2008). Large size at birth is associated with higher levels of maternal concentrations of estrogen (Troisi et al, 2007).…”

Section: Possible Mechanisms For the Associationmentioning

confidence: 99%

Fetal environment and early age at natural menopause in a British birth cohort study

et al. 2010

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background: Early life development may influence the timing of natural menopause through association with size of the initial follicle pool or early follicular loss. This study examines the relationships of birthweight, gestational age and birthweight standardized by gestational age with early menopause in the 1958 British birth cohort study.methods: Study participants were over 2900 women with data on birthweight, gestational age (obtained at birth), menopausal status at age 44 -45 years and potential confounding factors. Logistic regression was used to study relationships of birthweight, gestational age and birthweight standardized by gestational age with post-menopausal status by 44 -45 years, with and without adjustments for confounding factors.results: There was a U-shaped association between birthweight and menopausal status at 44-45 years: women at either extremes of birthweight (,2.5 and 4.0 kg) had increased odds of post-menopausal status compared with those weighing 3.0-3.49 kg [odds ratio (OR) ¼ 1.91, 95% confidence interval (CI) 1.08, 3.38; 1.81, 95% CI 1.11, 2.97, respectively]. Women with higher birthweight standardized by gestational age (which indicates faster fetal growth rate) also had increased odds of being post-menopausal by 44-45 years (OR for fastest quarter versus second fastest quarter ¼ 1.80; 95% CI 1.16, 2.81). These associations persisted after adjustment for socioeconomic position at birth, adult smoking status and use of oral contraceptives.conclusions: These findings suggest that variations in fetal environment may be associated with the timing of menopause. Given that extremes of birthweight and higher birthweight standardized by gestational age were associated with earlier age at menopause, mechanisms related to these characteristics that also regulate ovarian function should be investigated further.

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Neonatal Exposure to Estradiol Valerate Programs Ovarian Sympathetic Innervation and Follicular Development in the Adult Rat1

Cited by 64 publications

References 43 publications

Early postnatal oestradiol exposure causes insulin resistance and signs of inflammation in circulation and skeletal muscle

Early postnatal oestradiol exposure causes insulin resistance and signs of inflammation in circulation and skeletal muscle

Maternal sympathetic stress impairs follicular development and puberty of the offspring

Fetal environment and early age at natural menopause in a British birth cohort study

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