Neonatal androgenization-induced early endocrine–metabolic and ovary misprogramming in the female rat

Ongaro, Luisina; Salvetti, Natalia Raquel; Giovambattista, Andrés; Spinedi, Eduardo; Ortega, Hugo Héctor

doi:10.1016/j.lfs.2015.03.008

Cited by 13 publications

(8 citation statements)

References 34 publications

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“…Administration of testosterone to neonatal females has been classically used as an experimental model to study the mechanisms underlying sex differences in the brain [ 63 ]. This model has also been employed to analyze the long-term effects of increased neonatal androgen levels on the female reproductive axis and the development of polycystic ovary syndrome [ 64 – 67 ] and more recently on metabolic abnormalities [ 67 – 69 ]. Here, we found that testosterone levels remained increased at PND10 in females receiving a single injection of this sex steroid on PND1, but adult levels of testosterone and estradiol were unaffected.…”

Section: Discussionmentioning

confidence: 99%

Age and sex dependent effects of early overnutrition on metabolic parameters and the role of neonatal androgens

et al. 2016

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BackgroundMales and females respond differently to diverse metabolic situations. Being raised in a small litter is reported to cause overnutrition that increases weight gain and predisposes an individual to metabolic disturbances in adulthood; however, existing data are inconsistent. Indeed, significant weight gain and/or metabolic disturbances, such as hyperinsulinemia and hyperleptinemia, are sometimes not encountered. We hypothesized that these inconsistencies could be due to the animal’s sex and/or age at which metabolic parameters are measured.MethodsTo analyze the effects of neonatal overnutrition, male and female Wistar rats were raised in litters of 4 or 12 pups/dam and killed at postnatal days (PND) 10, 21, 30, 50, 85, or 150. In a second study to determine if neonatal sex steroid levels influence sex differences in metabolic parameters, female rats were treated with testosterone on PND1. Effects on weight, length, fat pads, adipokine production, and serum levels of glucose, metabolic hormones, and cytokines were analyzed in both studies.ResultsBy PND10, both males and females raised in small litters had increased body weight, body length, adiposity, and serum glucose, insulin, leptin, and adiponectin levels. Females had a greater increase in inguinal fat, and males had higher expression of leptin messenger RNA (mRNA) and serum insulin, as well as increased testosterone levels. Most of the litter size effects diminished or disappeared after weaning and reappeared during adulthood in males, with sex differences in body size and adiposity being apparent postpubertally. Treatment of females with testosterone on PND1 tended to masculinize some metabolic parameters in adulthood such as increased body weight and serum leptin levels.ConclusionsOur results indicate that (1) both sex and age determine the response to neonatal overnutrition; (2) differences in neonatal sex steroid levels may participate in the development of sex differences in metabolic parameters in adulthood and possibly in the response to neonatal overnutrition; and (3) the comparison of circulating hormone and cytokine levels, even in normal control animals, should take into consideration the early neonatal nutritional environment.

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Section: Discussionmentioning

confidence: 99%

Age and sex dependent effects of early overnutrition on metabolic parameters and the role of neonatal androgens

et al. 2016

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“…Neonatal androgenization by testosterone propionate induced early misprogramming of ovarian functions in the female rats [55]. The obtained results strongly suggested that transient neonatal hyperandrogenemia led to ovarian dysfunctions marked by altered steroidogenesis and folliculogenesis.…”

Section: Eacs With Androgenic and Anti-androgenic Propertiesmentioning

confidence: 72%

Endocrine Active Compounds Actions during Neonatal Period: Effect on the Ovary

Słomczyńska¹,

Grzesiak²,

Stwora³

2018

Selected Topics in Neonatal Care

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Many female reproductive disorders observed during adulthood originate from the neonatal period, which is a critical stage toward the reproductive potency. Human and animal fertility are determined by the pool of primordial follicles that are established during fetal or neonatal life. The earliest stages of follicle development are under control of a variety of factors, including sex steroids. Neonatal period is a "critical developmental window" in which organisms are susceptible to the environmental chemicals that may affect the reproductive health. Endocrine active compounds (EACs) are found abundantly in the environment and interfere with sex steroids (predominantly androgens and estrogens) by either mimicking or blocking their functions. This review covers the current knowledge about the effects of selected EACs with androgenic (testosterone propionate), anti-androgenic (flutamide), estrogenic (diethylstilbestrol, bisphenol A, 4-tert-octylphenol, phtalates and genistein), anti-estrogenic (ICI 182,780 and parabens), or mixed activity (methoxychlor) on the ovary of neonates, focusing on their effects on the early stages of folliculogenesis. These chemicals have been shown to affect oocyte survival, follicle formation, and growth, as well as steroidogenic functions. The better cognition of mechanisms underlying the long-term consequences of the neonatal EACs exposure may in future lead to an understanding of human health risks and developing prevention strategies.

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“…Prenatal exposure to T or DHT also increases estradiol concentrations observed in adult rats [6, 51]. Ongaro and collaborators [52] showed that the TP treatment results in an impaired ovary steroidogenic function with a reduced enzyme gene expression of 17OHP4 [52]. This is possibly caused by a drastic reduction in LH and FSH contents at prepubertal age [53].…”

Section: Discussionmentioning

confidence: 99%

“…The authors found more primary and less antral follicles in the ovaries of juvenile rats (TP-treated), which indicates failure in follicular maturation and, possibly, steroidogenic alterations. This could be explained by the overexpression of the LH receptor related to neonatal androgenization [52]. …”

Section: Discussionmentioning

confidence: 99%

Polycystic ovary syndrome induced by exposure to testosterone propionate and effects of sympathectomy on the persistence of the syndrome

Morales‐Ledesma¹,

Ramos²,

Hernández

2017

Reprod Biol Endocrinol

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BackgroundPolycystic ovary syndrome is a complex disorder affecting 6 to 10% of women of reproductive age. In recent years, the cause of the syndrome has been associated with increased androgen serum levels, as well as sympathetic nervous system hyperactivity. The present study analyzed the effects at birth of a single testosterone propionate dose in rats, as well as the role of the superior ovarian nerve in polycystic ovary syndrome persistence.MethodsNewborn female rats of the CIIZV strain were injected with a single dose of 100 μg testosterone propionate, or corn oil as a vehicle. At 24 days of age, rats were subjected to superior ovarian nerve unilateral or bilateral section. A group of animals was sacrificed on their first vaginal estrus, and a second group was sacrificed at 90 days of age, when they presented an estrus preceded by a proestrus.ResultsTestosterone propionate administration at birth blocked ovulation both in adult animals and in animals sacrificed on the first vaginal estrus. Histological analysis of testosterone propionate-treated adult rat ovaries revealed the development of follicular cysts. Ovulation could not be restored by unilateral or bilateral section, and ovaries presented follicular cyst and absence of corpora lutea.ConclusionsOur results suggest that testosterone propionate treatment at birth results in the development of polycystic ovary syndrome, and that this outcome is not due to superior ovarian nerve noradrenergic innervation hyperactivity.

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Neonatal androgenization-induced early endocrine–metabolic and ovary misprogramming in the female rat

Cited by 13 publications

References 34 publications

Age and sex dependent effects of early overnutrition on metabolic parameters and the role of neonatal androgens

Age and sex dependent effects of early overnutrition on metabolic parameters and the role of neonatal androgens

Endocrine Active Compounds Actions during Neonatal Period: Effect on the Ovary

Polycystic ovary syndrome induced by exposure to testosterone propionate and effects of sympathectomy on the persistence of the syndrome

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