Puberty arises with testicular alterations and defective AMH expression in rams prenatally exposed to testosterone

Recabarren, Sergio E; Recabarren, Mónica P; Sandoval, Daniel; Carrasco, Albert; Padmanabhan, Vasantha; Rey, Rodolfo; Richter, Hans G.; Marı́n, C.; Sir-Petermann, Teresa; Rojas-García, Pedro

doi:10.1016/j.domaniend.2017.06.004

Cited by 19 publications

(12 citation statements)

References 51 publications

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“…Given previous reports that rams exposed to elevated prenatal androgens exhibit increased testicular mRNA expression of AMH 31 , we investigated whether PNAM mice also manifest an alteration in testicular mRNA expression of AMH and its receptor variants. qPCR was performed to detect mRNA expression of testicular Amh , AMH type 2 receptor ( Amhr2 ) and variants of the AMH type 1 receptor ( Acvr1 , Bmpr1a and Bmpr1b ).…”

Section: Resultsmentioning

confidence: 99%

“…While both genes and environment likely contribute to the familial nature of these features, preclinical studies in the male monkeys 27 and rams 28–30 indicate a detrimental effect of maternal androgen excess on metabolic and reproductive function respectively. Rams exposed to excess prenatal androgens have reduced sperm count, motility and concentration 28–30 and increased testicular mRNA expression of AMH and SOX9 31 in adulthood. These rams also exhibit a disrupted neuroendocrine axis, including significantly elevated FSH 32 , LH and testosterone 33 , and a significantly reduced testosterone to LH ratio in response to GnRH analog administration 32 .…”

Section: Introductionmentioning

confidence: 99%

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The influence of maternal androgen excess on the male reproductive axis

Holland

Prescott

Pankhurst

et al. 2019

Sci Rep

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Prenatal androgen excess is suspected to contribute to the development of polycystic ovary syndrome (PCOS) in women. Evidence from preclinical female animal models links maternal androgen excess with the development of PCOS-like features and associated alterations in the neuronal network regulating the reproductive axis. There is some evidence suggesting that maternal androgen excess leads to similar reproductive axis disruptions in men, despite the critical role that androgens play in normal sexual differentiation. Here, the specific impact of maternal androgen excess on the male hypothalamic-pituitary-gonadal axis was investigated using a prenatal androgenization protocol in mice shown to model PCOS-like features in females. Reproductive phenotyping of prenatally androgenised male (PNAM) mice revealed no discernible impact of maternal androgen excess at any level of the reproductive axis. Luteinising hormone pulse characteristics, daily sperm production, plasma testosterone and anti-Müllerian hormone levels were not different in the male offspring of dams administered dihydrotestosterone (DHT) during late gestation compared to controls. Androgen receptor expression was quantified through the hypothalamus and identified as unchanged. Confocal imaging of gonadotropin-releasing hormone (GnRH) neurons revealed that in contrast with prenatally androgenised female mice, PNAM mice exhibited no differences in the density of putative GABAergic innervation compared to controls. These data indicate that a maternal androgen environment capable of inducing reproductive dysfunction in female offspring has no evident impact on the reproductive axis of male littermates in adulthood.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The influence of maternal androgen excess on the male reproductive axis

Holland

Prescott

Pankhurst

et al. 2019

Sci Rep

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“…Several studies have reported that prenatal exposure to androgens is able to induce polycystic ovaries in rats (Demissie et al 2008, monkeys (Abbott et al 2002) and sheep (Manikkam et al 2006). It has also been reported that prenatal androgen excess can reprogram the expression of genes involved in gonad function in males (Recabarren et al 2017). In addition, fetal programming mediated by prenatal hyperandrogenism is related to hyperinsulinemia, insulin resistance and other metabolic alterations such as cardiovascular disease, dyslipidemia and metabolic syndrome.…”

Section: Introductionmentioning

confidence: 99%

Metformin improves ovarian insulin signaling alterations caused by fetal programming

Heber¹,

Ferreira

Abruzzese³

et al. 2019

Journal of Endocrinology

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Insulin resistance is the decreased ability of insulin to mediate metabolic actions. In the ovary, insulin controls ovulation and oocyte quality. Alterations in ovarian insulin signaling pathway could compromise ovarian physiology. Here, we aimed to investigate the effects of fetal programming on ovarian insulin signaling and evaluate the effect of metformin treatment. Pregnant rats were hyperandrogenized with testosterone and female offspring born to those dams were employed; at adulthood, prenatally hyperandrogenized (PH) offspring presented two phenotypes: irregular ovulatory (PHiov) and anovulatory (PHanov). Half of each group was orally treated with metformin. Metformin treatment improved the estrous cyclicity in both PH groups. Both PH groups showed low mRNA levels ofIr,Irs1andGlut4.Irs2was decreased only in PHanov. Metformin upregulated the mRNA levels of some of the mediators studied. Protein expression of IR, IRS1/2 and GLUT4 was decreased in both PH groups. In PHiov, metformin restored the expression of all the mediators, whereas in PHanov, metformin restored only that of IR and IRS1/2. IRS1 phosphorylation was measured in tyrosine residues, which activates the pathway, and in serine residues, which impairs insulin action. PHiov presented high IRS1 phosphorylation on tyrosine and serine residues, whereas PHanov showed high serine phosphorylation and low tyrosine phosphorylation. Metformin treatment lowered serine phosphorylation only in PHanov rats. Our results suggest that PHanov rats have a defective insulin action, partially restored with metformin. PHiov rats had less severe alterations, and metformin treatment was more effective in this phenotype.

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“…A não diferença quanto às médias de calcificação e seus baixos valores de escore também apontam que não houve situação de degeneração testicular com o passar dos meses (ÜLKER et al, 2005;GOULESTOU, 2017 (CIEŚLAK et al, 2015;NAZARI-ZENOUZ et al, 2016;RECABARREN et al, 2017). Neste caso o tratamento imposto durante a gestação não alterou a testosterona circulante no metabolismo dos animais.…”

Section: Características Do Sêmenunclassified

“…A partir da idade da puberdade à maturidade sexual, parâmetros corporais, testiculares, histológicos, seminais, hormonais, comportamentais e suas associações, têm sido avaliados para classificar capacidade e potencial reprodutivo destes animais (NOTTER et al, 1981;ORGEUR, 1995;ÜLKER et al, 2005;WANG, et al, 2014;BAI et al, 2017;GOULETSOU, 2017;PETRIDIS, et al, 2017;RECABARREN et al, 2017;SCULLY et al, 2018).…”

Section: Introdução Geralunclassified

Ovelhas desafiadas no final da gestação: respostas comportamentais e reprodutivas de cordeiros

Henrique¹

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Puberty arises with testicular alterations and defective AMH expression in rams prenatally exposed to testosterone

Cited by 19 publications

References 51 publications

The influence of maternal androgen excess on the male reproductive axis

The influence of maternal androgen excess on the male reproductive axis

Metformin improves ovarian insulin signaling alterations caused by fetal programming

Ovelhas desafiadas no final da gestação: respostas comportamentais e reprodutivas de cordeiros

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