Excess Androgens in Utero Alters Fetal Testis Development

Connolly, Fiona; Rae, Michael T.; Bittner, L.; Hogg, Kirsten; McNeilly, Alan S.; Duncan, W. Colin

doi:10.1210/en.2012-2153

Cited by 21 publications

(20 citation statements)

References 49 publications

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“…In sheep, the highest testosterone concentration was found at approximately 70 days of gestation (FORD; D' OCCHIO, 1989), which is closer to the results found in Bos indicus fetuses. During pregnancy, the increase in androgen concentration is influenced by maternal sources and by the male fetus itself (CONNOLLY et al, 2013).…”

Section: Resultsmentioning

confidence: 99%

Bovine fetal testicular development in the Nellore breed

Souza

Miguel

Maioli

et al. 2017

SCA

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The study of gonadal development improves the understanding of factors that can influence the reproductive development process. This study aims to characterize bovine fetal testicular development and the testosterone level in the Nellore breed. For the study, 162 bovine fetuses aged between 3 and 8 months were collected from Nellore cows at a local abattoir. The fetal age was estimated by DP=8.4+0.087L+5.46√L, where DP is the estimated pregnancy day and L represents fetal length. The fetal gonadal weight (g), width (cm), and thickness (cm) were measured. Thereafter, the gonads were submitted to classic histology processes in 3-µm-thick slices cut at 210 µm intervals. The Sertoli cells, Leydig cells, and germ cells were counted. Blood samples were collected from umbilical cords for testosterone levels. The data were analyzed using the Spearman correlation test followed by Principal Component Analysis and one-way ANOVA to compare the averages between months. The testicular weight and volume were found to have a positive correlation with the numbers of Sertoli cells (r = 0.84; p < 0.0001 and r = 0.92; p < 0.0001, respectively), Leydig cells (r = 0.80; p < 0.0001 and r = 0.90; p < 0.0001, respectively), and germ cells (r = 0.84; p < 0.0001 and r = 0.93; p < 0.0001, respectively) and to be negatively correlated with testosterone plasmatic concentration (r = -0.31; p = 0.0001 and r = -0.22; p = 0.006, respectively) during pregnancy. After the fifth month, the numbers of Sertoli cells, Leydig cells and germ cells differed (p < 0.0001) from the following gestational months. The highest testosterone concentration (p = 0.007) was observed in the fifth month of gestation and was followed by a concentration decrease in the seventh and eighth months. The increase in cell quantity was responsible for the increase in testicular weight and volume during fetal development. On the other hand, the testosterone concentration followed the increase in testicular weight and volume until the 7 th month of gestation and regressed during the 8 th and 9 th months, in addition to the increase in cell number. as mensurações, as gônadas foram submetidas ao processamento histológico clássico, sendo utilizadas para elaboração das lâminas cortes com 3 µm de espessura com intervalos entre cortes de 210 µm. As células de Sertoli, Leydig e germinativas foram contadas. Amostras de sangue foram coletadas do cordão umbilical para quantificação dos níveis de testosterona. Os dados foram analisados utilizando a correlação de Spearman seguida pela análise de componentes principais, sendo o comparativo de médias entre os meses realizados utilizando o one-way ANOVA. O peso e o volume testicular apresentaram correlação positiva com o número de células de Sertoli (r = 0,84; p < 0,0001 e r = 0,92; p < 0,0001, respectivamente), células de Leydig (r = 0,80; p < 0,0001 e r = 0,90; p < 0,0001, respectivamente), e células germinativas (r = 0,84; p < 0.0001 e r = 0,93; p < 0,0001, respectivamente), porém foram negativamente correlacionados com a concentraç...

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Section: Resultsmentioning

confidence: 99%

Bovine fetal testicular development in the Nellore breed

Souza

Miguel

Maioli

et al. 2017

SCA

View full text Add to dashboard Cite

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“…Testosterone and estradiol were measured in extracted serum using an in-house radioimmunoassay (RIA) as previously described [ 22 , 24 ]. For testosterone a primary antibody (rabbit anti-testosterone, AMS Biotechnology, Oxfordshire, UK) and radio-labelled testosterone (AMS Biotechnology) were used while estradiol utilised an in house antibody (ASRM32) and in house estradiol tracer conjugated to HRP.…”

Section: Methodsmentioning

confidence: 99%

In an Ovine Model of Polycystic Ovary Syndrome (PCOS) Prenatal Androgens Suppress Female Fetal Renal Gluconeogenesis

et al. 2015

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Increased maternal androgen exposure during pregnancy programmes a polycystic ovary syndrome (PCOS)-like condition, with metabolic dysfunction, in adult female offspring. Other in utero exposures associated with the development of insulin resistance, such as intrauterine growth restriction and exposure to prenatal glucocorticoids, are associated with altered fetal gluconeogenesis. We therefore aimed to assess the effect of maternal androgenisation on the expression of PEPCK and G6PC in the ovine fetus. Pregnant Scottish Greyface sheep were treated with twice weekly testosterone propionate (TP; 100mg) or vehicle control from day 62 to day102 of gestation. At day 90 and day 112 fetal plasma and liver and kidney tissue was collected for analysis. PEPCK and G6PC expression were analysed by quantitative RT-PCR, immunohistochemistry and western blotting. PEPCK and G6PC were localised to fetal hepatocytes but maternal androgens had no effect on female or male fetuses. PEPCK and G6PC were also localised to the renal tubules and renal PEPCK (P<0.01) and G6PC (P = 0.057) were lower in females after prenatal androgenisation with no change in male fetuses. These tissue and sex specific observations could not be explained by alterations in fetal insulin or cortisol. The sexual dimorphism may be related to the increase in circulating estrogen (P<0.01) and testosterone (P<0.001) in females but not males. The tissue specific effects may be related to the increased expression of ESR1 (P<0.01) and AR (P<0.05) in the kidney when compared to the fetal liver. After discontinuation of maternal androgenisation female fetal kidney PEPCK expression normalised. These data further highlight the fetal and sexual dimorphic effects of maternal androgenisation, an antecedent to adult disease and the plasticity of fetal development.

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“…Complimentary DNA (cDNA) was synthesised from 200 ng RNA in accordance with manufacturer’s protocol (Applied Biosystems, California, USA). Subsequently, qRT-PCR was performed using SYBR Green as previously described [25] . Primer3 Input version 0.4, online software, was used to design forward and reverse primers ( Table 2 ) from DNA sequences obtained from Ensembl Genome Browser, sequences were checked for specificity using Basic Local Alignment Search Tool and validity confirmed as previously described [26] .…”

Section: Methodsmentioning

confidence: 99%

The Local Effects of Ovarian Diathermy in an Ovine Model of Polycystic Ovary Syndrome

et al. 2014

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In order to develop a medical alternative to surgical ovarian diathermy (OD) in polycystic ovary syndrome (PCOS) more mechanistic information is required about OD. We therefore studied the cellular, molecular and vascular effects of diathermy on the ovary using an established ovine model of PCOS. Pregnant sheep were treated twice weekly with testosterone propionate (100 mg) from day 30–100 gestation. Their female offspring (n = 12) were studied during their second breeding season when the PCOS-like phenotype, with anovulation, is fully manifest. In one group (n = 4) one ovary underwent diathermy and it was collected and compared to the contralateral ovary after 24 hours. In another group a treatment PCOS cohort underwent diathermy (n = 4) and the ovaries were collected and compared to the control PCOS cohort (n = 4) after 5 weeks. Ovarian vascular indices were measured using contrast-enhanced ultrasound and colour Doppler before, immediately after, 24 hours and five weeks after diathermy. Antral follicles were assessed by immunohistochemistry and ovarian stromal gene expression by quantitative RT-PCR 24 hours and 5 weeks after diathermy. Diathermy increased follicular atresia (P<0.05) and reduced antral follicle numbers after 5 weeks (P<0.05). There was an increase in stromal CCL2 expression 24 hours after diathermy (P<0.01) but no alteration in inflammatory indices at 5 weeks. Immediately after diathermy there was increased microbubble transit time in the ovarian microvasculature (P = 0.05) but this was not seen at 24 hours. However 24 hours after diathermy there was a reduction in the stromal Doppler blood flow signal (P<0.05) and an increased ovarian resistance index (P<0.05) both of which persisted at 5 weeks (P<0.01; P<0.05). In the ovine model of PCOS, OD causes a sustained reduction in ovarian stromal blood flow with an increased ovarian artery resistance index associated with atresia of antral follicles.

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Excess Androgens in Utero Alters Fetal Testis Development

Cited by 21 publications

References 49 publications

Bovine fetal testicular development in the Nellore breed

Bovine fetal testicular development in the Nellore breed

In an Ovine Model of Polycystic Ovary Syndrome (PCOS) Prenatal Androgens Suppress Female Fetal Renal Gluconeogenesis

The Local Effects of Ovarian Diathermy in an Ovine Model of Polycystic Ovary Syndrome

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