Negative effects of bisphenol A on testicular functions in albino rats and their abolitions with Tribulus terristeris L

ABSTRACT This study was conducted to find out the ameliorative properties of Tribulus terristeris L (TT) on BPA induced spermatotoxicity in male albino rats. Mature male albino rats were divided into five groups, Group A was taken as control for comparison group, whereas the other four groups namely B(vehicle control), C (toxic), D (preventive control) and Group E (amelioration group) received distilled water, olive oil, BPA, TT, and (TT + BPA) respectively. Macroscopic results revealed decreased body weight of rats, weight of testes, and the relative tissue weight index (RTWI) in BPA induced group. Hormonal (testosterone) assay results revealed the decreased values of BPA treated group. Microscopic examination of testis of BPA treated rats showed reduction in leydig cells, decreased diameter of seminiferous tubules and low values of Johnsen's scoring. Histological examination showed discontinuity and irregularity of basement membrane and sloughing of the germinal cell linage. Group E showed the body weights of rats, weight of testes, RTWI, and increased, while reduced level of testosterone, reduced number of Leydig cells, decreased diameter of seminiferous tubules and low values of Johnsen's scoring were restored near to normal. These results demonstrate that TT might be beneficial in combating the spermatotoxicity, induced by BPA.

Study on the association between maternal urinary phthalate metabolites and testicular steroid hormones in the cord blood in a Chinese population / 中华预防医学杂志

<p><b>OBJECTIVE</b>The purposes of our study were to investigate the association between maternal urinary phthalate metabolites and the levels of inhibin B (INHB) and insulin-like factor 3 (INSL3) in the cord blood in a Chinese pregnant population.</p><p><b>METHODS</b>Maternal urine samples in the third trimester of pregnancy of 69 participants were collected and stored, and the samples of cord blood (10 ml) were collected at delivery between June 2011 and September 2012 in a comprehensive hospital of gynecology and obstetrics in Tianjin, China.Four phthalate metabolites, monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), and mono-2-ethylhexyl phthalate (MEHP) were measured in the urine samples using liquid chromatography-tandem mass spectrometry. The levels of INHB, INSL3 in the cord blood were tested by ELISA. Associations of phthalate exposure with INHB and INSL3 levels were determined by spearman correlation and multiple regression model analysis.</p><p><b>RESULTS</b>The median concentrations of observed metabolites in descending order were 49.74 µg/L for MMP, 24.96 µg/L for MEHP, 19.52 µg/L for MEP and 17.73 µg/L for MBP. The median concentrations of INHB and INSL3 were 89.09 and 106.21 ng/L.Significant negative associations between INHB and MMP(β' = -0.252), MEP(β' = -0.363) or the sum value (∑PAEs) (β' = -0.346) were found by the multiple regression model analysis. For INSL3, only the sum value (β' = -0.313) was inversely significantly associated with the levels of INSL3 in the cord blood.</p><p><b>CONCLUSIONS</b>Maternal urinary phthalate metabolites were associated with INHB and INSL3 in the cord blood in a Chinese population.</p>

Relação entre os níveis séricos do hormônio anti-Mulleriano, inibina B, estradiol e hormônio folículo estimulante no terceiro dia e o status folicular ovariano / Relationship of serum anti-Müllerian hormone, inhibin B, estradiol and FSH on day 3 with ovarian follicular status

OBJETIVO: examinar a hipótese de que o nível sérico do hormônio anti-Mülleriano (HAM) reflete o status folicular ovariano. MÉTODOS: Desenho: estudo prospectivo. Pacientes: foram incluídas 101 candidatas à FIV-TE submetidas à estimulação ovariana controlada com agonista de GnRH e FSH. Depois de atingir a supressão da hipófise e antes da administração de FSH (dia basal), os níveis séricos de HAM, inibina B e FSH foram avaliados. O número de folículos antrais foi determinado pela ultra-sonografia (dia basal) (folículo antral precoce; 3-10 mm). RESULTADOS: as médias do nível sérico de HAM, inhibina B, E2, P4 e FSH (dia basal) foram 3,4±0,14 ng/mL, 89±4,8 pg/mL, 34±2,7 pg/mL, 0,22±0,23 ng/mL e 6,6±0,1 mUI/mL, respectivamente, e a média do número de folículos antrais precoces foi 17±0,39. O nível sérico do HAM foi negativamente correlacionado com a idade (r= -0,19, p<0,04) e positivamente correlacionado com o número de folículos antrais precoces (r=0,65, p<0,0001), mas isto não se aplicou aos níveis séricos de inibina B, E2 e FSH. CONCLUSÕES: esse dado demonstra a associação do HAM com a quantidade de folículo antral, sendo aquele, portanto, um provável biomarcador do status folicular ovariano.

PURPOSE: to examine the hypothesis that serum anti-Müllerian hormone (AMH) levels reflect the ovarian follicular status. METHODS: Design: prospective study. Patients: we studied 101 IVF-ET candidates undergoing controlled ovarian hyperstimulation with GnRH agonist and FSH. After the achievement of pituitary suppression and before FSH administration (baseline), serum AMH, inhibin B, and FSH levels were measured. The number of antral follicles was determined by ultrasound at baseline (early antral follicles; 3-10 mm). RESULTS: at baseline, median serum levels of AMH, inhibin B, E2, P4 and FSH were 3.42±0.14 ng/mL, 89±4.8 pg/mL, 34±2.7 pg/mL, 0.22±0.23 ng/mL and 6.6±0.1 mIU/mL, respectively, and the mean number of early antral follicles was 17±0.39. Serum levels of AMH were negatively correlated with age (r=-0.19, p<0.04), and positively correlated with number of antral follicles (r=0.65, p<0.0001), but this did not apply to serum levels of either inhibin B, E2 or FSH. CONCLUSION: the data demonstrate an association between AMH and antral follicular counts. Therefore, AMH is probable a biomarker of ovarian follicular status.

Seminal plasma anti-Müllerian hormone level correlates with semen parameters but does not predict success of testicular sperm extraction (TESE) / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To assess seminal plasma anti-Müllerian hormone (AMH) level relationships in fertile and infertile males.</p><p><b>METHODS</b>Eighty-four male cases were studied and divided into four groups: fertile normozoospermia (n = 16), oligoasthenoteratozoospermia (n = 15), obstructive azoospermia (OA) (n = 13) and non-obstructive azoospermia (NOA) (n = 40). Conventional semen analysis was done for all cases. Testicular biopsy was done with histopathology and fresh tissue examination for testicular sperm extraction (TESE) in NOA cases. NOA group was subdivided according to TESE results into unsuccessful TESE (n = 19) and successful TESE (n = 21). Seminal plasma AMH was estimated by enzyme linked immunosorbent assay (ELISA) and serum follicular stimulating hormone (FSH) was estimated in NOA cases only by radioimmunoassay (RIA).</p><p><b>RESULTS</b>Mean seminal AMH was significantly higher in fertile group than in oligoasthenoteratozoospermia with significance (41.5 +/- 10.9 pmol/L vs. 30.5 +/- 10.3 pmol/L, P < 0.05). Seminal AMH was not detected in any OA patients. Seminal AMH was correlated positively with testicular volume (r = 0.329, P = 0.005), sperm count (r = 0.483, P = 0.007), sperm motility percent (r = 0.419, P = 0.021) and negatively with sperm abnormal forms percent (r = -0.413, P = 0.023). Nonsignificant correlation was evident with age (r = -0.155, P = 0.414) and plasma FSH (r = -0.014, P = 0.943). In NOA cases, seminal AMH was detectable in 23/40 cases, 14 of them were successful TESE (57.5%) and was undetectable in 17/40 cases, 10 of them were unsuccessful TESE (58.2%).</p><p><b>CONCLUSION</b>Seminal plasma AMH is an absolute testicular marker being absent in all OA cases. However, seminal AMH has a poor predictability for successful testicular sperm retrieval in NOA cases.</p>

Anti-Müllerian hormone in disorders of sex determination and differentiation

A masculinização dos genitais internos e externos durante o desenvolvimento fetal depende da existência de dois hormônios testiculares distintos: a testosterona secretada pelas células de Leydig conduz à diferenciação dos dutos de Wolff, do seio urogenital e dos genitais externos, enquanto que o hormônio anti-Mülleriano (HAM) produzido pelas células de Sertoli provoca a regressão dos dutos de Müller. A falta de ação do HAM no início da vida fetal resulta na formação de tubas uterinas, útero e terço superior da vagina. Em fetos 46,XY, a falta do HAM pode resultar de disgenesia testicular, afetando tanto as células de Leydig quanto as de Sertoli: nesse caso, a presença de remanescentes Müllerianos está associada a genitais externos femininos ou ambíguos. Por outro lado, distúrbios na ação do HAM podem resultar de mutações em genes que codificam o HAM ou seu receptor: nessa afecção, conhecida como síndrome da Persistência dos Dutos de Müller, a produção de testosterona é normal e os genitais externos são virilizados normalmente. Finalmente, o HAM costuma ser secretado normalmente em pacientes com intersexo decorrente de defeitos restritos à síntese ou à ação de andrógenos, resultando em indivíduos com genitais externos femininos ou ambíguos com ausência de derivados de Müller.

The role of transforming growth factor beta superfamily in male germ cell development / 中华男科学杂志

Transforming growth factor beta (TGF beta) superfamily can regulate the development of primordial germ cell (PGC) and gonocyte. TGF beta, bone morphogenetic protein (BMP), activin, inhibin, and anti-Müllerian hormone (AMH), all of which belong to the TGF beta superfamily, can play important roles in male germ cell development. Their downstream signaling molecules, Smads proteins are involved in the signal transduction pathway. In addition, TGF beta and AMH contribute to the apoptosis during development. Understanding this effect will help to elucidate the molecular mechanism of the early development of male reproductive system and the pathogenesis of testicular cancer.

study on the effect of calcitonin administration on hypophyseal - testicular axis in rats

The present study was designated to clarify the effect of calcitonin [CT] on the hypophysial testicular axis. A total number of forty adult male albino rats were used and they were classified into three main groups. The first group [control group] consisted of 10 adult male albino rats, which were injected intramuscularly with saline allover the period of experiment. The second group: [sCT-, administered group] consisted of 10 adult male albino rats, which were injected with sCT intramuscularly on alternative days, in a dose of 10 U/kg body weight/days for 4 weeks at 10 AM. However the third group [orchidectomized group consisted of 20 adult male rats. This third group was subdivided into two equal groups: Orchidectomized control group which was injected intramuscularly with saline, two weeks after the operation, for four weeks and Orchidectomized CT-administered group which were injected intramuscularly with sCT, two weeks after the operation, on alternative days in a dose of 10 U/kg body weight day for 4 week at 10 AM. The plasma levels of FSH, LH and testosterone were estimated [by radioimmunoassay] and the Ca[2+] plasma levels were estimated [by Clorometric method] for all groups. Also, histopathological examination was performed for the testes of the first and second groups to evaluate the local effect of CT and also to identify the effect of change in plasma gonadotropin levels on the testes.The results of these investigations showed that, the testosterone plasma levels were significantly decreased in healthy group after sCT administration, the FSH and LH plasma levels were significantly decreased in both healthy and orchidectomized groups after sCT administration and sCT administration caused insignificant change in Ca[2+] plasma levels in both healthy and orchidectomized groups after sCT administration. The histopathological study revealed that sCT administration caused thickening of the basement membrane of the seminiferous tubules in 20% of the total number of rats treated with sCT, thickening of the basement membrane and replacement of the interstitial cells of Leydig by halonosis in 50% of the total number of rats treated with sCT and thickening of the basement membrane, replacement of the interstitial cells of Leydig by halonosis and spermatic arrest at the stage of secondary spermatocytes in 30% of the total number of rats treated with sCT. From the above results, it could be concluded that CT administration resulted in a significant reduction in testosterone plasma levels that may be through a reduction in pituitary gonadotropins secretion and through a direct effect on the testes

Anomalías de la diferenciación sexual / Disorders of sex differentiation

In mammals, chromosomal, genetic, gonadal and genital sex are normally coincident. In the XY fetus, the genital ridges express SRY and other genes inducing testicular development. The testes secrete testosterone, which virilizes internal and external genitalia, and AMH induces the progression of the anlagen of the uterus and fallopian tubes. In the XX fetus, ovaries develop; owing to the absence of testicular hormones, internal and external genitalia follow the female pathway. All disorders impairing gonadal differentiation result in a female phenotype, even if no ovarian tissue is present, whereas all disorders inducing an increased androgen production result in virilization of internal and external genitalia, even if ovaries exist. In XY fetuses, only one of the hormone-dependent pathways (androgen- or AMH-dependent) may be affected. Finally, certain disorders that cannot be explained by hormone dysfunction, result from altered expression or function of morphogenetic factors involved in the early development of genital anlagen of the embryo.

En los mamíferos, los sexos cromosómico, genético, gonadal, genital interno y genital externo son normalmente coincidentes. Cuando la constitución cromosómica es XY, las crestas gonadales expresan el gen SRY y otros genes que inducen su desarrollo en sentido testicular. Los testículos producen testosterona, que favorece la masculinización de los conductos genitales internos y de los genitales externos, y AMH, que provoca la regresión del esbozo del útero y de las trompas de falopio. Si la constitución cromosómica es XX, se forman los ovarios; la falta de hormonas masculinas resulta en el desarrollo del útero y trompas y en una diferenciación femenina de los genitales externos. Cualquier alteración del desarrollo que afecte la formación de las gónadas provocará un desarrollo de los genitales en sentido femenino, aún cuando los ovarios no se formen. Cualquier exceso de andrógenos en un feto XX llevará a una virilización de los genitales externos, aún cuando existan los ovarios. En los individuos XY, es posible que se afecte sólo uno de los ejes (andrógenos o AMH). Finalmente, puede haber malformaciones cuya explicación no esté basada en disfunciones hormonales, sino en alteraciones de factores morfogenéticos involucrados en el desarrollo embrionario temprano de los esbozos de los genitales.

Andropausia: mito o realidad / Andropausia: myth or reality

La presente es una revisión sobre el concepto de andropausia. Se describe la presencia de una serie de síntomas que ocurren con la edad en varones. Algunos autores han asociado a estos síntomas con la disminución de la función testicular evidenciada por la disminución en los niveles de testosterona sérica y han sugerido la implementación de la terapia androgénica de reemplazo. En analogía a la menopausia han acuñado el término andropausia. Estudios más recientes han demostrado que los síntomas aparecen tanto en varones que tienen niveles bajos como normales de testosterona sérica, y que dichos cambios podrían deberse a otros facotres como la disminución de horona del crecimiento, IGF-I, y/o los andrógenos adrenales. Es así que el término andropausia, que etimológicamente no se ajusta a la realidad, no tendría un contexto análogo a lo que acontece con la menopausia. Por ello su uso debería ser descartada.

Diferenciación sexual embrio-fetal: de las móleculas a la anatomía / Fetal sex differentiation: from molecules to anatomy

El sexo del embrión queda determinado en el momento de la fecundación según que el espermatozoide contenga un cromosoma X o un cromosoma Y. Sin embargo, trascurren varias semanas durante la embriogénesis humana sin que existan diferencias evidentes-aún al microscopio- entre un feto de sexo femenino y uno de sexo masculino. A partir de la expresión del gen SRY en los fetos XY, las futuras gónadas inician una serie de eventos caracterizados por expresión de proteínas, que determinan cambios citológicos, histológicos y funcionales característicos de los testículos. Este evento relativamente temprano en el desarrollo del sexo se denomina determinación sexual, dada su importancia determinante en el resto de los eventos que se suceden luego. Los testículos secretan dos hormonas, hormona ani-Mülleriana y testorona, cuya acción provoca la masculinización de los esbozos de los órganos genitales internos y externos, que no mostraban hasta entonces diferencias entre los sexos. El proceso de diferenciación de los genitales se denominan diferenciación sexual fetal. Poco se conoce hasta hoy sobre los mecanismo que inducen a las gónadas a tomar caminos ováricos en el feto XX. Es sabido desde hace tiempo, en cambio, que la falta de las hormonas testiculares resulta en la feminización de los genitales internos y externos, independientemente de la existencia o ausencia de ovarios. El conocimiento de los mecanismos moleculares, celulares y endocrinos involucrados en el desarrollo sexual fetal permiten comprender mejor la patología resultante de sus respectivas alteraciones que generan cuadros clínicos conocidos como ambigüedades sexuales

O enigma da determinaçäo gonadal: o que existe além do cromossomo Y? / The enign of gonadal determination: there are Beyond Y chromosome?

Os autores revisam os vários fatores envolvidos no complexo processo de determinação gonadal, passando pelo já clássico SRY (fator de determinação testicular, no braço curto do cromossomo Y) e ressaltando os principais genes candidatos a participarem desta verdadeira "cascata" de determinação gonadal. Os genes candidatos se avolumam e têm mostrado os vários caminhos por que passa o processo-chave da diferenciação sexual, qual seja, a diferenciação de um testículo ou de um ovário. Genes localizados upstream em relação ao SRY (WT1, SF-1, DAX-1 e SOX9), suas interdependências e a ativação de promotores de outros genes, como o promotor do gene do hormônio anti-mülleriano são abordados neste artigo. Apesar de a lista de genes candidatos ter crescido, ainda restam muitas interrogações e ainda resta muito trabalho a ser desenvolvido para que se esclareça com maior precisão este passo crucial no mecanismo de diferenciação sexual.

Función endocrina testicular en la altura / Function endocrine testicular in the height

Se describen las evidencias que demuestran que la altura, tanto en la exposición aguda como en la permanente, se afecta la función endocrina testicular y como estos cambios pueden explicar los fenómenos de aclimatación y adaptación a la altura. En la exposición aguda a la altura hay una normal producción de testosterona pero su excreción está disminuida lo que condiciona una mayor disponibilidad del andrógeno circulante. El incremento de la testosterona permitiría regular la hiperventilación que se produce durante la exposición aguda a la altura para evitar llevar a una alcalosis prolongada por pérdida de CO2, lo que afectaría la salud. La exposición permanente a la hipoxia se observan en dos situaciones la insuficiencia respiratoria obstructiva crónica y en la vida en las grandes alturas. En IMMC lleva cor-pulmonar hay disminución de la T cuando la PAO2 es menor de 60 mm Hg. En el nativo de altura, a relación a Tsérica E2 es mayor que a nivel del mar, tanto en condiciones basales como post-estimulación (GnRh, hCg). En el mal de montaña agudo no se observa el incremento de la testosterona, y la hiperventilación, sin un mecanismo contraregulatorio, conllevaría a una hipocapnea, concomitante con la sintomatología del soroche. En pacientes con mal de montañas crónico hay una disminución de la T. y de la respuesta al hCG, probablemente como consecuencia a la hipoxemia prolongada durante muchos años. El mecanismo que lleve a la hipoxemia y eritrocitos excesiva sería la mayor biodisponibilidad de testosterona que se eleva en la senectud. Esta elevación producirá apnea durante el sueño con hipoventilación e hipercapnea agravando la situación, la caída extrema de la PAO2 o la eritrocitosis excesiva reducían los niveles de T en el MMC, tratando de revertir la situación, lo cual no ocurre, porque probablemente la biodisponibilidad de T en MMC esté también aumentada. El cáncer de próstata es más frecuente en varones procedentes de la altura. Su mayor prevalencia podría deberse a la mayor biodisponibilidad de T por unidad de estradiol en la altura, particularmente en el anciano. En conclusión la T favorece los mecanismos de aclimatación en cambio inhiben los mecanismos de adaptación a la altura. Se sugiere la hipótesis de que los nativos de las grandes alturas no se encuentran adecuadamente adaptados a la altura, lo que explica la presencia de MMC.

The mechanism of low testosterone levels in homozygous sickle-cell disease

Significantly lower testosterone levels are common in male patients with homozygous sickle-cell (SS) disease and have been attributed to either abnormalities of the hypothalamo-pituitary axis or primary testicular failure. The mechanism has now been investigated by observing the response to gonadrotropinthytotropin releasing hormones (GnRH-TRH) in 10 male patients with SS disease and in 10 matched male sibling controls without sickle-cell disease. Mean basal levels of luteninizing hormone (LH) follicular stimulating hormone (FSH) and thyrotropin (TSH) were significantly elevated but prolactin (RL) levels were within the normal range in the SS group. All hormones increased following GnRH-TRH, and proportionate increases over baseline were similar for FSH and TSH in SS and AA subjects, but SS patients showed a lesser percentage increase in LH at 30 minutes, and a higher percentage increase in PRL at 60 minutes. These observations are more consistent with primary testicular failure than with adnormalities of the hypothalmic-pituitaty-testiculat axis.