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Epilepsy is the chronic non-communicable disease of the nervous system most prevalent in the world. Valproic acid (VPA) is one of the most used drugs in the treatment of epilepsy but with various side effects. One of the organs that can be affected is the testis, where it has been seen that men treated with VPA reduce their fertility rates, in addition to causing endocrine disorders by decreasing androgens and gonadotropins. In animal models, it has been shown to reduce the weights of the glands attached to the male reproductive tract, as well as at the testicular level, decreasing sperm concentration and increasing apoptotic cell count. These effects are because VPA increases reactive oxygen species (ROS), causing damage to macromolecules and affecting all cellular processes sensitive to oxide reduction. Throughout testicular development, in utero, it has been seen that the expression of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase, are lower during early embryonic development, as well as vitamin E (VE) is decreased. Therefore, they are not sufficient to reverse the toxic effects of ROS. The objective of this study was to review the use of VPA during pregnancy, its effect on testicular development, and to explore the potential protective role of vitamin E.

La epilepsia es una enfermedad crónica no transmisible que afecta al sistema nervioso más prevalente en el mundo. Dentro de los tratamientos, uno de los fármacos más utilizados es el ácido valproico (AVP), el que ocasiona diversos efectos secundarios. Entre los órganos que se pueden ver afectados se encuentra la gónada masculina, en donde se ha visto que hombres en tratamiento con AVP reducen sus tasas de fecundidad, además de causar trastornos endocrinos disminuyendo andrógenos y gonadotrofinas. En modelos animales, se ha visto que disminuye los pesos de las glándulas anexas al tracto reproductor masculino, como también a nivel testicular, disminuyendo la concentración espermática y aumentando el recuento de células apoptóticas. Estos efectos se deberían a que el AVP aumenta las especies reactivas de oxígeno (ROS), ocasionando daño en macromoléculas, afectando todos los procesos celulares sensibles a óxido reducción. A lo largo del desarrollo testicular, in utero se ha visto que la expresión de enzimas antioxidantes como superóxido dismutasa, catalasa y glutatión peroxidasa, son más bajos durante el desarrollo embrionario temprano, como también la vitamina E (VE) se encuentra disminuida. Por tanto, no resultan suficientes para revertir los efectos tóxicos de las ROS. El objetivo de esta revisión fue asociar el uso de AVP durante la gestación y sus efectos a nivel del desarrollo testicular y describir el potencial rol protector de la VE.

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El ácido valproico (VPA) es un fármaco antiepiléptico teratógenico que, al ser administrado durante etapas tempranas del embarazo, puede producir alteraciones en el desarrollo embriofetal, las que se manifiestan tanto a nivel del sistema nervioso como del testículo. No obstante, se ha reportado que la administración de vitamina E (VE) podría revertir dichas alteraciones. El objetivo del presente estudio fue determinar el efecto protector de la VE a nivel testicular en fetos y ratones púberes expuestos a VPA durante la fase embrionaria de su desarrollo. Se utilizó un total de 30 ratones hembra adultas gestantes (Mus musculus) cepa BALB/c, las cuales se dividieron en 6 grupos. El estudio contempló el análisis de fetos machos a los 17,5 días post-coital (dpc) y machos juveniles a las 6 semanas post-natal. A los grupos 1 y 4 se les administró 0,3 mL de solución fisiológica (grupos control para 17,5 dpc y 6 semanas postnatal, respectivamente). A los grupos 2 y 5 se les suministró la cantidad de 600 mg/kg de VPA (grupos VPA), en tanto que a los grupos 3 y 6 se les aplicó la misma dosis de VPA complementada con 200 UI de VE (grupos VPA+VE). Se describió la histología normal y patológica del compartimento peritubular del testículo. En los grupos VPA se evidenció una degeneración de la pared peritubular, y atrofia de túbulos seminíferos, así como exfoliación de las células germinales. Por el contrario, en los grupos VPA+VE tales signos no fueron observados y la morfología presentó aspecto normal solo con algunas alteraciones focales. Estos resultados corroboran el hecho que la administración de VE contrarresta en parte, los efectos deletéreos que ocasiona el VPA.

SUMMARY: Valproic acid (VPA) is a teratogenic antiepileptic drug that, when administered during the early stages of pregnancy, can produce alterations in embryo-fetal development, which manifest both at the level of the nervous system and the testicle. However, it has been reported that the administration of vitamin E (VE) could reverse these alterations. The study aimed to determine the protective effect of VE at the testicular level in fetuses and pubertal mice exposed to VPA during the embryonic phase of their development. 30 pregnant adult female mice (Mus musculus) BALB/c strain were used, which were divided into 6 groups. The study included the analysis of male fetuses at 17.5 days post-coital (dpc) and juvenile males at 6 weeks post-natal. Groups 1 and 4 were administered 0.3 mL of physiological solution. Groups 2 and 5 were given 600 mg/kg of VPA (VPA groups), while groups 3 and 6 were given the same dose of VPA supplemented with 200 IU of VE (VPA+VE). The normal and pathological histology of the peritubular compartment of the testis was described. In the VPA groups, degeneration of the peritubular wall, and atrophy of the seminiferous tubules, as well as exfoliation of the germ cells, were evident. On the contrary, in the VPA+VE groups such signs were not observed and the morphology presented a normal appearance with only some focal alterations. These results corroborate the fact that the administration of VE partially counteracts the deleterious effects caused by VPA.

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Terephthalic acid (TPA) is a worldwide aromatic compound widely used to manufacture resins and the raw material for the polymerization reaction with ethylene glycol to produce polyethylene terephthalate, known as PET. The use of TPA extends to the synthesis of phthalates, plasticizers used in various industrialized products such as toys and cosmetics. The present study aimed to evaluate the testicular toxicity of terephthalic acid on male mice exposed in utero and during lactation to TPA in different developmental windows. The animals were treated intragastric with TPA at stock dispersal dosages corresponding to 0.0014 g/ml and 0.56 g/ml of TPA in 0.5% v/v carboxymethylcellulose as well as the control dose, composed solely of dispersion of carboxymethylcellulose (0.5% v/v). Four experimental windows were established: group I-treatment in utero, in the fetal period (gestational day-GD 10.5-18.5), with euthanasia at GD 18.5; group II-treatment in utero, in the fetal period (GD 10.5-18.5) and the lactational period (postnatal day (PND-15)), with euthanasia at 15 days; group III-treatment in utero in the fetal period (DG 10.5-18.5) with euthanasia at 70 days (age of sexual maturity, PND 70); group IV-treatment in utero, in the fetal period (GD 10.5-18.5) and the lactational period (PND-15), with euthanasia at 70 days (PND70). The results indicate that TPA changes the reproductive parameters (testicular weight, GI, penis size, and anogenital index) only at the dose of 0.56 g/ml in the fetal period. Data on the volumetric ratio of the testis elements show that the dispersion with the highest concentration of TPA significantly altered the blood vessel/capillary, lymphatic vessel, and connective tissue percentages. Only at the dose of 0.56 g/ml TPA was it effective in decreasing the Leydig and Sertoli cell numbers of the euthanized animals at GD 18.5. In group II, TPA increased the diameter and lumen of seminiferous tubules, which indicates that TPA accelerated the maturation process of Sertoli cells without changing the number and the nuclear volume of these cells. The Sertoli and Leydig cell numbers of the 70-day animals exposed to TPA in the gestational and lactational period were similar to the control. Therefore, the present study is the first in the literature to show that TPA presents a testicular toxicity during fetal (DG18.5) and postnatal life (PND15), without repercussion in adulthood (70 days).

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OBJECTIVE: The objective was to evaluate the influence of different dietary crude protein (CP) levels during the growth phase on reproductive characteristics and reproductive efficiency as well as the body development of adult male Japanese quail. METHODS: Three hundred one-day-old male quails were distributed into five treatments with diets containing different CP levels (18%, 20%, 22%, 24%, and 26%) in a completely randomized design, with six replicates of ten birds each. The CP diets were applied only during the growth phase (1 to 35 days). At 36 days of age, the birds were transferred to 30 laying cages with three males and nine females each, and all birds received the same diet formulated to meet production-phase requirements until 96 days of age. RESULTS: The growth rate of the birds increased linearly (p<0.01) with increasing dietary CP, but the age of maximum growth decreased (p<0.05). At growth maturity, all birds had the same body weight (p>0.05). At 35 days of age, higher weight gain was obtained (p<0.05) with diets containing 22% CP or higher. No effects on feed conversion were observed in this phase. The increase in dietary CP enhanced (p<0.01) nitrogen intake and nitrogen excretion but did not affect (p>0.05) nitrogen retention. Testis size, seminiferous tubular area, number of spermatogonia, and germinal epithelial height at 35 days of age increased linearly (p<0.05) with dietary CP, while the number of Leydig cells decreased (p<0.01). The Sertoli cell number at 60 days of age increased linearly (p<0.01) with dietary CP. Dietary CP levels did not affect cloacal gland size, foam weight, foam protein concentration, semen volume, or flock fertility at 90 days of age. CONCLUSION: Dietary CP concentration affected body and testicular development in male Japanese quails but did not affect reproductive efficiency.

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The Vietnamese pot-bellied pig is a breed with high investigation potential. However, at the reproductive level, its testicular characteristics are still unknown, as well as the different stages of its development. Therefore, the objective of this work is to describe the postnatal testicular development of Vietnamese pot-bellied pigs. In this study, we used pigs grouped into the neonatal stage, animals at zero weeks; prepubertal stage, animals at three and eight weeks; pubertal stage, animals at twelve and sixteen weeks; and postpubertal stage animals at twenty, twenty-four, twenty-eight and thirty-two weeks of age. The neonatal stage is characterized by gonocytes at different migration phases. In the prepubertal stage, gonocytes were differentiated into spermatogonia at 3 weeks of age, and the first spermatocytes were observed at 7 weeks of age. Puberty was determined to start at 12 weeks because seminiferous tubules are found with complete spermatogenesis and the highest peaks in positive cell counting of androgen receptors (AR) and proliferating cell nuclear antigen (PCNA) factor that later decreased and further stabilized in the following weeks. In the postpubertal stage, an increase in seminiferous tubule areas was observed. The number of apoptotic cells ranged from low to null at all ages. Testosterone (T) and gonadotropin levels had two important peaks at 3 and 24 weeks. The seminiferous epithelium cycle was found to have 11 stages according to acrosome development. These characteristics of Vietnamese pot-bellied pig testes, which are different from rat testes and more similar to human testicles, make them a viable model to study human male reproductive biology. The postnatal testicular development of pot-bellied pigs is different from the postnatal testicular development of other breeds. Therefore, due to this difference in size and easy manipulation, the Vietnamese pig is an alternative for investigation compared to other pig breeds.

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Valproic acid (VPA) is a teratogenic antiepileptic, causing alterations in oxidative stress in prenatal development, being altered the development of the male reproductive system. The purpose of this study was to determine the protective effect of vitamin E (VE) on the testicular development in embryos, foetuses and pubertal mice exposed to VPA, VPA+VE and only VE. Sixty pregnant adult female mice were used, to which they were administered 600 mg/kg of VPA (VPA groups), 600 mg/kg of VPA and 200 IU of VE (VPA+VE groups), 200 IU VE (VE groups) and 0.3 ml of 0.9% physiological solution (control groups), showing at 12.5 days post-coital (dpc), 17.5 dpc and 6 weeks postnatal testicular development, and proliferative and apoptotic indices. The groups treated with VPA presented a smaller testicular volume, with greater interstitial space and a delay in the conformation of the testicular cords, shorter lengths and diameters of the germinal epithelium, a smaller number of germline and somatic cells, an increase in cells apoptotic and less proliferation, with significant differences. VE-treated groups behaved similarly to controls. In conclusion, VE reduces the effects caused by VPA throughout testicular development, from embryonic stages, continuing until pubertal stages.

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Stress at the end of sheep gestation can damage the reproductive development of young males. The aim of the present study was to evaluate the effects of LPS administration in the last third of sheep pregnancy on the reproductive parameters of prepubertal rams. Thirty-six pregnant nulliparous ewes (12 ±â€¯2 months old; 45 ±â€¯6 kg) were assigned to two treatments, LPS (E. coli; 0.8 µg kg-1) and control (placebo/saline) administered in late pregnancy (120 days post-conception). The animals gave birth to 17 male lambs (11 LPS; 8 control). Reproductive development of the young rams was analyzed from 5 to 12 months of age. A completely randomized design in double factorial scheme was used. The data were analyzed by analysis of variance. The model included treatment (LPS; control), age as main effects and their interactions, and the animal as a repeated measure. Means were compared by the PDIFF-SAS (Pr > |t|) at P < 0.05. An effect of age was observed for scrotal circumference, testicular consistency, homogeneity of testicular parenchyma, vascularization, semen quantity and quality, and blood testosterone concentration (P < 0.05). LPS increased sperm defects (P < 0.05) but an interaction with age was not observed (P > 0.05) with higher abnormalities only during months 8 and 9 (P < 0.05) and not thereafter. In summary, LPS did not cause long-term damage to testicular morphology analyzed from the onset of puberty to sexual maturity. However, LPS treatment affected sperm morphology during early puberty of the offspring.

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ABSTRACT Objective. Aimed to describe the characteristics of the onset of puberty in males in Colombian hair ram lambs (Ovino de Pelo Colombiano, OPC), and their crosses with Katahdin and Santa Inés sheep in a farm located in Villavicencio, Meta. Materials and methods. 15 lambs of three biotypes: OPC x OPC (OPC), Santa Ines x OPC (SO) and Katahdin X OPC (KO) from four until 12 months old. Ram lambs were grazing and they had supplementation with commercial salt and water ad libitum. Monthly body weight (BW), scrotal circumference (SC), testicular volume (TV) were measured and testosterone level were determined by Elisa test, and ultrasound of the two testicles was performed to determine the presence of the testicular mediastinum, also evaluating the presence and detachment of the urethral prolongation and then electro ejaculation was performed to determine the macroscopic and microscopic characteristics of the semen. Results. Genotype effect was significant for evolution of body BW, SC, TV over time. The SO and KO crosses presented the highest values in BW, whereas OPC lambs maintained a lower value until the end of the assay. At six months old, the three biotypes presented a minimum concentration of 150 million of sperm per ml with 30% of individual progressive motility. Conclusions. In non-seasonal tropical conditions in Colombia (Orinoquia), depending on the variables included, body weight, testicular development, pennis morphology, semen quality, sperm concentration and testosterone levels, it is postulated that around six months of age, the onset of puberty is displayed in the three biotypes.

RESUMEN Objetivo. Describir las características del inicio de la pubertad en corderos machos (Ovino de Pelo Colombiano, OPC) y sus cruces en una granja ubicada en Villavicencio, Meta. Materiales y métodos. Se evaluaron 15 corderos de tres razas: OPC x OPC (OPC), Santa Inés x OPC (SO) y Katahdin X OPC (KO), a partir de los cuatro meses de edad, cinco corderos por cruzamiento, manejados en pastoreo rotacional, con sal mineralizada comercial y agua a voluntad. Mensualmente hasta los doce meses de edad, se evaluó el peso corporal (PC), circunferencia escrotal (CE), volumen testicular (VT), y se determinó la concentración de testosterona en suero mediante la prueba de Elisa, se determinó la presencia del mediastino testicular mediante ecografía y se evalúo el desprendimiento de la prolongación uretral. Finalmente se determinaron las características macroscópicas y microscópicas del eyaculado. Resultados. El efecto racial o de cruzamiento fue significativo para los resultados del PC, CE y VT en el tiempo. Los cruces OPC y KO presentaron los valores más altos en PC, mientras que los corderos OPC mantuvieron un valor menor de PC hasta el final de la investigación. Se realizaron al menos cuatro evaluaciones seminales hasta la presentación de una concentración mínima de 150 millones de espermatozoides por ml con un 30% de motilidad progresiva individual. Conclusiones. En condiciones tropicales no estacionales en Colombia (Orinoquia), para las variables peso corporal, desarrollo testicular, morfología del pene, calidad del semen, concentración de espermatozoides y niveles de testosterona, se postula que alrededor de los seis meses de edad, se presenta el inicio de la pubertad en los tres biotipos.

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O objetivo deste estudo foi caracterizar o desenvolvimento testicular, avaliar a associaçãoexistente entre o perímetro escrotal (PE) e o volume testicular (VOL), e identificar os parâmetrostesticulares na puberdade, em machos da raça guzerá. Foram avaliados 330 machostotalizando 1757 observações realizadas a cada três meses a partir da desmama até os 36meses. Foram feitas as mensurações do PE, comprimento e largura testiculares. O VOL foicalculado seguindo método descrito por Fields et al. Os animais que apresentaram PE ≥ 20 cmforam submetidos à coleta de sêmen utilizando-se estímulo eletro-ejaculatório. Foram consideradosanimais púberes aqueles que apresentaram pelo menos um espermatozoide móvelno ejaculado. A curva de desenvolvimento testicular foi descrita pela função logística, sendoo ponto de inflexão máximo do perímetro escrotal e do volume testicular aos 13,2 meses deidade (18,1 cm) e 23,3 meses de idade (389,4 cm3), respectivamente. A taxa de crescimentomédia do perímetro escrotal e do volume testicular antes e depois do ponto de inflexãoforam respectivamente: 0,58 cm/m, 16,3 cm3/m, 0,29 cm/m, 7,7 cm3/meses de idade. Aidade média na puberdade foi de 19,6 meses, com 250,6 kg de peso, 22,8 cm de perímetroescrotal e 284,7 cm3 do volume testicular. A proporção de machos púberes na faixa etária de12-16 meses foi de 7,4 %; dos 16-20 meses foi 41,23 %; dos 20-24 foi 68 %; dos 24-28 foi91,96 %. Aos 24 meses de idade, 91,96 % dos animais encontravam-se púberes. Foi verificadauma alta correlação positiva entre PE e VOL (r = 0,91; P<0,001). Estes resultados indicamque na raça guzerá o perímetro escrotal estima de forma eficiente o volume escrotal, podendoser usado como uma medida segura para a seleção de jovens reprodutores...

El presente estudio caracterizó el desarrollo testicular, evaluó la asociación existente entre el perímetro escrotal (PE) y el volumen testicular (VOL) e identificó los parámetros testiculares en la pubertad en machos de la raza guzerat. Se evaluaron 330 machos que totalizaron 1757 observaciones realizadas cada tres meses, desde el destete hasta los 36 meses. Serealizaron mediciones del PE, longitud y ancho testiculares. Se calculó el VOL siguiendo el método descrito por Fields et ál. Los animales que presentaron PE ≥ 20 cm fueron sometidos a la recolección de semen utilizando estímulo electroeyaculatorio. Se consideraron púberes los animales que presentaron por lo menos un espermatozoide móvil en el eyaculado. La curva de desarrollo testicular se describió utilizando la función logística, siendo el punto de inflexión máximo del perímetro escrotal y del volumen testicular a los 13,2 meses de edad (18,1 cm) y 23,3 meses de edad (389,4 cm3), respectivamente. La tasa de crecimiento promedio del perímetro escrotal y volumen testicular antes y después del punto de inflexión fueron respectivamente 0,58 cm/m; 16,3 cm3/m; 0,29 cm/m; 7,7 cm3/meses de edad. La edad promedio en la pubertad fue de 19,6 meses, con 250,6 kg de peso, 22,8 cm de perímetro escrotal y 284,7 cm3 de volumen testicular. La proporción de machos púberes en la franja de12-16 meses fue de 7,4 %; de 16-20 meses, 41,23 %; de 20-24, 68 %; de 24-28 fue de 91,96 %.A los 24 meses de edad 91,96 % de los animales se encontraban púberes. Se verificó una altacorrelación positiva entre PE y VOL (r = 0,91; P < 0,001). Estos resultados indican que en la raza guzerat el perímetro escrotal predice de forma eficiente el volumen escrotal, pudiendo ser usado como una medida segura para la selección de jóvenes reproductores...

The objectives of this study were to characterize testicular development, assess the existingassociation between scrotal circumference (SC) and testicular volume (VOL), as well as toidentify testicular parameters in puberty of males of the Guzerat breed. Three hundred thirtymales were evaluated, totaling 1757 observations every three months, from weaning to 36months of age. SC, testicular length and width were measured. VOL was calculated accordingto the method described by Fields et al. Animals with SC ≥ 20 cm were subjected tosemen collection through electro-ejaculation stimulation. Animals with at least one motilesperm in the ejaculate were considered as pubertal. The testicular development curve wasdescribed using the logistic function, where the maximum inflection point of scrotal circumferenceand testicular volume was at 13.2 months (18.1 cm) and 23.3 months (389.4cm3), respectively. The average growth rate of the scrotal perimeter and testicular volume beforeand after the inflection point was 0.58 cm/m, 16.3 cm3/m, 0.29 cm/m, 7.7 cm3/monthsof age, respectively. Average age in puberty was 19.6 months, with 250.6 kg of weight, 22.8cm of scrotal perimeter and 284.7 cm3 of testicular volume. The proportion of pubescentmales at 12-16 months was 7.4 %; 41.23 % at 16-20 months; 68 % at 20-24 months; 91.96 %at 24-28 months. At 24 months of age, 91.96 % of the animals were pubescent. A highpositive correlation was found between SC and VOL (r = 0.91; P<0.001). These resultsindicate that, in the Guzeratel race, scrotal circumference efficiently predicts scrotal volumeand can therefore be used as a reliable measure for selecting young reproducers...

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