Reproductive effects of endosulfan on male offspring of rats exposed during pregnancy and lactation

1999 ◽  
Vol 18 (9) ◽  
pp. 583-589 ◽  
Author(s):  
P R Dalsenter ◽  
E Dallegrave ◽  
J Rb Mello ◽  
A Langeloh ◽  
R T Oliveira ◽  
...  

1 The reproductive effects of endosulfan on the male offspring of rats were examined. Dams were treated orally with 0, 1.5 or 3.0 mg endosulfan/kg from day 15 of pregnancy to postnatal day (PND) 21 of lactation. The male offspring rats were investigated at PND 65 or 140, corresponding to the pubertal and adulthood stage of development. 2 The dose of 3.0 mg endosulfan/kg induced a decrease in maternal body weight during pregnancy, but litter size and mean birth weight were not affected. Similarly, the age at testis descent and preputial separation was not affected on the male offspring. 3 The daily sperm production (6106) was permanently decreased in the highest dose group when investigated at puberty and at adulthood. At the lowest dose, however, the daily sperm production was significantly reduced only at puberty. 4 Histologically, the percentage of seminiferous tubules showing complete spermatogenesis was significantly decreased at puberty. This finding may explain the decrease in daily sperm production observed in the endosulfan-exposed male rats. 5 The results of this study show that low doses of endosulfan have no apparent effect on developmental landmarks or on the weight of reproductive and accessory sex organ. Daily sperm production was the most susceptible endpoint in the male offspring exposed to endosulfan during pregnancy and lactation. To further understand the reproductive effects of endosulfan on male rat offspring, additional reproductive and toxicokinetic studies should be carried out to determine the extent of endosulfan exposure in male rat offspring in utero and during lactation.

1998 ◽  
Vol 17 (7) ◽  
pp. 365-372 ◽  
Author(s):  
A S Faqi ◽  
P R Dalsenter ◽  
H-J Merker ◽  
I Chahoud

1 Pregnant Wistar rats were treated orally with a single dose of 100 mg3,3',4,4'-tetrachlorobiphenyl (PCB 77)/ kg b.w. or 10 mg3,3',4,4',5 pentachlorobiphenyl (PCB 126)/kg b.w. on day 15 of pregnancy. The control rats received peanut oil at the same day. Developmental landmarks were assessed in all offspring rats and reproductive effects of PCB 77 and PCB 126 on male offspring were studied on postnatal day 65 (at puberty) and on postnatal day 140 (at adulthood). 2 The ano-genital distance as well as the ratio anogenital distance to body length was reduced in male pups of the PCB 126 group and the age at vaginal opening was significantly delayed in the female pups. 3 Testis, brain weights and daily sperm production were permanently increased and seminal vesicle weights were decreased in male offspring of the PCB 77 group. In male rats of PCB 126 group, the brain weights were permanently increased and ventral prostate weights permanently reduced. In both PCB groups, however, serum testosterone concentration was reduced only at adulthood. Additionally, the male rats of the PCB 126 group showed alterations in sexual behavior. In these rats the number of mounts with intromissions was significantly increased. 4 The results of this study show that PCB 126 elicits some TCDD-like reproductive effects after in utero exposure, while the reproductive effects of in utero exposure to PCB 77 on male offspring may be attributed to the neonatal hypothyroidism induced by the substance during early fetal development. Further studies using multiple doses and providing thyroid hormone data will be necessary to support this hypothesis.


Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2885
Author(s):  
Dawid Gawliński ◽  
Kinga Gawlińska ◽  
Irena Smaga

In recent years, strong evidence has emerged that exposure to a maternal high-fat diet (HFD) provokes changes in the structure, function, and development of the offspring’s brain and may induce several neurodevelopmental and psychiatric illnesses. The aims of this study were to evaluate the effects of a maternal HFD during pregnancy and lactation on depressive-like behavior and Cnr1 gene expression (encoding the CB1 receptor) in brain structures of rat offspring and to investigate the epigenetic mechanism involved in this gene expression. We found that a maternal HFD during pregnancy and lactation induced a depressive-like phenotype at postnatal days (PNDs) 28 and 63. We found that a maternal HFD decreased the Cnr1 mRNA levels in the prefrontal cortex with the increased levels of miR-212-5p and methylation of CpG islands at the Cnr1 promoter and reduced the level of Cnr1 gene expression in the dorsal striatum with an increased level of miR-154-3p in adolescent male offspring. A contrasting effect of a maternal HFD was observed in the hippocampus, where upregulation of Cnr1 gene expression was accompanied by a decrease of miR-154-3p (at PNDs 28 and 63) and miR-212-5p (at PND 63) expression and methylation of CpG islands at the Cnr1 promoter in male offspring. In summary, we showed that a maternal HFD during pregnancy and lactation triggered several epigenetic mechanisms in the brains of rat offspring, which may be related to long-lasting alterations in the next generation and produce behavioral changes in offspring, including a depressive-like phenotype.


2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Hizb Ullah ◽  
Faizan Ullah ◽  
Owais Rehman ◽  
Sarwat Jahan ◽  
Tayyaba Afsar ◽  
...  

Abstract Background The industrial revolution has resulted in increased synthesis and the introduction of a variety of compounds into the environment and their potentially hazardous effects have been observed in the biota. The present study was aimed to evaluate the potential endocrine-disrupting effects of chronic exposure to the low concentrations of bisphenol S (BPS) in male rats. Methods Weaning male Sprague-Dawley rats (22 days old) were either exposed to water containing 0.1% ethanol for control or different concentrations of BPS (0.5, 5, and 50 μg/L) in drinking water for 48 weeks in the chronic exposure study. After completion of the experimental period, animals were dissected and different parameters (hormone concentrations, histology of testis and epididymis, oxidative stress and level of antioxidant enzymes in the testis, daily sperm production (DSP), and sperm parameters) were determined. Results Results of the present study showed a significant alteration in the gonadosomatic index (GSI) and relative reproductive organ weights. Oxidative stress in the testis was significantly elevated while sperm motility, daily sperm production, and the number of sperm in epididymis were reduced. Plasma testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) concentrations were reduced and estradiol levels were high in the 50 μg/L-exposed group. Histological observations involved a significant reduction in the epithelial height of the testis along with disrupted spermatogenesis, an empty lumen of the seminiferous tubules, and the caput region of the epididymis. Conclusion These results suggest that exposure to 5 and 50 μg/L of BPS for the chronic duration started from an early age can induce structural changes in testicular tissue architecture and endocrine alterations in the male reproductive system which may lead to infertility in males.


2018 ◽  
Vol 49 (1) ◽  
pp. 395-405 ◽  
Author(s):  
Rosiane Aparecida Miranda ◽  
Claudinéia Conationi da Silva Franco ◽  
Carina Previate ◽  
Vander Silva Alves ◽  
Flávio Andrade Francisco ◽  
...  

Background/Aims: Particulate matter (PM) is an important risk factor for immunological system imbalance due to its small size, which can reach more distal regions of the respiratory tract, independently of its chemical composition. Some studies have suggested that PM exposure is associated with an increased incidence of diabetes, especially in industrialized urban regions. However, studies regarding the effects of PM exposure during perinatal life on glucose metabolism are limited. We tested whether exposure to PM from an urban area with poor air quality during pregnancy and lactation could cause short- and long-term dysfunction in rat offspring. Methods: Samples of < 10 µm PM were collected in an urban area of Cotonou, Benin (West Africa), and reconstituted in corn oil. Pregnant Wistar rats received 50 µg PM/day by gavage until the end of lactation. After birth, we analyzed the dams’ biochemical parameters as well as those of their male offspring at 21 and 90 days of age. Results: The results showed that PM exposure did not lead to several consequences in dams; however, the male offspring of both ages presented an increase of approximately 15% in body weight. Although the blood glucose levels remained unchanged, the insulin levels were increased 2.5- and 2-fold in PM exposure groups of both ages, respectively. HOMA-IR and HOMA-β were also increased at both ages. We also demonstrated that the number, islet area and insulin immunodensity of pancreatic islets were significantly increased at both ages from PM exposure. Conclusion: Our data show that chronic PM exposure by the oral route during perinatal life in rats leads to glucose dyshomeostasis in male offspring both in early and later life. Thus, we suggest that an ambience with poor air quality, mainly where traffic is dense, can contribute to an increase in metabolic disease incidence.


2006 ◽  
Vol 18 (4) ◽  
pp. 497 ◽  
Author(s):  
Renata Mazaro ◽  
Teresa Lúcia Lamano-Carvalho

The purpose of the present study was to investigate the long-lasting effects of neonatal handling on reproductive parameters of male rats. Neonatal handling (pups separated from their mothers, kept isolated at environmental temperature for 20 min and submitted to 1 min of tactile stimulation) was applied from post partum Days 1 to 14 (a stress-hyporesponsive period, SHRP) and the animals were killed at puberty (61 days of age). The number of mature spermatids and the daily sperm production were estimated in homogenates from the right testes and cauda epididymidis. Histometric parameters (diameter of seminiferous tubule, germinal epithelium thickness and number of Sertoli cells) were evaluated in paraplast sections of the left testes. The association of the slightly aversive stimuli applied during the SHRP proved to have lasting deleterious effects on male reproduction, causing lower testicular weight and reduced values of seminiferous tubule diameter and germinal epithelium thickness at puberty, which resulted in a 25% reduction in the daily sperm production and in the number of mature spermatids. Similarly, the number of Sertoli cells per tubular cross section was 20% smaller and the weight and number of spermatozoa were reduced more than 40% in the cauda epididymidis of animals handled.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Caroline Serrano-Nascimento ◽  
Rafael Barrera Salgueiro ◽  
Thiago Pantaleão ◽  
Vânia Maria Corrêa da Costa ◽  
Maria Tereza Nunes

2003 ◽  
Vol 22 (4) ◽  
pp. 171-175 ◽  
Author(s):  
Paulo R Dalsenter ◽  
Samanta L deAraújo ◽  
Helena C da Silva de Assis ◽  
Anderson JM Andrade ◽  
Eliane Dallegrave

The possible reproductive adverse effects of the pesticide endosulfan on male offspring rats exposed in utero and during lactation were investigated. Dams were treated orally with 0, 0.5 or 1.5 mg of endosulfan/kg 21 days prior to mating, during the mating, pregnancy and lactation. Maternal and reproductive outcome data and male sexual development landmarks (testis descent and preputial separation) were assessed. Reproductive endpoints of the male offspring were examined at adulthood: sex organ weights, daily sperm production, spermatid number, sperm transit, sperm morphology and testosterone level. No signs of maternal toxicity were detected at the dose levels tested. Sexual development landmarks were also unaffected. Moreover, with the exception of a significant increase in the relative epididymis weight seen in the group treated with the lowest dose, we have not found any statistically significant adverse effect in the reproductive endpoints investigated at adulthood. The results of the present study indicate that pre and post-natal exposure to low doses of endosulfan (0.5 and 1.5 mg/kg) do not induce significant adverse effects in the reproductive system of male offspring Wistar rats at adulthood.


2020 ◽  
Vol 176 (2) ◽  
pp. 297-311
Author(s):  
Leon E Gray ◽  
Johnathan R Furr ◽  
Christy S Lambright ◽  
Nicola Evans ◽  
Phillip C Hartig ◽  
...  

Abstract Multiple molecular initiating events exist that disrupt male sexual differentiation in utero including androgen receptor (AR) antagonism and inhibition of synthesis, and metabolism of fetal testosterone. Disruption of androgen signaling by AR antagonists in utero reduces anogenital distance (AGD) and induces malformations in F1 male rat offspring. We are developing a quantitative network of adverse outcome pathways that includes multiple molecular initiating events and key events linking anti-AR activities to permanent reproductive abnormalities. Here, our objective was to determine how accurately the EC50s for AR antagonism in vitro or ED50s for reduced tissue growth in the Hershberger assay (HA) (key events in the adverse outcome pathway) predict the ED50s for reduced AGD in male rats exposed in utero to AR antagonists. This effort included in-house data and published studies from the last 60 years on AR antagonism in vitro and in vivo effects in the HA and on AGD after in utero exposure. In total, more than 250 studies were selected and included in the analysis with data from about 60 potentially antiandrogenic chemicals. The ability to predict ED50s for key events and adverse developmental effects from the in vitro EC50s displays considerable uncertainty with R2 values for HA and AGD of &lt; 6%. In contrast, there is considerably less uncertainty in extrapolating from the ED50s in the HA to the ED50s for AGD (R2 value of about 85%). In summary, the current results suggest that the key events measured in the HA can be extrapolated with reasonable certainty to predict the ED50s for the adverse in utero effects of antiandrogenic chemicals on male rat offspring.


1995 ◽  
Vol 132 (6) ◽  
pp. 765-770 ◽  
Author(s):  
B Díaz López ◽  
MD Colmenero Urquijo ◽  
ME Díaz Rodriguez ◽  
A Arce Fraguas ◽  
A Esquifino Parras ◽  
...  

Díaz López B, Colmenero Urquijo MD, Díaz Rodriguez ME, Arce Fraguas A, Esquifino Parras A, Marín Fernández B, Effect of pinealectomy and melatonin treatment during pregnancy on the sexual development of the female and male rat offspring. Eur J Endocrinol 1995;132:765–70. ISSN 0804–4643 Sexual development of female and male rat offspring of control, pinealectomized (PIN-X) or melatonin (MEL 2 50 μg/100 g body wt)-treated mother rats during pregnancy was studied. Newborns were studied at the following phases of sexual development: neonate (5 days old), infantile (15 days old), juvenile (25 and 30 days old) and pubertal phase (55 days). In female offspring, MEL treatment during pregnancy significantly increased plasma luteinizing hormone (LH) in 15- and 25-day-old rats; however, at the end of the prepubertal period (30 days) the concentration of plasma LH decreased significantly as compared to control rats. This hormonal pattern was different from that observed in offspring of control and PIN-X rats, which had low LH levels at 25 days of age and higher LH levels at 30 days of age. Follicle-stimulating hormone (FSH) did not vary significantly among the three groups. Plasma prolactin levels were affected by PIN-X of the mother, showing significantly higher levels in the 5-day-old offspring than in the controls; plasma prolactin levels were also affected by MEL treatment of the mother, producing hyperprolactinemia in the 30-day-old female offspring. In male offspring, sexual development in control male rats progressed rapidly with significantly increased LH and FSH levels at 25 and 30 days compared to those measured during the neonatal and infantile periods. Pinealectomy of the mother induced the following modifications: in 5-, 15- and 30-day-old male rats, decreased LH levels were measured relative to the other two groups studied in 5- and 25-day-old rats, significantly lower FSH levels than in the control rats were recorded. However, in 5- and 15-day-old rats, significantly higher prolactin levels than in control rats were measured. Melatonin injections during pregnancy decreased FSH levels at 5, 25, 30 and 55 days as compared to the control males. Also, MEL increased LH levels in 25-day-old rats and significantly decreased prolactin levels in 15- and 55-day-old rats as compared to the other two groups. These results indicate that the mother's pineal gland and MEL treatment can act on fetal development and influence the postnatal ontogeny of the hormones involved in the neuroendocrine–reproductive axis in developing rats. The effect of MEL was apparent during pubertal stages of the offspring, while the effect of PIN-X was more apparent during the juvenile period of the young rats. Beatriz Díaz López, Dpt. Biología Funcional, Arca Fisiología, Fac, Medicina, Universidad de Oviedo, 33006-Oviedo, Spain


2001 ◽  
Vol 20 (8) ◽  
pp. 393-397 ◽  
Author(s):  
K Ben Rhouma ◽  
O Tébourbi ◽  
R Krichah ◽  
M Sakly

The reproductive toxicity of DDT was investigated in adult male rats exposed to 50 and 100 mg/kg body weight (b.wt) day 1 for 10 successive days. Compared with control animals, administration of DDT led to a dose-dependent reduction of testicular weight and the number as well as the percentage of motile spermatozoa in the epididymis. Testicular histological observationsrevealed alsoamarkedloss of gametes in the lumen of seminiferous tubules. In DDT treated rats, the seminal vesicles weights dropped significantly, resulting from a decrease of testosterone production by testes, whereas serum LH and FSH increased after pesticide exposure. This increase of gonadotrophin levels may be related to an impairment of the negative feedback exerted by the steroid on the hypothalamic–pituitary axis. It is concluded that DDT induced adverse effects on male rat fertility by acting directly on the testes and altering the neuroendocrinefunction.


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