Perinatal exposure to a low dose of bisphenol-A advances pubertal spermatogenesis of F1 adolescent male rats

2020 ◽  
Author(s):  
Yinyang Bai ◽  
Fang Xiong ◽  
Yun Zhang ◽  
Jie Chen ◽  
Lishuang Xu ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Plasma Levels ◽  
Low Dose ◽  
Male Offspring ◽  
Female Rats ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Perinatal Exposure ◽  
Significant Difference ◽  
The Impact

Abstract Background To investigate the impact of perinatal exposure to a low dose of bisphenol A (BPA) on spermatogenesis in male rats and the underlying mechanism. Methods Female rats were injected subcutaneously with 2 µg BPA/kg/day from gestation day 10 through lactation day 7. The spermatogenesis and expression of key regulatory genes in the testes as well as the central modulators of the hypothalamic-pituitary-gonadal axis were determined in male offspring on postnatal day 18, 21, and 24 (PND18, 21, and 24). Results 1) Perinatal BPA exposure led to an increase in the weight of body and testis in PND21-24 male offspring. The seminiferous tubular diameter and the number of round spermatids were significantly increased in PND21 BPA-rats, while the volumes of the Sertoli cells, spermatogonia and spermatocytes were not significantly altered. 2) Compared to the control rats, the expression levels of key meiotic regulators such as cyclinA1, c-jun and c-fos in the seminiferous tubules were significantly elevated in PND21 BPA-rats. 3) The plasma levels of FSH and LH (PND21 and PND24) as well as the frequency of pulsatile LH secretion (PND21) were significantly increased in BPA-rats, although the plasma levels of testosterone and estrogen showed no significant difference between the two groups. 4) In comparison with control rats, the levels of GnRH mRNA in the preoptic area (POA) and kiss1 mRNA in arcuate nucleus (ARC) were significantly increased in the BPA-rats, whereas the level of ERα mRNA in ARC was decreased, although the number of GnRH-positive cells and ARC kisspeptin-positive cells were unchanged. Interestingly, neither the number of kisspeptin-positive cells nor the level of kiss1 mRNA in the anteroventral periventricular nucleus (AVPV) showed a difference between the two groups. Conclusion Perinatal exposed to a low dose of BPA leads to an increased meiosis of spermatocytes and promotes the spermatogenesis in male offspring, most likely through activation of the hypothalamic-pituitary-gonadal axis.

scholarly journals Vulnerability factors for mephedrone-induced conditioned place preference in rats—the impact of sex differences, social-conditioning and stress

2021 ◽  
Author(s):  
Olga Wronikowska ◽  
Maria Zykubek ◽  
Łukasz Kurach ◽  
Agnieszka Michalak ◽  
Anna Boguszewska-Czubara ◽  
...  
Keyword(s):  
Sex Differences ◽  
Conditioned Place Preference ◽  
Low Dose ◽  
Social Factor ◽  
Place Preference ◽  
Female Rats ◽  
Male Rats ◽  
Social Conditioning ◽  
Male And Female Rats ◽  
The Impact

Abstract Rationale Mephedrone is a frequently overused drug of abuse that belongs to the group of novel psychoactive substances. Although its mechanism of action, as well as toxic and psychoactive effects, has been widely studied, the role of different factors that could contribute to the increased vulnerability to mephedrone abuse is still poorly understood. Objectives The aim of the presented study was to assess the impact of several factors (sex differences, social-conditioning, and chronic mild unpredictable stress — CMUS) on the liability to mephedrone-induced reward in Wistar rats. Methods The rewarding effects of mephedrone in male and female rats were assessed using the conditioned place preference (CPP) procedure. Furthermore, the impact of social factor and stress was evaluated in male rats using social-CPP and CMUS-dependent CPP, respectively. Results Mephedrone induced classic-CPP in female (10 mg/kg), as well as in male (10 and 20 mg/kg) rats. However, the impact of mephedrone treatment during social-CPP was highly dose-dependent as the rewarding effects of low dose of mephedrone (5 mg/kg; non-active in classic-CPP) were potentiated when administered during social-conditioning. Interestingly, social-conditioning with a higher dose of 20 mg/kg (that induced classic-CPP) was able to reverse these effects. Finally, CMUS potentiated rewarding effects of a low dose of mephedrone (5 mg/kg) and increased the level of corticosterone in rats’ prefrontal cortex and hippocampus. Conclusions Altogether, the presented results give new insight into possible factors underlying the vulnerability to mephedrone abuse and can serve as a basis for further studies assessing mechanisms underlying observed effects.

scholarly journals Increase of Anteroventral Periventricular Kisspeptin Neurons and Generation of E2-Induced LH-Surge System in Male Rats Exposed Perinatally to Environmental Dose of Bisphenol-A

Endocrinology ◽  
2011 ◽  
Vol 152 (4) ◽  
pp. 1562-1571 ◽  
Author(s):  
Yinyang Bai ◽  
Fei Chang ◽  
Rong Zhou ◽  
Peng-Peng Jin ◽  
Hirokazu Matsumoto ◽  
...  
Keyword(s):  
Bisphenol A ◽  
G Protein ◽  
Female Rats ◽  
Male Rats ◽  
Perinatal Exposure ◽  
Dependent Manner ◽  
G Protein Coupled Receptor ◽  
Control Male ◽  
Lh Surge ◽  
G Protein Coupled

Abstract Perinatal exposure to environmental levels of bisphenol-A (BPA) impairs sexually dimorphic behaviors in rodents. Kisspeptin neurons in anteroventral periventricular nucleus (AVPV), which plays an important role in the activation of GnRH neurons and the initiation of LH-surge, have been suggested to be sexual dimorphism in rats. This study focused on exploring the influence of a perinatal exposure to an environmental dose of BPA on the development and maturation of male AVPV kisspeptin neurons and hypothalamus-pituitary-gonadal axis. Female rats were injected sc with 2 μg BPA/kg·d from gestation d 10 through lactation d 7. Anatomical and functional changes in AVPV kisspeptin neurons and hypothalamus-pituitary-gonadal axis were examined in prepubertal, pubertal, and adult male rats exposed perinatally to BPA (BPA-rats). Here, we show that in postnatal d (PND)30/50/90 BPA-rats, the number of AVPV kisspeptin-immunoreactive cells was persistently increased in comparison with age-matched control male rats. The number of GnRH-immunoreactive cells in PND30 BPA-rats declined approximately 40% compared with control male rats, whereas that in PND50/90 BPA-rats was increased in a G protein-coupled receptor 54-dependent manner. Estradiol could induce a stable LH-surge in PND90 BPA-rats and control female rats, which was sensitive to the G protein-coupled receptor 54 inhibitor. In PND30/50 BPA-rats, plasma level of LH was higher, but the level of testosterone was lower than control male rats. These findings provide evidence that perinatal exposure to an environmental dose of BPA causes a sustained increase in AVPV kisspeptin neurons in male rats, leading to the generation of estradiol-induced LH-surge system.

Gender difference in arsenic biotransformation is an important metabolic basis for arsenic toxicity

2021 ◽  
Author(s):  
Maihaba Muhetaer ◽  
Mei Yang ◽  
Rongxiang Xia ◽  
Jun Wu
Keyword(s):  
Gender Differences ◽  
Dose Group ◽  
Low Dose ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Arsenic Toxicity ◽  
Male And Female ◽  
Significant Difference ◽  
Medium Dose

Abstract Background: There are gender differences in the biotransformation of arsenic. We investigated the effects of gender differences on arsenic metabolism and arsenic toxicity mechanisms in rat liver tissues. Methods: Rats were treated with different amounts of arsenic compounds. Arsenic form MMA and DMA in the liver was determined by high performance liquid chromatography-hydride generation atomic fluorescence spectroscopy. SAM, ARR, NAD, PNP, PK, and MPO in rat liver were determined by enzyme-linked immunoassay. RT-qPCR was used to determine AS3MT in the liver. Results: Compared with male and female animals in the same group, MMA and DMA were statistically significant in the three groups of iAs3 + high, iAs3 + medium and iAs5+ low (P <0.05). The MMA of male rats in iAs3+ high and medium groups was higher than that of female rats, and the DMA of male rats was lower than that of female rats. As3MT mRNA in the male iAs3+ high group was higher than that of females. Besides, compared between male and female, only in iAS3+ low dose, iAS3+ medium dose, iAS5+ low dose, and iAS5+ medium dose groups, there was significant difference in SAM level (P<0.05). Compared with male and female animals in the same group, male rats had significantly higher PNP and ARR activities while lower PK activity than female rats (P<0.05). Between the male and female groups, only the iAS3+ high dose and medium dose group had a statistically significant difference (P<0.05). The NAD activity of females in iAS3+ high dose group was higher than that of males. Conclusion: Conclusively, under the same arsenic exposure, there were gender differences between female and male rats, and arsenic metabolism was more cytotoxic to male rats than to females.

scholarly journals EPIGENOMIC EFFECTS OF EXPOSURE OF PREGNANT RATS TO LOW DOSE OF BISPHENOL A REGARDING THE NEUROENDOCRINE SYSTEM OF THE MALE F1 GENERATION (short communication)

2021 ◽  
pp. 23-28
Author(s):  
Alexander Reznikov ◽  
Olha Sachynska ◽  
Аnna Lymareva ◽  
Lyubov Polyakova
Keyword(s):  
Sexual Behavior ◽  
Bisphenol A ◽  
Low Dose ◽  
Male Offspring ◽  
Male Rats ◽  
Normal Male ◽  
Potential Hazard ◽  
Preoptic Nucleus ◽  
Female Behavior ◽  
Medial Preoptic Nucleus

Aim: To study the long-term effects of exposure of pregnant Wistar rats to low dose of bisphenol A (BPA) by measuring to the level of steroid hormones and sexual behavior of adult male offspring of the first generation. Material and research methods: BPA as part of the Dorfman gel was gavaged during the last week of pregnancy, when androgen-dependent sexual brain differentiation occurs, in a daily dose of 25 mcg/kg b.w. (threshold teratogenic dose). Male sexual behavior was evaluated by proceptive reactions, the duration of latent and refractory periods, the number of mounts, intromissions and ejaculations in the presence of a receptive female. Female sexual behavior was assessed by lordosis reactions of orchidectomized and activated by the introduction of estradiol and progesterone males in the presence of a normal male. A neuromorphological analysis of the sex-dimorphic area of the brain, the medial preoptic nucleus of the hypothalamus, was performed by histological examination and karyometry of neurons. Results: Prenatally administered BPA caused a very slight increase in the anogenital distance in newborn animals and did not affect the terms of puberty. The levels of testosterone and corticosterone in the blood plasma of males of 6 months of age did not differ from the control indices. At 10 months of age, all experimental males showed sharply weakened sexual motivation for mating with females, and in 4 from 5 animals, copulative components of sexual behavior were absent. There was no ejaculations in the 5th male as well, while numbers of the mounts without intromissions and ones with intromissions significantly reduced. In the BPA group, all descendants showed active female behavior in the presence of a normal male, which manifested in lordosis reactions and a high lordosis index. According to the histological study of medial preoptic nucleus, the activity of neurocytes in the male offspring of BPA-exposed females was significantly reduced, and their nuclei volume distribution was some different from the control. Conclusions: The data obtained indicate epigenetic disorders of the sexual brain differentiation program due to the prenatal exposure to BPA in dose that does not cause significant teratogenic effects. This should be taken into account when evaluating the potential hazard of BPA for reproductive health. Key words: bisphenol A, prenatal effect, male rats, sexual behavior, corticosterone, testosterone.

scholarly journals Perinatal Exposure to Low-Dose Bisphenol A Impairs Spatial Learning and Memory in Male Rats

2013 ◽  
Vol 123 (2) ◽  
pp. 132-139 ◽  
Author(s):  
Rika Kuwahara ◽  
Shinichiro Kawaguchi ◽  
Yumi Kohara ◽  
Haiming Cui ◽  
Kimihiro Yamashita
Keyword(s):  
Bisphenol A ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Low Dose ◽  
Male Rats ◽  
Spatial Learning And Memory ◽  
Perinatal Exposure

Abstract 169: Human Dose tPA Improves Functional Outcomes in Both Sexes in Embolic Model of Stroke: Differential Effect on Hemorrhagic Transformation

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Weiguo Li ◽  
John Paul Valenzuela ◽  
Sally El-Shafey ◽  
Rebecca Ward ◽  
Xinyue Guo ◽  
...  
Keyword(s):  
Infarct Size ◽  
Functional Outcomes ◽  
Low Dose ◽  
Hemorrhagic Transformation ◽  
Female Rats ◽  
Male Rats ◽  
Therapeutic Window ◽  
Human Dose ◽  
Underlying Mechanisms ◽  
The Impact

Tissue plasminogen activator (tPA) is the only FDA-approved therapeutic agent for the treatment of acute ischemic stroke. The widespread use of tPA is still limited by the fear of hemorrhagic transformation (HT) and underlying mechanisms are actively being pursued in preclinical studies. However, experimental models use a 10 times higher dose of tPA than the clinical dose (10 mg/kg) and mostly employ only male animals. In this translational study, we hypothesized that low dose tPA would achieve clot lysis, decrease neurovascular injury and improve functional outcomes in both sexes. Aged-matched male and female Wistar rats (n=5-7) have been treated with or without tPA (1 mg/kg, i.v.) at 90 min after embolic middle cerebral artery occlusion with a fibrin-rich humanized clot. The neurological deficiency (Bederson score and adhesive removal test -ART), infarct size, HT index, and edema ratio were assessed 3 days after surgery (Table). Compared to male rats, female rats had smaller infarct size and better functional outcomes as previously reported in the literature. tPA decreased infarct size in both sexes. tPA reduced edema in males with no effect in females. While there was no difference in HT between males and females without tPA, HT was less in the female + tPA group. Functional outcomes, especially ART, were significantly improved with tPA in both sexes. These data suggest that 1) thrombolysis with a low dose tPA is effective in improving short term outcomes in both sexes, and 2) better functional outcomes in females are further enhanced with tPA. Additional studies are in progress to explore long term effects and the impact of therapeutic window, age and sex steroids on outcomes as well as the underlying mechanisms contributing to less HT in females.

scholarly journals Altered Testicular Histomorphometric and Antioxidant Levels Following In vivo Bisphenol-A Administration

2021 ◽  
Vol 15 (3) ◽  
pp. 165-174
Author(s):  
Eniola Risikat Kadir ◽  
◽  
Lekan Sheriff Ojulari ◽  
Taiye Abdullah Gegele ◽  
Ismail Adetayo Lawal ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Reproductive System ◽  
Low Dose ◽  
Female Rats ◽  
Male Rats ◽  
Melatonin Administration ◽  
Male Wistar Rats ◽  
Environmental Toxin ◽  
Daily Application

Background: Bisphenol-A (BPA) is a pervasive environmental toxin that is used in the production processes of many consumables and equipment that are in daily application. The aim of this study was to determine the effects of BPA on the structural and functional integrity of the reproductive system in male Wistar rats and its interaction with melatonin. Methods: Adult female rats in pro-estrus phases were mated with adult male rats and the conception determined. The male pups were divided into two groups of A and B. These groups were further subdivided into six subgroups each. They were administered varying low doses of BPA (25 or 50mg/kg) and melatonin (10mg/kg) at neonatal and adolescent ages. The testes, epididymis and blood samples were collected for histological, semen and biochemical investigations, respectively. Results: The results show that BPA caused histological alterations, reduced quality and quantity of sperm cells, and induced oxidative stress at birth and adolescence. Conclusion: Bisphenol A exposure, even at low dose, is toxic to the male reproductive system, and melatonin administration did not significantly improve the alterations caused by the BPA.

scholarly journals Behavioral Alterations in Response to Fear-Provoking Stimuli and Tranylcypromine Induced by Perinatal Exposure to Bisphenol A and Nonylphenol in Male Rats

2004 ◽  
Vol 112 (11) ◽  
pp. 1159-1164 ◽  
Author(s):  
Takayuki Negishi ◽  
Katsuyoshi Kawasaki ◽  
Shingo Suzaki ◽  
Haruna Maeda ◽  
Yoshiyuki Ishii ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Male Rats ◽  
Perinatal Exposure ◽  
Behavioral Alterations

Male gender increases sensitivity to renal injury in response to cholesterol loading

2003 ◽  
Vol 284 (4) ◽  
pp. F718-F726 ◽  
Author(s):  
Diana M. Attia ◽  
Roel Goldschmeding ◽  
Mahmoud A. Attia ◽  
Peter Boer ◽  
Hein A. Koomans ◽  
...  
Keyword(s):  
Renal Injury ◽  
Low Dose ◽  
Plasma Cholesterol ◽  
A Priori ◽  
No Synthase ◽  
Male Gender ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Cholesterol Feeding

Males are at greater risk for renal injury than females. This may relate to nitric oxide (NO) availability, because female rats have higher renal endothelial NO synthase (NOS) levels. Previously, our laboratory found susceptibility to proteinuria induced by NOS inhibition in male compared with female rats. Dyslipidemia and hypercholesterolemia dose dependently decreased renal NOS activity and caused renal injury in female rats. We hypothesized that exposure of male rats to hypercholesterolemia would lead to more renal injury in male than in female rats due to an a priori lower renal NO system. Female and male rats were fed no, low-dose, or high-dose cholesterol for 24 wk. Cholesterol feeding dose dependently increased proteinuria in both female and male rats, but male rats developed more proteinuria at similar plasma cholesterol ( P < 0.001). Control males had lower renal NOS activity than control females (4.44 ± 0.18 vs. 7.46 ± 0.37 pmol · min−1 · mg protein−1; P < 0.05), and cholesterol feeding decreased renal NOS activity in males and in females ( P < 0.05). Cholesterol-fed males developed significantly more vascular, glomerular, and tubulointerstitial monocyte/macrophage influx and injury than females. Thus under baseline conditions, male rats have lower renal NOS activity than female rats. This may explain why male rats are more sensitive to renal injury by factors that decrease NO availability, such as hypercholesterolemia.

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