Neuroendocrine and behavioral effects of maternal exposure to oral bisphenol A in female mice

Bisphenol A (BPA) is a widespread estrogenic compound. We investigated the effects of maternal exposure to BPA at reference doses on sexual behavior and neuroendocrine functions of female offspring in C57BL/6J mice. The dams were orally exposed to vehicle alone or vehicle-containing BPA at doses equivalent to the no observed adverse effect level (5 mg/kg body weight per day) and tolerable daily intake (TDI, 0.05 mg/kg body weight per day) level from gestational day 15 until weaning. Developmental exposure to BPA increased the lordosis quotient in naive females exposed to BPA at the TDI dose only. BPA exposure had no effect on olfactory preference, ability to express masculine behaviors or number of calbindin-positive cells, a sexually dimorphic population of the preoptic area. BPA at both doses selectively increased kisspeptin cell number in the preoptic periventricular nucleus of the rostral periventricular area of the third ventricle in adult females. It did not affect the number of GNRH-positive cells or percentage of kisspeptin appositions on GNRH neurons in the preoptic area. These changes were associated with higher levels of estradiol (E2) at the TDI dose while levels of LH, estrus cyclicity, ovarian and uterine weights, and fertility remained unaffected. Delay in the time of vaginal opening was observed during the postnatal period at TDI dose, without any alteration in body growth. This shows that developmental exposure to BPA at reference doses did not masculinize and defeminize the neural circuitry underlying sexual behavior in female mice. The TDI dose specifically exacerbated responses normally induced by ovarian E2, through estrogen receptor α, during the postnatal/prepubertal period.

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Effects of Bisphenol-A (BPA) and black seed oil on body weight, lipid profile and serum glucose in male and female mice

10.33109/bjvmjj19lam2 ◽

2019 ◽

Vol 17 (1) ◽

Author(s):

K. M. Sujan ◽

E. Haque ◽

M. S. Rakib ◽

M. I. Haque ◽

A. Mustari ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Bisphenol A ◽

Lipid Profile ◽

Seed Oil ◽

Serum Glucose ◽

Male And Female ◽

Female Mice ◽

Black Seed ◽

Black Seed Oil

Background: Bisphenol-A [BPA, 2, 2-bis (hydroxyphenyl) propane] is widely used in the manufacture of polycarbonate plastic, water bottles, feeders , baby bottles, epoxy resins and inside coating in metallic food cans. Black seed oil (BSO) (Nigella sativa) commonly known as black cumin, reported to be beneficial in function of various systems in the body. The study was carried out to investigate the effect of BPA and BSO on body weight, lipid profile and serum glucose in male and female mice. Methods : A total of thirty (15 male and 15 female) Swiss Albino mice (Mus musculus), aged 25-28 days with an average body weight of 27.4±1g were randomly divided into 3 groups consisting 5 mice in each for each sex. Group A served as vehicle control. Group B was administered BPA @ 50 mg/kg bw daily, while group C received both BPA @ 50 mg/kg/day and BSO @ 1ml/kg/day respectively. Results: Data revealed that BPA treated mice showed slight increase in body weight gain while BSO controlled the weight gain in BPA treated mice. Cholesterol and LDL values were significantly (p<0.01) increased and Triglycerides value was significantly (p<0.01) decreased in BPA-treated mice without significant alterations in HDL value. BPA & BSO treated female mice showed significant (p<0.01) decreased in cholesterol, triglycerides and LDL values. BPA reduced the blood glucose level and addition of BSO had synergistic effects of glucose utilization. Conclusions: It can be concluded that BPA is one of the potential risk factors for hyperlipidemia and obesity. These harmful effects could be alleviated by the ingestion of black seed oil.

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Vulnerability of the Neural Circuitry Underlying Sexual Behavior to Chronic Adult Exposure to Oral Bisphenol A in Male Mice

Endocrinology ◽

10.1210/en.2013-1639 ◽

2014 ◽

Vol 155 (2) ◽

pp. 502-512 ◽

Cited By ~ 27

Author(s):

Marie Picot ◽

Lydie Naulé ◽

Clarisse Marie-Luce ◽

Mariangela Martini ◽

Kalina Raskin ◽

...

Keyword(s):

Adverse Effect ◽

Body Weight ◽

Sexual Behavior ◽

Androgen Receptor ◽

Bisphenol A ◽

Neural Circuitry ◽

Male Sexual Behavior ◽

Adverse Effect Level ◽

Effect Level ◽

Adult Exposure

There are human reproduction concerns associated with extensive use of bisphenol A (BPA)-containing plastic and, in particular, the leaching of BPA into food and beverages. In this context, it remains unclear whether and how exposure to BPA interferes with the developmental organization and adult activation of male sexual behavior by testosterone. We evaluated the developmental and adult exposure to oral BPA at doses equivalent to the no-observed-adverse-effect-level (5 mg/kg body weight per day) and tolerable daily intake (TDI) (50 μg/kg body weight per day) on mouse sexual behavior and the potential mechanisms underlying BPA effects. Adult exposure to BPA reduced sexual motivation and performance at TDI dose only. Exposed males took longer to initiate mating and reach ejaculation despite normal olfactory chemoinvestigation. This deficiency was not restored by sexual experience and was associated with unchanged circulating levels of testosterone. By contrast, developmental exposure to BPA at TDI or no-observed-adverse-effect-level dose did not reduce sexual behavior or alter the neuroanatomical organization of the preoptic area. Disrupting the neural androgen receptor resulted in behavioral and neuroanatomical effects similar to those induced by adult exposure to TDI dose. Moreover, adult exposure of mutant males to BPA at TDI dose did not trigger additional alteration of sexual behavior, suggesting that BPA and neural androgen receptor mutation share a common mechanism of action. This shows, for the first time, that the neural circuitry underlying male sexual behavior is vulnerable to chronic adult exposure to low dose of BPA and suggests that BPA could act in vivo as an antiandrogenic compound.

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Effects of chronic exposure to bisphenol A in adult female mice on social behavior, vasopressin system, and estrogen membrane receptor (GPER1)

European Journal of Histochemistry ◽

10.4081/ejh.2021.3272 ◽

2021 ◽

Vol 65 (s1) ◽

Author(s):

Brigitta Bonaldo ◽

Antonino Casile ◽

Martina Bettarelli ◽

Stefano Gotti ◽

GianCarlo Panzica ◽

...

Keyword(s):

Body Weight ◽

Social Behavior ◽

Bisphenol A ◽

Adult Female ◽

Chronic Exposure ◽

Corn Oil ◽

Chemical Exposure ◽

Hormonal Changes ◽

Critical Periods ◽

Female Mice

Bisphenol A (BPA), an organic synthetic compound found in some plastics and epoxy resins, is classified as an endocrine disrupting chemical. Exposure to BPA is especially dangerous if it occurs during specific “critical periods” of life, when organisms are more sensitive to hormonal changes (i.e., intrauterine, perinatal, juvenile or puberty periods). In this study, we focused on the effects of chronic exposure to BPA in adult female mice starting during pregnancy. Three months old C57BL/6J females were orally exposed to BPA or to vehicle (corn oil). The treatment (4 µg/kg body weight/day) started the day 0 of pregnancy and continued throughout pregnancy, lactation, and lasted for a total of 20 weeks. BPA-treated dams did not show differences in body weight or food intake, but they showed an altered estrous cycle compared to the controls. In order to evidence alterations in social and sociosexual behaviors, we performed the Three-Chamber test for sociability, and analyzed two hypothalamic circuits (well-known targets of endocrine disruption) particularly involved in the control of social behavior: the vasopressin and the oxytocin systems. The test revealed some alterations in the displaying of social behavior: BPA-treated dams have higher locomotor activity compared to the control dams, probably a signal of high level of anxiety. In addition, BPA-treated dams spent more time interacting with no-tester females than with no-tester males. In brain sections, we observed a decrease of vasopressin immunoreactivity (only in the paraventricular and suprachiasmatic nuclei) of BPA-treated females, while we did not find any alteration of the oxytocin system. In parallel, we have also observed, in the same hypothalamic nuclei, a significant reduction of the membrane estrogen receptor GPER1 expression.

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Maternal exposure to bisphenol A during pregnancy interferes ovaries development of F1 female mice

Theriogenology ◽

10.1016/j.theriogenology.2019.09.045 ◽

2020 ◽

Vol 142 ◽

pp. 138-148 ◽

Cited By ~ 3

Author(s):

Yuanyuan Wei ◽

Chao Han ◽

Shuying Li ◽

Yuqing Cui ◽

Yongzhan Bao ◽

...

Keyword(s):

Bisphenol A ◽

Maternal Exposure ◽

Female Mice

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Expression of type one cannabinoid receptor in different subpopulation of kisspeptin neurons and kisspeptin afferents to GnRH neurons in female mice

Brain Structure and Function ◽

10.1007/s00429-021-02339-z ◽

2021 ◽

Author(s):

Tamás Wilheim ◽

Krisztina Nagy ◽

Mahendravarman Mohanraj ◽

Kamil Ziarniak ◽

Masahiko Watanabe ◽

...

Keyword(s):

Cannabinoid Receptor ◽

Third Ventricle ◽

Glutamate Transporter ◽

Neuroendocrine Cells ◽

Receptor Protein ◽

Specific Expression ◽

Female Mice ◽

Gnrh Neurons ◽

Periventricular Area ◽

Cycle Dependent

AbstractThe endocannabinoids have been shown to target the afferents of hypothalamic neurons via cannabinoid 1 receptor (CB1) and thereby to influence their excitability at various physiological and/or pathological processes. Kisspeptin (KP) neurons form afferents of multiple neuroendocrine cells and influence their activity via signaling through a variation of co-expressed classical neurotransmitters and neuropeptides. The differential potency of endocannabinoids to influence the release of classical transmitters or neuropeptides, and the ovarian cycle-dependent functioning of the endocannabinoid signaling in the gonadotropin-releasing hormone (GnRH) neurons initiated us to study whether (a) the different subpopulations of KP neurons express CB1 mRNAs, (b) the expression is influenced by estrogen, and (c) CB1-immunoreactivity is present in the KP afferents to GnRH neurons. The aim of the study was to investigate the site- and cell-specific expression of CB1 in female mice using multiple labeling in situ hybridization and immunofluorescent histochemical techniques. The results support that CB1 mRNAs are expressed by both the GABAergic and glutamatergic subpopulations of KP neurons, the receptor protein is detectable in two-thirds of the KP afferents to GnRH neurons, and the expression of CB1 mRNA shows an estrogen-dependency. The applied estrogen-treatment, known to induce proestrus, reduced the level of CB1 transcripts in the rostral periventricular area of the third ventricle and arcuate nucleus, and differently influenced its co-localization with vesicular GABA transporter or vesicular glutamate transporter-2 in KP neurons. This indicates a gonadal cycle-dependent role of endocannabinoid signaling in the neuronal circuits involving KP neurons.

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Changes Caused by Low Doses of Bisphenol A (BPA) in the Neuro-Chemistry of Nerves Located in the Porcine Heart

Animals ◽

10.3390/ani11030780 ◽

2021 ◽

Vol 11 (3) ◽

pp. 780

Author(s):

Krystyna Makowska ◽

Slawomir Gonkowski

Keyword(s):

Bisphenol A ◽

Endocrine Disruptor ◽

Sympathetic Innervation ◽

Daily Intake ◽

Everyday Objects ◽

Living Organisms ◽

The Impact ◽

Heart Wall ◽

Cholinergic Structures

Bisphenol A (BPA) contained in plastics used in the production of various everyday objects may leach from these items and contaminate food, water and air. As an endocrine disruptor, BPA negatively affects many internal organs and systems. Exposure to BPA also contributes to heart and cardiovascular system dysfunction, but many aspects connected with this activity remain unknown. Therefore, this study aimed to investigate the impact of BPA in a dose of 0.05 mg/kg body weight/day (in many countries such a dose is regarded as a tolerable daily intake–TDI dose of BPA–completely safe for living organisms) on the neurochemical characterization of nerves located in the heart wall using the immunofluorescence technique. The obtained results indicate that BPA (even in such a relatively low dose) increases the number of nerves immunoreactive to neuropeptide Y, substance P and tyrosine hydroxylase (used here as a marker of sympathetic innervation). However, BPA did not change the number of nerves immunoreactive to vesicular acetylcholine transporter (used here as a marker of cholinergic structures). These observations suggest that changes in the heart innervation may be at the root of BPA-induced circulatory disturbances, as well as arrhythmogenic and/or proinflammatory effects of this endocrine disruptor. Moreover, changes in the neurochemical characterization of nerves in the heart wall may be the first sign of exposure to BPA.

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Neuron activity of the ventromedial hypothalamus and the medial preoptic area of the female monkey during sexual behavior

Brain Research ◽

10.1016/0006-8993(88)90115-1 ◽

1988 ◽

Vol 455 (1) ◽

pp. 65-71 ◽

Cited By ~ 33

Author(s):

Shuji Aou ◽

Yutaka Oomura ◽

Hironobu Yoshimatsu

Keyword(s):

Sexual Behavior ◽

Preoptic Area ◽

Medial Preoptic Area ◽

Ventromedial Hypothalamus ◽

Neuron Activity

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Glycyrrhizic acid: the assessment of a no effect level

Human & Experimental Toxicology ◽

10.1191/096032700682694251 ◽

2000 ◽

Vol 19 (8) ◽

pp. 434-439 ◽

Cited By ~ 39

Author(s):

C E M van Gelderen ◽

J A Bijlsma ◽

W van Dokkum ◽

T J F Savelkoull

Keyword(s):

Body Weight ◽

Pilot Study ◽

Glycyrrhizic Acid ◽

Mild Hypertension ◽

Daily Intake ◽

Long Term Effects ◽

Healthy Female ◽

The Usa ◽

Effect Level

Because from earlier experiments in rats and a pilot study in humans a no effect level of glycyrrhizic acid could not be established, a second experiment was performed in healthy volunteers. The experiment was performed in females only, because the effects were most marked in females in the pilot study. Doses of 0, 1, 2 and 4 mg glycyrrhizic acid/kg body weight were administered orally for 8 weeks to 39 healthy female volunteers aged 19-40 years. The experimentlasted 12 weeks including an adaptation and a “wash-out” period.Ano-effectlevel of2 mg/kgis proposed from the results ofthis study, from which an acceptable daily intake (ADI) of 0.2 mg/kg body weight can be extrapolated with a safety factor of 10. This means consumption of 12 mg glycyrrhizic acid/day for a person with a body weight of 60 kg. This would be equal to 6 g licorice a day, assuming that licorice contains 0.2% of glycyrrhizic acid. The proposed ADI is below the limit advised by the Dutch Nutrition Council of 200 mg glycyrrhizic acid/day. This reflects the relatively mild acute toxicity of glycyrrhizic acid, which is also emphasised by the “generally recognised as safe” (GRAS) status of glycyrrhizic acid in the USA in 1983. However, the long-term effects of a mild chronic intoxication (causing, for example, a mild hypertension), although not immediately lethal, justify special attention to the amount of glycyrrhizic acid used daily.

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The Increase in Signaling by Kisspeptin Neurons in the Preoptic Area and Associated Changes in Clock Gene Expression That Trigger the LH Surge in Female Rats Are Dependent on the Facilitatory Action of a Noradrenaline Input

Endocrinology ◽

10.1210/en.2015-1323 ◽

2016 ◽

Vol 157 (1) ◽

pp. 323-335 ◽

Cited By ~ 7

Author(s):

Bruna Kalil ◽

Aline B. Ribeiro ◽

Cristiane M. Leite ◽

Ernane T. Uchôa ◽

Ruither O. Carolino ◽

...

Keyword(s):

Gene Expression ◽

Median Eminence ◽

Preoptic Area ◽

Clock Genes ◽

Third Ventricle ◽

Female Rats ◽

Ovariectomized Rats ◽

Lh Surge ◽

Clock Gene Expression

Abstract In rodents, kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V) of the preoptic area are considered to provide a major stimulatory input to the GnRH neuronal network that is responsible for triggering the preovulatory LH surge. Noradrenaline (NA) is one of the main modulators of GnRH release, and NA fibers are found in close apposition to kisspeptin neurons in the RP3V. Our objective was to interrogate the role of NA signaling in the kisspeptin control of GnRH secretion during the estradiol induced LH surge in ovariectomized rats, using prazosin, an α1-adrenergic receptor antagonist. In control rats, the estradiol-induced LH surge at 17 hours was associated with a significant increase in GnRH and kisspeptin content in the median eminence with the increase in kisspeptin preceding that of GnRH and LH. Prazosin, administered 5 and 3 hours prior to the predicted time of the LH surge truncated the LH surge and abolished the rise in GnRH and kisspeptin in the median eminence. In the preoptic area, prazosin blocked the increases in Kiss1 gene expression and kisspeptin content in association with a disruption in the expression of the clock genes, Per1 and Bmal1. Together these findings demonstrate for the first time that NA modulates kisspeptin synthesis in the RP3V through the activation of α1-adrenergic receptors prior to the initiation of the LH surge and indicate a potential role of α1-adrenergic signaling in the circadian-controlled pathway timing of the preovulatory LH surge.

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