Many countries have reported a deterioration in male reproductive health. The levels of serum testosterone, as well as the quality of semen, have been deteriorating . Moreover, congenital cryptorchidism rates, such as testicular germ cell tumors and undescended testis, have increased  The spread of endocrine-disrupting substances in the environment has been proposed to be one cause of these harmful effects in both animals and humans . Because of an unprecedented increase in producing and utilizing agricultural and industrial chemicals in recent years, humans are thought to be regularly and irresponsibly subjected to a broad range of endocrine-disruptive substances .
Bisphenol A (BPA) is now frequently used as the base for polycarbonate plastics, polycarbonate plastics, epoxy resins, as well as a variety of other plastic-based items, including reusable plastic food containers, dental sealants, and baby bottles [5,6].
BPA polymers break down because of heating, aging, heating, and interaction with bases and acids, such as those present in detergents or any cleaning product [7,8]. In a process known as ‘leaching,’ BPA penetrates the contents of different food containers, saliva, as well as dust particles, offering several entry sites for BPA into the physiological systems of humans and animals’ [9,10].
BPA may be ingested, but it can also be inhaled. BPA can move via the bloodstream and into enterohepatic circulation after being absorbed into the lungs, in which it can behave as if consumed orally as well as pass via the digestive system [11,12].
BPA has been associated with many harmful effects on the human health, including impaired development or reproduction, modified metabolism, cancer, and behavioral and neurological issues . BPA is an endocrine-disruptive chemical owing to its anti-thyroid activity, antiandrogenic activity, estrogenic activity, and interaction with hormonal functions .
The testis is a highly sensitive organ to the toxicity induced by BPA . This toxicity is evident by the reduction of testis, body, as well as the weight of epididymis  along with impaired seminiferous tubules  with a decrease of its diameter . Exposure to BPA is deleterious to the reproductive system of males as it triggers oxidative stress in experimental animals . Moreover, it decreases the levels of blood–testis barrier-related proteins in cultivated Sertoli cells , glutathione levels in serum/plasma, glutathione-peroxidase (GSH), superoxide dismutase (SOD), and catalase (CAT) activities [19,21].
High-dose BPA affects animals’ prostate gland, including a reduced lumen, elevated epithelial height, atypical and reactive hyperplasia, as well as the elevated occurrence of prostatic multifocal inflammation [22,23,24]. The interactions between the mesenchyma/stroma and the epithelium, as well as those between the various types of cells in the epithelium, influence the function and development of prostate . The epithelial–mesenchymal transition (EMT), a highly specialized mechanism associated with tumor metastasis and oncogenesis, has been extensively studied for its effects on the loss of adhesion between prostatic epithelial cells. In such processes, epithelial cells inhibit genes producing cell adhesion proteins (e.g. E-cadherin), along with acquiring mesenchymal features such as N-cadherin, vimentin, and developing a flattened phenotype that becomes more migrating. After EMT, the cells may develop into various cell types or return to epithelial cells .
Coenzyme Q10 (CoQ10) is a 1,4-benzoquinone molecule formed in all organs and is abundant in the pancreas, kidney, liver, and heart . It is an element of the chain of electron transport in mitochondria . Meat, seafood, broccoli, and cauliflower all have high levels of CoQ10 . CoQ10 has antioxidative properties because it interacts with singlet oxygen and oxygen-based radicals to prevent lipid peroxidation and bimolecular damage . In impaired testis, CoQ10 improves testicular GSH, SOD, as well as CAT activities while decreasing the levels of malondialdehyde (MDA) [28,31]. Moreover, researchers speculated an antiapoptotic effect of CoQ10 on males’ reproductive systems [31,32]. In addition, it enhanced SOD activities, testicular GSH, serum testosterone , motility and count of sperm, as well as daily production of sperm in substantial toxicity triggered by the magnetic field . The aim of this research was to evaluate the biochemical and pathological alterations of BPA on the structure of the prostate and the ultrastructure of testis of adult male albino rats via immunohistochemical and electron microscopical study and the potential protective effect of CoQ10 supplementation.
Materials and methods
A total of 30 albino male Wistar rats, ranging between 180 and 220 g in weight, were procured from the animal farm in Helwan, Cairo, Egypt. Animals were kept in cages made of stainless steel (three animals per cage) during the whole experiment. They were allowed to acclimate to the laboratory environment for a whole week before the start of experiments in a well-ventilated animal house at standard temperature (22°C 5°C), humidity (50±15%), and photoperiod. Rats were fed a regular dry pellet diet and water ad libitum. This research was carried out in the Faculty of Medicine for Girls at AL-Azhar University in Cairo. It was approved by Research Ethics Committee at Faculty of Medicine for Girls Al-Azhar University, Cairo, Egypt (IRB 2018122001).
BPA [2, 2-bis [4-hydroxyphenyl] propane] (<99% pure) powder was purchased from Sigma-Aldrich (Saint Louis, Missouri, USA). BPA was dissolved in corn oil . CoQ10 was obtained from Arab Company for Pharmaceuticals and Medicinal Plants (MEPACO-MEDIFOOD) Enshas-Sharkeya, Egypt; each capsule had 30 mg of CoQ10 subsequently diluted in 0.4 ml of 0.9 % NaCl .
The rats were categorized into five cohorts (six rats each). Experimental groups were as follows:
- Control group (negative control) was given only distilled water, as well as food.
- Oil group was given corn oil (1 mg/kg).
- CoQ10 group was given 10 mg/kg/day orally, and CoQ10 was dissolved in distilled water .
- Groups II and III were referred to as positive controls.
- BPA group received 200 mg/kg/day, which is equivalent to 0.06 of oral Bisphenol LD50 .
- Q10+bisphenol group received BPA 200 mg/kg/day+Q10 10 mg/kg/day.
Treatment was given orally by an intragastric tube for 30 days. The animals received an overdose of anaesthetic to terminate the experiment within 24 hours of the last dose of treatment with any of the medications employed. Blood samples were taken and then collected in tubes of glass. Serum was separated by being centrifuged for 10 min at 1800g and subsequently stored at −80°C to be preserved for hormonal assay. Prostate, epididymis, and testes were immediately excised and rinsed with isotonic saline to be preserved for light and electron microscopic study. All steps conformed with the guide for the care and use of laboratory animals .
The following parameters were measured:
- Fertility hormones: FSH, LH, and testosterone [MAGLUMI (CLIA) Shenzhen new industries, Biomedical Engineering Co Ltd., UK, London, England] were estimated by a commercially available chemiluminescence immunoassay kit, based on the instructions of the manufacturer.
- Antioxidant assay: MDA was measured in accordance with Sato et al.  and Koracevic et al. , respectively, utilizing the commercially available kits obtained from Cayman Chemical (Ann Arbor, Michigan, USA). Moreover, SOD and CAT were evaluated spectrophotometrically, as described by Claiborne and Sun and colleagues using kits purchased from Biodiagnostics, Giza, Egypt. Samples were processed and assayed according to the manufacturer’s protocol.
Sperm count and morphology
It was based on the technique described by Wyrobek . Both epididymides from each rat were minced with ophthalmic scissors in 5-ml saline (0.9% sodium chloride) and then left for 2 min at least for the spermatozoa to disperse into the saline. This solution was taken by pipetted and then filtered in a test tube to remove large fragments of tissues. The count of epididymal sperm was then estimated by placing a slight drop of suspension on the hemocytometer slide . Sperms were viewed using a high-powered light microscope.
Regarding sperm morphology evaluation, three slides were prepared for each animal by putting a single drop of suspension on a clean microscopic slide. Subsequently, slides were left to dry in the air, submerged in absolute alcohol for 1 min, and then stained with eosin Y (0.4% aqueous) for 15 min. For each animal, ∼1000 sperms were examined for the presence of morphological abnormalities such as amorphous head, banana head, coiled tail, and divided tail.
Sperm viability and motility
After dissection, the cauda epididymis was gently cut with a scissor and soaked in 0.5 ml of phosphate-buffered saline (pH 7.3) that had been prewarmed at 37 °C with a droplet of nigrosin dye. A 50 l aliquot was taken, placed on a glass slide that had been cleaned and warmed (to 37°C), and then inspected under a 40× light microscope. A professional who was unaware of the treatment groups examined the motility of 100 samples of sperm. Every sample was assessed three times, with mean results representing the overall motility of sperm. A droplet of nigrosin and eosin was mixed with the sperm sample to determine viability. A volume of 10 l was deposited on a prewarmed and clean slide made of glass and viewed at 100× magnification using a microscope. A person who was blinded to the groups of treatment examined 10 fields. Eosin staining was detected in 100 sperm/fields, and the quantities of dead and living sperm were assessed. Each sample was repeated three times, with the average quantity given as the percent of viable sperm .
The specimens from the prostate were removed and placed in 10% buffered formalin for 6 h, and specimens from testes were placed in 5% glutaraldehyde solution and then embedded in paraffin blocks, cut at 3–5 μm, prepared for routine hematoxylin as well as eosin (H&E) staining. Alternations in the organizational structure of testes and prostate were viewed utilizing Leica Microscope (New York Microscope Company) with digital cameras (Canon, Japan).
Immunohistochemistry of prostate
The immunohistochemical staining procedure for E-cadherin and vimentin was performed using the streptavidin-biotin immunoperoxidase method (Dako-Cytomation, Glostrup, Denmark). On positively charged slides, tissue sections were cut at a thickness of between 3 and 5 m from the blocks, and the paraffin was removed using xylene before being rehydrated with graduated alcohol. After this, buffered citrate (pH 6.0) was used for heating the sections for 20 min before being rinsed in PBS (pH 7.3). The activity of endogenous peroxidases was blocked utilizing 6% H2O2 in methanol. The immunohistochemical staining for E-cadherin (mouse monoclonal antibody MS-9470-R7, Thermo scientific, USA) and vimentin (Dako, USA; Isotype IgG1 Kappa) was performed. The slides were incubated at room temperature for 2 h with the primary antibody and washed by PBS. Slides were treated with a biotin-conjugated secondary antibody after being rinsed in PBS (Lab Vision Corporation, Fermont, USA). As a counterstain and chromogen, Mayer’s hematoxylin and DAB were employed. After that, PBS and distilled water were used to rinse the slides. The primary antibodies were left out of the staining technique to create negative control slides.
When brown staining was found in the cell membrane of any number of cells, the samples were categorized as positive for E-cadherin. The expression was only evaluated in epithelial cells because it was challenging to determine the expression of membranes in stromal cells . Vimentin immunostaining on epithelial cells was expressed as positive or negative . The scoring was performed by two independent observers, and the discordant cases were reanalyzed to reach a consensus.
Transmission electron microscopy of the testis
For transmission electron microscopy, the samples of testis were sectioned into pieces (1 mm×1 mm×1 mm), fixed in 5% glutaraldehyde, then washed and postfixed. The tissue was dried using ethanol at increasing concentrations. Sections as thin as 60–70 nm were sliced. A transmission electron microscope was used to examine the sections (JEOL Ltd, Japan).
The data were collected, tabulated, and underwent statistical analysis via Statistical Package for the Social Sciences (SPSS), version 22 (2013; IBM Corp., Armonk, New York, USA). There were two kinds of statistics performed: descriptive statistics were performed for quantitative data: mean and SD, and analytic statistics were done using analysis of variance test to figure out the differences between all cohorts, and then the post-hoc Tukey test was done to figure out the change between each pair of the group. At a 95% confidence level and a P value of less than 0.05, the level of significance was determined, and results are displayed in the table. The sample size for the animal study was calculated using the G-power tool using an effect size of 0.6, a power of 0.9, and a significance level of 0.05. According to this, 30 animals were needed, with six animals in each group. Using univariate analysis, all variables were examined for a normal distribution.
Fertility hormones: as depicted in Table 1, BPA treatment induced a substantial decrease (P<0.05) in the average outcomes of LH, FSH, as well as testosterone than controls. The cotreatment with CoQ10 markedly increased the plasma fertility hormones than the BPA group and recovered them to almost normal levels.
Antioxidant parameters:Table 2 shows that BPA administration markedly (P<0.05) decreased serum SOD and CAT and increased MDA than controls. In contrast, the average outcomes of serum SOD and CAT were significantly increased, and MDA was substantially diminished in rats administered BPA+CoQ10 compared with BPA-administered rats.
Semen analysis parameters:Table 3 shows the semen parameter modifications in all the groups studied. Rats who were administrated BPA demonstrated a substantial decline (P<0.05) in the total proportion of sperm and progressive motility, viability, and count than controls, whereas % of abnormal forms demonstrated marked elevation (P<0.05). The cotreatment with CoQ10 increased the % of sperm total and progressive motility, viability, and count, whereas the % of abnormal forms demonstrated a substantial decline (P<0.05) than the BPA cohort and regained these parameters to almost typical values.
Light microscopic results of prostate
Hematoxylin and eosin
- Negative and positive control groups (I, II, and III): the H&E-stained sections of the prostate showed normal structure formed of acini of regular size and shapes surrounded by a delicate layer of fibromuscular stroma containing blood capillaries lined with simple columnar epithelium with basal nuclei (Fig. 1).
- Bisphenol group (IV): the prostate revealed proliferative features, being more prominent in BPA groups compared with the control groups, acini showed disturbed architecture, and glandular prostatic hyperplasia was surrounded by stromal hyperplasia with focal papillary projections in the lumen when compared with control and CoQ10+bisphenol groups. Some acini contained acidophilic secretions. The interstitial space contained more congested blood vessels, connective tissue, and small dark monocellular inflammatory cells (Fig. 2).
- CoQ10+bisphenol group (V): the acini were lined by simple columnar epithelium with slight hyperplasia and few papillary projections toward the alveolar lumen. The acini were surrounded by slightly thick fibromuscular stroma. The interstitial space contained scanty connective tissue and congested blood vessels (Fig. 3).
The immunohistochemically stained sections of the negative and positive controls (I, II, and III) of the prostate with E-cadherin and vimentin showed the same immunoreactivity, which appeared as the membranous expression of epithelial cells and stroma expression, respectively, compared with BPA-treated group (VI), which showed gradually diminished E-cadherin expression as well as minimally elevated vimentin expression in epithelial cells. However, the CoQ10+bisphenol group (V) showed gradually focal increased E-cadherin membranous expression in epithelial cells as well as stromal vimentin expression (Figures 4-9).
Electron microscopic results of testes
- Negative and positive control groups (I, II, and III): the seminiferous tubule’s basal lamina appeared intact and smooth. No evidence of morphological abnormalities was observed. Normal Sertoli cells were detected with indented nuclei lying on a thin, normal basement membrane surrounded by the flat nuclei of myoid cells and Leydig cells. Spermatogenetic activity and seminiferous tubular structure were normal. Spermatids, spermatocytes, and spermatogonium were highly developed and well organized. The spermatogonia cells are close to the Sertoli cells and also on the basement membrane. In the second layer, primary spermatocytes with big nuclei appeared. The seminiferous tubules showed the lumen filled with spermatozoa flagella (Fig. 10).
- Bisphenol group (IV): the seminiferous tubule’s basal lamina turned thicker and rougher, and further spermatid abnormalities were detected. In comparison with the control groups, acrosomal caps and spermatid acrosomal vesicles were distorted, the intercellular gap between Sertoli cells expanded, and tight connections were damaged or even eliminated. The spermatogonial cells’ cytoplasm and the neighboring Sertoli cells look deteriorated, with inflated mitochondria and larger intracellular vacuoles, cytoplasmic vacuoles (Fig. 11).
- CoQ10+bisphenol group (V): this group’s rat testis experienced a substantial enhancement in testis contents. The basal lamina was able to reestablish its normal shape. Both the spermatogonia and basement membrane appeared normal. The spermatids, sperms, and spermatocytes retained their normal structure (Fig. 12).
BPA is considered an endocrine disruptor that binds to estrogen receptor subtypes (ER) and activates them . BPA may also interfere with androgenic signaling pathways, which are critical for developing the sex organs of males as well as reproductive activities .
Regarding the present study, BPA treatment demonstrated a substantial decline (P<0.05) in the mean values of LH, FSH, as well as testosterone than controls.
These findings support those of Gurmeet et al. , Hassan et al. , Xi et al. , as well as Nakamura et al. , who discovered a significant drop in testosterone levels after BPA treatment. Based on Xi et al.  and Nakamura et al. , the lower blood testosterone level may be due to the diminished steroidogenic enzyme expression as well as cholesterol carrier protein involved in testosterone production. In line with these findings, Akingbemi et al.  discovered diminished free plasma testosterone levels and 17-oestradiol in animals treated with BPA. They concluded that testosterone production was reduced because of BPA’s direct action on Leydig cells. This hypothesis was based on their discovery that BPA suppressed aromatase gene expression, resulting in decreased 17-oestradiol biosynthesis. Aromatase is an enzyme that is required for the aromatization of testosterone to 17-oestradiol . Additionally, it has been reported that BPA has an antiandrogenic effect by inhibiting the action of dihydrotestosterone .
LH, FSH, and testosterone are all required for spermatogenesis. The pituitary gland generates LH, which stimulates the production of testosterone. On the contrary, testosterone is required for sperm production and maintenance . In addition, testosterone and FSH promote spermatid development as well as sperm release . In our study, BPA administration diminished LH, FSH, and testosterone levels, which can be attributed to the effect on Leydig and Sertoli cells. Our findings are compatible with those of previous research, in which BPA impaired the function of Sertoli cells and altered the hypothalamic–pituitary–gonadal axis .
Furthermore, previous research suggested that the reduction in testosterone in rats treated with BPA was caused by interfering with the proliferation as well as Leydig cell function . Akingbemi et al.  illustrated that BPA affects the pituitary gland as well as impairs the activity of testicles, alleviating the release of LH. It has been revealed that BPA reduces the production of testosterone from Leydig cells by inhibiting the activity of 17-hydroxylase or elevating the activity of aromatases . In addition, Alboghobeish et al.  found a decline in serum FSH, LH, estradiol, and testosterone in animals treated with BPA. According to Grami et al. , testosterone and the levels of LH in serum were significantly lower in the cohort treated with BPA than in controls.
In our study, the cotreatment with CoQ10 significantly increased the plasma fertility hormones than the BPA cohort and restored them to nearly normal levels. This effect could be attributed to CoQ10’s direct or indirect effect on cellular oxidative damage. According to Ramadan et al. , CoQ10 administration increased serum testosterone levels in male rats treated with sodium arsenite . El-Khadragy et al.  discovered that CoQ10 could improve testicular function even when Pb was present. Both the relative and absolute weight of testicles was recovered after CoQ10 treatment, as were the levels of FSH, LH, and testosterone; indicators of oxidative stress were decreased, as demonstrated by the lower concentrations of LPO and NO.
The present study revealed that administration of PBA substantially (P<0.05) decreased serum SOD and CAT and increased MDA than controls. In contrast, the mean serum SOD and CAT values were markedly elevated. MDA was substantially diminished in rats administered BPA+CoQ10 than BPA-administered rats.
BPA treatment resulted in higher lipid peroxidation levels , in addition to a diminished testicular antioxidant (SOD ad CAT) system [21,61]. Our findings align with those of Gülecs et al. , who found that CoQ10 administration in the CoQ10-BPA cohort lowered the levels of testicular MDA while increasing the levels of testicular GSH in the presence of BPA. As a result, CoQ10 was found to reduce the effect of oxidative stress in BPA toxicity. Treatment with BPA elevated the levels of serum MDA, whereas treatment with CoQ10 diminished the levels of MDA in the CoQ10-BPA cohort. According to these findings, BPA serves as an oxidative stress activator, whereas CoQ10 can be an antioxidant source that manages to reduce oxidative stress by diminishing MDA levels. CoQ10 administration in the CoQ10-BPA cohort preserved plasma GSH and serum SOD activity. El-Khadragy et al.  found that CoQ10 improved the level and expression of glutathione and the antioxidant enzymes CAT, SOD, GPx, and GR.
The present study showed BPA-administered rats showed a substantial decrease (P<0.05) in the total proportion of sperms as well as progressive motility, viability, and count as compared with controls, whereas the proportion of abnormal forms demonstrated a marked decline (P<0.05). The cotreatment with CoQ10 increased the % of sperm total and progressive motility, viability, and count, whereas the % of abnormal forms demonstrated a substantial decline (P<0.05) than the BPA cohort and recovered these outcomes approximately to normal values.
This finding aligns with Salian et al. , who found that prenatal and neonatal BPA exposure affects the offspring’s testicular development and spermatogenesis during adulthood. Several studies illustrated that BPA has a variety of effects on the reproductive system of males. Additionally, Tiwari and Vanage  investigated the effect of BPA on sperm count and efficiency in the testes, which resulted in a decline in the quality and productivity of sperm. Furthermore, Karnam et al.  demonstrated that male rats exposed to BPA experienced alleviated sperm count and motility. Shi et al.  demonstrated that oxidative stress induced by BPA exposure reduced sperm count by reducing spermatogonia, spermatocytes, and spermatids. ElGendy et al.  discovered diminished progression, sperm motility, and count at the lowest dose of BPA (50g/kg b.w.), with the greatest effect appearing after 3 weeks of exposure. Their findings imply that exposure to BPA diminishes male rats’ fertility by impairing the production of sperm, quality, and motility. Furthermore, BPA reduced epididymal sperm motility as well as count in adult males. Alboghobeish et al.  and Alabi et al.  indicated that BPA alters the quality of sperm cells, in addition to substantially lowering the number of sperm cells in mice during spermatogenesis. The alleviation in the quantity of sperm in these animals can be attributed to the damaging effect of BPA on Sertoli cells that determine the volume of the produced sperm cells. According to Gülecs et al. , higher midpiece deformities in the BPA cohort demonstrated the BPA’s toxic effect at the region of caput epididymis. This site’s elevated flow of blood, as well as metabolic activity, makes it more prone to oxidative stress. As sperm undergoes morphological maturity in this area, the likelihood of developing morphological defects would be increased . Furthermore, administration of CoQ10 increased the daily production of sperms, motility, and concentration in male mice exposed to a magnetic field . In the study by Gülecs and colleagues, no substantial differences were detected between the BPA and CoQ10-BPA groups. Nevertheless, the CoQ10-BPA group had a numerical drop in the abnormalities sperm. The presence of numerically diminished abnormalities of sperm in the CoQ10-BPA cohort suggests that CoQ10 may play a protective role in testicular regions. CoQ10 efficacy can be questioned by altering the route or dose of administration, as reported by Gülecs et al. . According to Lukacova et al. , treatment of BPA elevated cells’ superoxide levels as well as diminished the motility and viability of beef bull sperm. According to Gülecs et al. , treatment with BPA reduced the viability of sperm more than the control and vehicle control groups. This decline in the viability of sperm following BPA treatment can be attributed to diminished antioxidative ability and increased oxidative stress. In the CoQ10-BPA group, treatment with CoQ10 exhibited a potential favorable effect on the viability of sperm, but it was statistically insignificant. In addition, increased dose levels of CoQ10 in the CoQ10-BPA cohort may demonstrate the CoQ10’s effect on the viability of sperm.
The current work demonstrated that BPA administration resulted in several pathological alterations in the prostate structure and the ultrastructure of testis compared with control groups. These changes on the prostate revealed congestion in the connective tissue and benign nodular prostatic hyperplasia. Our findings go hand in hand with the results of Shalaby et al. , Tolba and Mandour , and Hussein , where the histopathological examination revealed mild to severe papillary hyperplasia in the lining epithelia with focal thickening in the prostate gland of BPA-treated rats. Moreover, Hassan et al.  also detected papillary hyperplasia in the lining epithelia with decreased prostatic secretion in the prostate gland of rats pre- and postnatally exposed to BPA. Furthermore, these results are similar to the findings of Huang et al. , who revealed that the prostate gland is estrogen sensitive and that exposure to synthetic estrogens changes prostate growth and differentiation. These effects are caused by the oxidative stress promoted by BPA, which will result in severe consequences over a lengthy period of exposure. According to Hasanluyi et al. , the interstitial space in our investigation has clogged blood arteries. Kathryn and McCance  describe the process of blood vessel dilatation, stating that an elevation in the oxygen ratio induces an elevation in the rate of adenosine synthesis, resulting in dilatation of vessels and higher flow of blood to maintain the ratio of oxygen to normal values.
Typically, epithelial cells form an aligned apical-basal polarity when they adhere to the basement membrane. Because of their contact with the basement membrane, epithelial cells are prevented from penetrating the extracellular matrix beneath the epithelium and staying inside the epithelium (ECM). In EMT, epithelial cells become more mobile and fibroblast like, losing their stability, while also losing epithelial marker expression such as desmoplakin, E-cadherin, and cytokeratins .
In the current investigation, we discovered a decrease in E-cadherin expression in prostatic specimens’ epithelial layer; moreover, hyperplastic glands expressed more vimentin than the neighboring healthy glands. This was noticed mainly in subnuclear region of the epithelium and in the stromal cells associated with these glands. Vimentin is the mesenchymal marker most associated with EMT and has been described to be upregulated in BPH .
This finding is consistent with Huang et al. , who discovered the dose is 10 μg/kg/day BPA dramatically increased vimentin expression while decreasing that of E-cadherin. This is in line with Alonso-Magdalena et al. , who found that E-cadherin was downregulated in areas where epithelial cells assumed an elongated shape and were no longer connected to the basement membrane, as well as elevated vimentin expression in hyperplastic glands, indicating that BPH was not a result of stromal cell growth. However, the accumulation of cells that resemble mesenchymal tissue and are generated from the prostatic epithelium because EMT can result in BPH and BPA can cause EMT.
BPA has been shown to pose a number of possible concerns to animal and human health. It has been shown that BPA causes toxicity in cells via oxidative stress-associated mitochondrial apoptotic pathways . CoQ10 acts as an antioxidant in lipid membranes and mitochondria as well as is involved in a variety of cellular activities . In our study, we observed that coadministration of CoAQ10 induced partial improvement in histopathological structure in prostate specimens of the rats. CoQ10 has been found in animal models to reduce apoptosis by inhibiting oxidative stress . In recent years, research studies that revealed that CoQ10 might protect against BPA-induced toxicity established the protective effect of COA Q10 on prostate damage and dysfunction [36,78,79].
In this work, we discovered ultrastructural alterations in BPA-treated male rats’ seminiferous tubules, such as significant cytoplasmic vacuolation of specific lining cells, compared with control groups. This is in accordance with Rahman and Pang , who discovered alterations in testicular cells like enlarged electron-dense bodies and intracellular vacuoles, cytoplasmic vacuoles, cell debris, and swollen mitochondria. These findings were due to an osmotic and imbalance inducing suppression of water, resulting in cellular vacuolation, which is identified as a type of cell deterioration .
Additionally, the smooth endoplasmic reticulum’s dilatation, which can be an indication of alterations in cellular permeability, may be the cause of the vacuolization of the germinal cells . Additionally, the ultrastructural findings pointed to induced degenerative changes in the basement membrane, retaining the structural and functional integrity of the testicular tissues . It is also consistent with Blanco-Rodriguez and Martinez-Garcia , who observed that the testosterone is necessary for the attachment of various generations of germ cells in seminiferous tubules, and BPA-induced lipid peroxidation and decreased testosterone levels may be the cause of ultrastructural abnormalities in the testis of BPA-treated male rats. Therefore, low levels of intratesticular testosterone may cause the germ cells to separate from the seminiferous epithelium, which would then cause the germ cells to undergo apoptosis, which would result in male infertility. Numerous lines of research examine the protective role of both natural and synthetic antioxidants in shielding the male reproductive system from the harmful effects of xenobiotics [80,83]. Moreover, we observed abnormalities in the spermatids and nuclei of the spermatids, and spermatozoa were severely deformed. The same results were mentioned by others [84,85].
When compared with the group that received BPA alone, the results of the current study showed a significant improvement in the testicular structure in the group that received BPA with CoQ10.. There have been claims that CoQ10 lowers the activity of testicular germ cell apoptosis and prevents testicular oxidative stress by increasing the antioxidant status . Our inability to address the dose response of BPA in this study is a major limitation because we did not examine different BPA dosages. The second study restriction is the lack of weight information for the prostate, tests, and epididymis due to some logistical challenges.
Conclusion and recommendations
This study’s biochemical and histopathological results revealed direct evidence for BPA-induced male reproductive toxicity, including testicular changes, hypospermia, and benign prostatic hyperplasia derived from the epithelium by a process called EMT inducing male infertility. CoQ10 coadministration with BPA partially hindered these effects, providing a positive and empowering preventive effects against environmental and occupational contaminants. As a result, it is advised to use other secure alternatives instead of using plastic products that contain BPA on a regular basis. Workers at plastic manufacturers should also be protected and given regular follow-ups. Additionally, our findings might have ramifications for how other endocrine disruptors affect human health and for further investigation of the adverse effect of BPA on male reproductive health at the genetic and molecular scales.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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