Ameliorative Effects of Zinc Oxide, in Either Conventional or Nanoformulation, Against Bisphenol A Toxicity on Reproductive Performance, Oxidative Status, Gene Expression and Histopathology in Adult Male Rats.

Bisphenol A (BPA) is a widely used endocrine disruptor that represents a significant risk to male reproductive function. Zinc (Zn) is vital for appropriate development of testes and to guarantee optimal testicular function and spermatogenesis. Our goal was to investigate if zinc oxide (ZnO), either in conventional or nanoformulation, could safeguard adult male rats' reproductive performance against the damaging effects of BPA. Signaling expression of CYP11A1 and Nrf-2 in the testis, testicular oxidant-antioxidant status, Bax/Bcl-2 apoptotic ratio, and histological examination of various reproductive organs were all evaluated. Twenty-eight adult male albino rats were divided randomly into 4 groups (7 animals each) including the control, BPA, conventional zinc oxide (cZnO) + BPA, and zinc oxide nanoparticles (ZnO-NPs) + BPA groups. The study was extended for 2 successive months. Our findings revealed strong negative effects of BPA on sperm cell characteristics such as sperm motility, viability, concentration and abnormalities. Additionally, BPA reduced serum levels of testosterone, triiodothyronine (T3), and thyroxine (T4). Also, it evoked marked oxidative stress in the testes; elevating malondialdehyde (MDA) and reducing total antioxidant capacity (TAC). BPA significantly downregulated testicular mRNA relative expression levels of CYP11A1 and Nrf-2, compared to control. Testicular apoptosis was also prompted by increasing Bax/ Bcl-2 ratio in testicular tissue. Histopathological findings in the testes, epididymis, prostate gland, and seminal vesicle confirmed the detrimental effects of BPA. Interestingly, cZnO and ZnO-NPs significantly alleviated all negative effects of BPA, but ZnO-NPs performed better. In conclusion, our findings point to ZnO, specifically ZnO-NPs, as a viable treatment for BPA-induced testicular dysfunction.

The protective effects of date seeds, in either conventional or nanoformulation, against bisphenol A-induced testicular toxicity: involvement of testicular expression of CYP11A1, Nrf-2 and Bax/Bcl-2 ratio.

Background: Bisphenol A (BPA), an endocrine-disrupting chemical (EDC), is ubiquitous in our environment and poses a significant threat to male fertility. Date seeds (DSs) are used in folk medicine due to their antioxidant activity. Aim: The purpose of this study was to assess the beneficial effects of DSs, whether in powder or nanoparticle form, against BPA-induced testicular oxidative challenges and apoptosis, aided by inspection of specific genes linked to fertility, oxidative stress and intrinsic mitochondrial pathway of apoptosis. Methods: Thirty-five adult male albino rats were equally divided into 5 groups including control, BPA, BPA + date seeds powder "DSP", BPA + date seed nanoparticle 1/10 (DSNP 1/10) and BPA + DSNP 1/20 groups. Results: TEM showed that the ball-mill method was effective to form DSNP with an average size of 20 nm. BPA significantly impaired sperm motility, morphology, viability and concentration. It also reduced serum testosterone levels and evoked marked oxidative stress in the testes. Additionally, serum levels of triiodothyronine and thyroxine were extremely reduced. Moreover, testicular mRNA relative expression levels of CYP11A1 and Nrf-2 were markedly downregulated. Testicular apoptosis was also promoted whereas Bax/Bcl-2 ratio was profoundly elevated. Histological pictures of the testes, epididymis, seminal vesicles and prostate confirmed the unfavorable effects of BPA. Surprisingly, we first demonstrated that DSs, specifically the nanoparticle form, strongly alleviated all of BPA's negative effects, with DSNP 1/20 achieving the best results. Conclusion: Therefore, DSNP in both doses could be regarded as an ideal candidate for abating the male reproductive challenges caused by BPA.

Developmental Programming: Physiological Impacts of Prenatal Melatonin Administration on Reproductive Capacity and Serum Triiodothyronine of Adult Female Offspring Rat Born to Moms Exposed to Bisphenol A During Pregnancy.

Gestational bisphenol A (BPA) exposure induced multiple programmed diseases in the adult offsprings. Thus, this study targeted exploring the physiological impacts of melatonin (MEL) as a reprogramming strategy against in utero BPA exposure on reproductive capacity of adult F1 female rat offspring. Forty adult pregnant albino female rats were divided equally into 5 groups (n = 8): group I (control), group II (low-dose BPA; 25 µg BPA/kg B.w.t.), group III (low-dose BPA + 10 mg MEL/kg B.w.t.), group IV (high-dose BPA; 250 µg/kg B.w.t.), and group V (high-dose BPA + MEL). Treatments were given daily by subcutaneous (s/c) injection from the fourth day of pregnancy until full term. After delivery, female offspring were selected, and on postnatal day 60, adult offspring were examined for estrus regularity and then were sacrificed at estrus to collect blood and tissue samples. Findings clarified that in utero BPA exposure (both doses) increased significantly (P < 0.05) the ovarian weights and the serum levels of estrogen but decreased that of triiodothyronine (T3) compared to control groups. Significant increasing of serum malondialdehyde (MDA) and decreasing of total antioxidant capacity (TAC) were also detected. Both doses of BPA disturbed remarkably the estrus cycles and caused marked aberrations in ovarian and uterine tissues. Interestingly, prenatal MEL co-treatment with BPA mitigated significantly all of these degenerative changes. Thus, this study first demonstrated that prenatal MEL therapy could be used as a potent reprogramming intervention against BPA-induced reproductive disorders in the adult F1 female rat offspring.