Molecular Biology, Cell Biology, Reproductive Medicine, Development
7
Scopus Publications
168
Scholar Citations
6
Scholar h-index
5
Scholar i10-index
Scopus Publications
The impact of junk food on male fertility in mice: therapeutic interventions targeting advanced glycation end-products and oxidative stress Z. Darmishonnejad, V. Hassan Zadeh, M. Tavalaee, A. Moazamian, R. J. Aitken, J. R. Drevet, P. Gharagozloo, M. H. Nasr-Esfahani Scientific Reports, 2026 Frequent consumption of poor-quality diets "junk food" leads to the accumulation of sugar-derived advanced glycation end-products (AGEs), promoting inflammation and oxidative stress (i.e., diminished endogenous antioxidant defenses). This biology has been linked to reduced male fertility, but it is unclear whether reversing AGE damage or boosting antioxidant defenses can restore reproductive function. We used a mouse model to test two approaches: Alagebrium (ALT-711), an investigational drug which breaks AGE cross-links, and Fertilix®, an antioxidant micronutrient blend. Sixty-eight male C57BL/6 mice were fed either a standard or AGE-rich diet, then treated for 35 days and mated. The AGE-rich diet raised glycation and metabolic markers, increased oxidative stress, disrupted spermatogenesis, and produced poorer sperm (lower counts and motility, more DNA damage). These changes translated into fewer pregnancies, more miscarriages, and smaller litters. Both interventions corrected many redox-related sperm defects, but only Fertilix® restored reproductive outcomes to near normal levels in AGE-fed animals; ALT-711 improved some measures yet did not rescue fertility and in fact worsened pregnancy metrics in healthy controls. These findings implicate AGE-driven oxidative stress as a modifiable driver of diet-related male infertility and support targeted antioxidant repletion to restore fertility; confirmation in clinical trials, albeit challenging, is warranted.
Effects of Acute Exposure to Methylglyoxal or/and A Diet Rich in Advanced Glycation End Products on Sperm Parameters in Mice Zahra Darmishonnejad, Vahideh Hassan-Zadeh, M. Tavalaee, Farzad Kobarfard, P. Gharagozloo, J. Drevet, M. Nasr-Esfahani International Journal of Fertility and Sterility, 2024 Background: Advanced glycation end products (AGEs) that accompany many metabolic disorders including diabetes, obesity, and a wide range of dyslipidemia conditions, are strongly associated with adverse effects on cell and tissue homeostasis. Accordingly, our objective was to investigate the impact of AGE-promoting diets on mouse models, considering both scenarios with and without methylglyoxal (MGO) as a primary precursor of AGEs. Materials and Methods: In this experimental study, 5-week-old C57BL/6 mice were split into four groups as a control group (n=5), AGE (n=5), MGO (n=8), and AGE-MGO-diets (n=8). After five weeks the level of fasting blood sugar (FBS), body weight, food intake, sperm parameters, and functional tests were evaluated. Furthermore, testicular superoxide dismutase (SOD) activity, malondialdehyde, and total antioxidant capacity (TAC) were assessed. Results: After five weeks, AGE, AGE-MGO, and MGO groups showed the highest level of body weight and FBS in comparison to the control group. Mean sperm concentration, sperm malondialdehyde, testicular lipid peroxidation, and TAC did not differ significantly among the study groups. While, AGE, MGO, and AGE-MGO groups showed a significant reduction in sperm motility and progressive motility compared to the control group (P<0.05). The greatest increases in abnormal sperm morphology and intracytoplasmic reactive oxygen species (ROS) were observed in the MGO and AGE-MGO groups than in the control group (P<0.05). Sperm protamine deficiency and residual histone were significantly increased in the three treatment groups compared to the control group (P<0.05). Regarding the DNA damage, the AGE and AGE-MGO groups showed the most severe damage. The lowest amount of testicular superoxide dismutases (SOD, P<0.001) was observed in the AGE-MGO group. Conclusion: AGEs and MGO have a negative influence on sperm function and reproductive potential. These effects could be possibly attributed to both increased oxidative stress (OS) and inflammation.
Sperm chromatin structure assay (SCSA®) and flow cytometry-assisted TUNEL assay provide a concordant assessment of sperm DNA fragmentation as a function of age in a large cohort of approximately 10,000 patients Paria Behdarvandian, Ali Nasr-Esfahani, Marziyeh Tavalaee, Kosar Pashaei, Nushin Naderi, Zahra Darmishonnejad, Jorge Hallak, Robert J. Aitken, Parviz Gharagozloo, Joël R. Drevet, Mohammad Hossein Nasr-Esfahani Basic and Clinical Andrology, 2023 Background Sperm DNA integrity is increasingly seen as a critical characteristic determining reproductive success, both in natural reproduction and in assisted reproductive technologies (ART). Despite this awareness, sperm DNA and nuclear integrity tests are still not part of routine examinations for either infertile men or fertile men wishing to assess their reproductive capacity. This is not due to the unavailability of DNA and sperm nuclear integrity tests. On the contrary, several relevant but distinct tests are available and have been used in many clinical trials, which has led to conflicting results and confusion. The reasons for this are mainly the lack of standardization between different clinics and between the tests themselves. In addition, the small number of samples analyzed in these trials has often weakened the value of the analyses performed. In the present work, we used a large cohort of semen samples, covering a wide age range, which were simultaneously evaluated for sperm DNA fragmentation (SDF) using two of the most frequently used SDF assays, namely the TUNEL assay and the sperm chromatin structure assay (SCSA®). At the same time, as standard seminal parameters (sperm motility, sperm morphology, sperm count) were available for these samples, correlations between age, SDF and conventional seminal parameters were analyzed. Results We show that the SCSA® and TUNEL assessments of SDF produce concordant data. However, the SDF assessed by TUNEL is systematically lower than that assessed by SCSA®. Regardless of the test used, the SDF increases steadily during aging, while the HDS parameter (High DNA stainability assessed via SCSA®) remains unchanged. In the cohort analyzed, conventional sperm parameters do not seem to discriminate with aging. Only sperm volume and motility were significantly lower in the oldest age group analyzed [50–59 years of age]. Conclusions In the large cohort analyzed, SDF is an age-dependent parameter, increasing linearly with aging. The SCSA® assessment of SDF and the flow cytometry-assisted TUNEL assessment are well correlated, although TUNEL is less sensitive than SCSA®. This difference in sensitivity should be taken into account in the final assessment of the true level of fragmentation of the sperm nucleus of a given sample. The classical sperm parameters (motility, morphology, sperm count) do not change dramatically with age, making them inadequate to assess the fertility potential of an individual.
Relationship between sperm telomere length and sperm quality in infertile men Zahra Darmishonnejad, Farzaneh Zarei‐Kheirabadi, Marziyeh Tavalaee, Masoumeh Zarei‐Kheirabadi, Dina Zohrabi, Mohammad Hossein Nasr‐Esfahani Andrologia, 2020 Telomeres, noncoding and repetitive DNA sequences play a significant function in chromatin integrity. Telomere length is age‐dependent in somatic cells, while it increases in sperm cell with age. Therefore, we aimed to assess sperm chromatin, leucocyte and sperm telomere length (LTL, STL) in spermatozoon of 38 infertile and 19 fertile men aged between 20 and 50 years. Protamine deficiency (chromomycin A3 test), DNA fragmentation (TUNEL assay), lipid peroxidation (Bodipy probe) and telomere length (quantitative real‐time PCR) were assessed. A significant decrease in mean of sperm concentration and motility and a significant increase in means of sperm abnormal morphology, DNA fragmentation, lipid peroxidation and protamine deficiency were observed in infertile compared with fertile men. In addition, the mean of LTL and STL were significantly shorter in infertile men compared with fertile individuals. We observed significant associations between telomere length with sperm concentration, DNA fragmentation and lipid peroxidation. We hypothesised that increased oxidative stress in spermatozoa of infertile men can result in abnormal packaging of chromatin, damage of DNA and shorter sperm telomere length. Together, these anomalies may account for fertility failure in these individuals.
The impact of junk food on male fertility: therapeutic interventions targeting advanced glycation end-products and oxidative stress in mice Z Darmishonnejad, V Hassan Zadeh, M Tavalaee, A Moazamian, ... Scientific Reports , 2026 2026
Effect of advanced glycation end products (AGEs) on sperm parameters and function in C57Bl/6 mice Z Darmishonnejad, VH Zadeh, M Tavalaee, F Kobarfard, M Hassani, ... Reproductive Sciences 31 (7), 2114-2122 , 2024 2024 Citations: 16
Sperm chromatin structure assay (SCSA ® ) and flow cytometry-assisted TUNEL assay provide a concordant assessment of sperm DNA fragmentation as a function … P Behdarvandian, A Nasr-Esfahani, M Tavalaee, K Pashaei, N Naderi, ... Basic and Clinical Andrology 33 (1), 33 , 2023 2023 Citations: 20
Effects of acute exposure to methylglyoxal or/and a diet rich in advanced glycation end products on sperm parameters Z Darmishonnejad, V Hassanzadeh, M Tavalaee, F Kobarfard, ... International Journal of Fertility and Sterility , 2023 2023 Citations: 6
The effect of alpha-lipoic acid on sperm functions in rodent models for male infertility: A systematic review N Naderi, Z Darmishonnejad, M Tavalaee, MH Nasr-Esfahani Life Sciences 323, 121383 , 2023 2023 Citations: 14
A-5 Sperm telomere length in infertile men with previous failed fertilization post-ICSI Z Darmishonnejad, M Tavalaee, T Izadi, S Tanhaei, MH Nasr-Esfahani International Journal of Reproductive BioMedicine 19 (5), 92-92 , 2021 2021
Relationship between sperm telomere length and sperm quality in infertile men Z Darmishonnejad, F Zarei‐Kheirabadi, M Tavalaee, M Zarei‐Kheirabadi, ... Andrologia 52 (5), e13546 , 2020 2020 Citations: 63
Distinctive deregulation of miR-27a and miR-27b in relapsing remitting multiple sclerosis J Shafiei, F Heidari, E Khashen, R Ghandehari‐Alavijeh, ... Journal of Basic Research in Medical Sciences 7 (2), 1-6 , 2020 2020 Citations: 2
Evaluation of sperm telomere length in infertile men with failed/low fertilization after intracytoplasmic sperm injection Z Darmishonnejad, M Tavalaee, T Izadi, S Tanhaei, MH Nasr-Esfahani Reproductive Biomedicine Online 38 (4), 579-587 , 2019 2019 Citations: 46
Role and function of telomere in reproduction M Tavalaee, T Izadi, NMH ESFAHANI Journal of Sabzevar University of Medical Sciences 26 (4), 460-476 , 2019 2019 Citations: 1
MOST CITED SCHOLAR PUBLICATIONS
Relationship between sperm telomere length and sperm quality in infertile men Z Darmishonnejad, F Zarei‐Kheirabadi, M Tavalaee, M Zarei‐Kheirabadi, ... Andrologia 52 (5), e13546 , 2020 2020 Citations: 63
Evaluation of sperm telomere length in infertile men with failed/low fertilization after intracytoplasmic sperm injection Z Darmishonnejad, M Tavalaee, T Izadi, S Tanhaei, MH Nasr-Esfahani Reproductive Biomedicine Online 38 (4), 579-587 , 2019 2019 Citations: 46
Sperm chromatin structure assay (SCSA ® ) and flow cytometry-assisted TUNEL assay provide a concordant assessment of sperm DNA fragmentation as a function … P Behdarvandian, A Nasr-Esfahani, M Tavalaee, K Pashaei, N Naderi, ... Basic and Clinical Andrology 33 (1), 33 , 2023 2023 Citations: 20
Effect of advanced glycation end products (AGEs) on sperm parameters and function in C57Bl/6 mice Z Darmishonnejad, VH Zadeh, M Tavalaee, F Kobarfard, M Hassani, ... Reproductive Sciences 31 (7), 2114-2122 , 2024 2024 Citations: 16
The effect of alpha-lipoic acid on sperm functions in rodent models for male infertility: A systematic review N Naderi, Z Darmishonnejad, M Tavalaee, MH Nasr-Esfahani Life Sciences 323, 121383 , 2023 2023 Citations: 14
Effects of acute exposure to methylglyoxal or/and a diet rich in advanced glycation end products on sperm parameters Z Darmishonnejad, V Hassanzadeh, M Tavalaee, F Kobarfard, ... International Journal of Fertility and Sterility , 2023 2023 Citations: 6
Distinctive deregulation of miR-27a and miR-27b in relapsing remitting multiple sclerosis J Shafiei, F Heidari, E Khashen, R Ghandehari‐Alavijeh, ... Journal of Basic Research in Medical Sciences 7 (2), 1-6 , 2020 2020 Citations: 2
Role and function of telomere in reproduction M Tavalaee, T Izadi, NMH ESFAHANI Journal of Sabzevar University of Medical Sciences 26 (4), 460-476 , 2019 2019 Citations: 1
The impact of junk food on male fertility: therapeutic interventions targeting advanced glycation end-products and oxidative stress in mice Z Darmishonnejad, V Hassan Zadeh, M Tavalaee, A Moazamian, ... Scientific Reports , 2026 2026
A-5 Sperm telomere length in infertile men with previous failed fertilization post-ICSI Z Darmishonnejad, M Tavalaee, T Izadi, S Tanhaei, MH Nasr-Esfahani International Journal of Reproductive BioMedicine 19 (5), 92-92 , 2021 2021
