Protective effects of camel whey protein against scrotal heat‐mediated damage and infertility in the mouse testis through YAP/Nrf2 and PPAR‐gamma signaling pathways

Badr, Gamal; Abdel-Tawab, Hanem S.; Ramadan, Nancy K; Ahmed, Samia F.; Mahmoud, Mohamed H.

doi:10.1002/mrd.22987

Cited by 16 publications

(6 citation statements)

References 73 publications

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“…cells increases in the mouse testis following chronic heat stress (Badr, Abdel-Tawab, Ramadan, Ahmed, & Mahmoud, 2018). To this point, no study has evaluated the role of Hippo signaling in mammalian testicular germ cells, but two studies have suggested a potential role for this pathway in germ cell development.…”

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confidence: 99%

Yes‐associated protein expression in germ cells is dispensable for spermatogenesis in mice

Nader

Levasseur

Zhang

et al. 2019

Genesis

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Yes-associated protein (YAP), a key effector of the Hippo signaling pathway, is expressed in the nucleus of spermatogonia in mice, suggesting a potential role in spermatogenesis. Here, we report the generation of a conditional knockout mouse model (Yap flox/flox ; Ddx4 cre/+ ) that specifically inactivates Yap in the germ cells. The inactivation of Yap in spermatogonia was found to be highly efficient in this model.The loss of Yap in the germ cells had no observable effect on spermatogenesis in vivo. Histological examination of the testes showed no structural differences between mutant animals and age-matched Yap flox/flox controls, nor was any differences detected in gonadosomatic index, expression of germ cell markers or sperm counts. Cluster-forming assay using undifferentiated spermatogonia, including spermatogonial stem cells (SSCs), also showed that YAP is dispensable for SSC cluster formation in vitro. However, an increase in the expression of spermatogenesis and oogenesis basic helix-loop-helix 1 (Sohlh1) and neurogenin 3 (Ngn3) was observed in clusters derived from Yap flox/flox ; Ddx4 cre/+ animals. Taken together, these results suggest that YAP fine-tunes the expression of genes associated with spermatogonial fate commitment, but that its loss is not sufficient to alter spermatogenesis in vivo. K E Y W O R D Sspermatogenesis, spermatogonia, transgenic mouse model, Yap

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mentioning

confidence: 99%

Yes‐associated protein expression in germ cells is dispensable for spermatogenesis in mice

Nader

Levasseur

Zhang

et al. 2019

Genesis

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“…Mohamed et al [ 20 ] reported that prophylactic CM administration improved spermatogenesis activity with the right spermatozoa percentage. Badr et al [ 60 ] reported the effects of camel whey protein in protecting mice’s testes from scrotal heat-induced damage and infertility. Moreover, Faraji et al [ 61 ] reported that the administration of silymarin to the cadmium chloride rats prevented changes in the testicular histological characteristics and testosterone levels in the blood.…”

Section: Discussionmentioning

confidence: 99%

Camel milk or silymarin could improve the negative effects that experimentally produced by aflatoxin B1 on rat’s male reproductive system

Hassaneen,

Hemeda,

El Nahas

et al. 2024

BMC Vet Res

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Background Camel milk and silymarin have many different beneficial effects on several animal species. Meanwhile, Aflatoxins are mycotoxins with extraordinary potency that pose major health risks to several animal species. Additionally, it has been documented that aflatoxins harm the reproductive systems of a variety of domestic animals. The present design aimed to investigate the impact of aflatoxin B1 (AFB1) on rat body weight and reproductive organs and the ameliorative effects of camel milk and silymarin through measured serum testosterone, testes pathology, and gene expression of tumor necrosis factor (TNF-α), luteinizing hormone receptor (LHR), and steroidogenic acute regulatory protein (StAR) in the testes. A total of sixty mature male Wister white rats, each weighing an average of 83.67 ± 0.21 g, were used. There were six groups created from the rats. Each division had ten rats. The groups were the control (without any treatment), CM (1 ml of camel milk/kg body weight orally), S (20 mg silymarin/kg b. wt. suspension, orally), A (1.4 mg aflatoxin/kg diet), ACM (aflatoxin plus camel milk), and AS (aflatoxin plus silymarin). Results The results indicated the positive effects of camel milk and silymarin on growth, reproductive organs, and gene expression of TNF-α, LHR, and StAR with normal testicular architecture. Also, the negative effect of AFB1 on the rat’s body weight and reproductive organs, as indicated by low body weight and testosterone concentration, was confirmed by the results of histopathology and gene expression. However, these negative effects were ameliorated by the ingestion of camel milk and silymarin. Conclusion In conclusion, camel milk and silymarin could mitigate the negative effect of AFB1 on rat body weight and reproductive organs.

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“…Additionally, YAP is involved in the heat stress mediated testicular damage. 35 In addition, the Hippo signalling pathway in skeletal muscle is involved in the regulation of exercise adaptation. 28 However, both the exercise (physiological limitation) and heat stress (environmental factor) are the most importantly predisposing factors for EHS.…”

Section: Discussionmentioning

confidence: 99%

“…The strong and rapid YAP activation in cancer cells was induced by heat stress for the expression of heat shock proteins, 26 which is also suggested by our analysis. Additionally, YAP is involved in the heat stress mediated testicular damage 35 . In addition, the Hippo signalling pathway in skeletal muscle is involved in the regulation of exercise adaptation 28 .…”

Section: Discussionmentioning

confidence: 99%

ACSL4 contributes to ferroptosis‐mediated rhabdomyolysis in exertional heat stroke

Peng

et al. 2022

J cachexia sarcopenia muscle

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Background Rhabdomyolysis (RM) is a common complication of exertional heat stroke (EHS) and constitutes a direct cause of death. However, the mechanism underlying RM following EHS remains unclear. Methods The murine EHS model was prepared by our previous protocol. RNA sequencing is applied to identify the pathological pathways that contribute to RM following EHS. Inhibition of the acyl‐CoA synthetase long‐chain family member 4 (ACSL4) was achieved by RNA silencing in vitro prior to ionomycin plus heat stress exposure or pharmacological inhibitors in vivo prior to heat and exertion exposure. The histological changes, the iron accumulation, oxidized phosphatidylethanolamines species, as well as histological evaluation and levels of lipid metabolites in skeletal muscle tissues were measured. Results We demonstrated that ferroptosis contributes to RM development following EHS. Ferroptosis inhibitor ferrostatin‐1 administration once EHS onset significantly ameliorated the survival rate of EHS mice from 35.357% to 52.288% within 24 h after EHS (P = 0.0028 compared with control) and markedly inhibited RM development induced by EHS. By comparing gene expression of between sham heat rest (SHR) (n = 3) and EHS (n = 3) mice in the gastrocnemius (Gas) muscle tissue, we identified that Acsl4 mRNA expression is elevated in Gas muscle tissue of EHS mice (P = 0.0038 compared with SHR), so as to its protein levels (P = 0.0001 compared with SHR). Followed by increase in creatine kinase (CK) and myoglobin (MB) levels, the labile iron accumulation, decrease in glutathione peroxidase 4 (GPX4) expression, and elevation of lipid peroxidation products. From in vivo and in vitro experiments, inhibition of Acsl4 significantly improves muscle cell death caused by EHS, thereby ameliorating RM development, followed by reduction in CK and MB levels by 30–40% (P < 0.0001; n = 8–10) and 40% (P < 0.0001; n = 8–10), restoration of GPX4 expression, and decrease in lipid peroxidation products. Mechanistically, ACSL4‐mediated RM seems to be Yes‐associated protein (YAP) dependent via TEA domain transcription factor1/TEA domain transcription factor4. Conclusions These findings demonstrate an important role of ACSL4 in mediating ferroptosis activation in the development of RM following EHS and suggest that targeting ACSL4 may represent a novel therapeutic strategy to limit the skeletal muscle cell death and prevent RM after EHS.

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Protective effects of camel whey protein against scrotal heat‐mediated damage and infertility in the mouse testis through YAP/Nrf2 and PPAR‐gamma signaling pathways

Cited by 16 publications

References 73 publications

Yes‐associated protein expression in germ cells is dispensable for spermatogenesis in mice

Yes‐associated protein expression in germ cells is dispensable for spermatogenesis in mice

Camel milk or silymarin could improve the negative effects that experimentally produced by aflatoxin B1 on rat’s male reproductive system

ACSL4 contributes to ferroptosis‐mediated rhabdomyolysis in exertional heat stroke

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