Acute Myeloid Leukemia Affects Mouse Sperm Parameters, Spontaneous Acrosome Reaction, and Fertility Capacity

Michailov, Yulia; Lunenfeld, Eitan; Kapilushnik, J.; Friedler, Shevach; Meese, Eckart; Huleihel, Mahmoud

doi:10.3390/ijms20010219

Cited by 12 publications

(18 citation statements)

References 39 publications

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“…Sperm cells were extracted from the tail of the epididymis by squeezing in a Petri dish plate. Collected sperm from all examined groups of treated mice were examined for concentration and motility using a Makler counting chamber, as described previously [ 18 ]. Evaluation of sperm morphology was performed according to the WHO criteria [ 55 ], and as described previously [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

“…Although the precise mechanism has not yet been totally clarified, poor semen quality in these patients may be a result of endocrine/paracrine disturbances, systemic effects of cancer, or both [ 15 , 16 , 17 ]. Recently, we used an AML adult mice model and showed a significant reduction in testes weight, sperm parameters and fertility within weeks post injection [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Granulocyte Colony-Stimulating Factor Restored Impaired Spermatogenesis and Fertility in an AML-Chemotherapy Mice Model

Michailov

AbuMadighem²,

Lunenfeld³

et al. 2021

IJMS

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Leukemia and treatment of male patients with anticancer therapy (aggressive chemotherapy and/or radiotherapy) may lead to infertility or even permanent male sterility. Their mechanisms of spermatogenesis impairment and the decrease in male fertility are not yet clear. We showed that under acute myeloid leukemia (AML) conditions, alone and in combination with cytarabine (CYT), there was significant damage in the histology of seminiferous tubules, a significant increase in apoptotic cells of the seminiferous tubules, and a reduction in spermatogonial cells (SALL and PLZF) and in meiotic (CREM) and post-meiotic (ACROSIN) cells. In addition, we showed a significant impairment in sperm parameters and fertilization rates and offspring compared to control. Our results showed a significant decrease in the expression of glial cell line-derived neurotrophic factor (GDNF), macrophage colony-stimulating factor (MCSF) and stem cell factor (SCF) under AML conditions, but not under cytarabine treatment compared to control. In addition, our results showed a significant increase in the pro-inflammatory cytokine interleukin-1 (IL-1) alpha in whole testis homogenates in all treatment groups compared to the control. Increase in IL-1 beta level was shown under AML conditions. We identified for the first time the expression of GCSF receptor (GCSFR) in sperm cells. We showed that GCSF injection in combination with AML and cytarabine (AML + CYT + GCSF) extended the survival of mice for a week (from 6.5 weeks to 7.5 weeks) compared to (AML + CYT). Injection of GCSF to all treated groups (post hoc), showed a significant impact on mice testis weight, improved testis histology, decreased apoptosis and increased expression of pre-meiotic, meiotic and post- meiotic markers, improved sperm parameters, fertility capacity and number of offspring compared to the controls (without GCSF). GCSF significantly improved the spermatogonial niche expressed by increased the expression levels of testicular GDNF, SCF and MCSF growth factors in AML-treated mice and (AML + CYT)-treated mice compared to those groups without GCSF. Furthermore, GCSF decreased the expression levels of the pro-inflammatory cytokine IL-12, but increased the expression of IL-10 in the interstitial compartment compared to the relevant groups without GCSF. Our results show for the first time the capacity of post injection of GCSF into AML- and CYT-treated mice to improve the cellular and biomolecular mechanisms that lead to improve/restore spermatogenesis and male fertility. Thus, post injection of GCSF may assist in the development of future therapeutic strategies to preserve/restore male fertility in cancer patients, specifically in AML patients under chemotherapy treatments.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Granulocyte Colony-Stimulating Factor Restored Impaired Spermatogenesis and Fertility in an AML-Chemotherapy Mice Model

Michailov

AbuMadighem²,

Lunenfeld³

et al. 2021

IJMS

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“…It was shown that different types of cancers, including leukemia, lymphoma, testicular cancer, non-Hodgkin's disease, gastrointestinal malignancy, and musculoskeletal malignancy, affect sperm parameters and the quality of thawed cryopreserved sperm [7,8]. Recently, using a mature animal model of leukemia, we showed that acute myeloid leukemia (AML) significantly decreased sperm parameters, increased spontaneous acrosome reaction, and decreased both male fertility capacity and number of offspring [9]. Thus, cancer may lead to male subfertility/infertility.…”

Section: Cancer and Male Infertilitymentioning

confidence: 99%

“…In-vitro culture: Differentiation to SSCs 8,9 Intercourse or ART Fertility restoration (8) Needs more research for validation, safety, efficiency, and genetic stability (9) Not yet applicable in humans Differentiation of SSCs to sperm 8,9 ART…”

Section: Artmentioning

confidence: 99%

Approaches and Technologies in Male Fertility Preservation

Huleihel

Lunenfeld

2020

IJMS

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Male fertility preservation is required when treatment with an aggressive chemo-/-radiotherapy, which may lead to irreversible sterility. Due to new and efficient protocols of cancer treatments, surviving rates are more than 80%. Thus, these patients are looking forward to family life and fathering their own biological children after treatments. Whereas adult men can cryopreserve their sperm for future use in assistance reproductive technologies (ART), this is not an option in prepubertal boys who cannot produce sperm at this age. In this review, we summarize the different technologies for male fertility preservation with emphasize on prepubertal, which have already been examined and/or demonstrated in vivo and/or in vitro using animal models and, in some cases, using human tissues. We discuss the limitation of these technologies for use in human fertility preservation. This update review can assist physicians and patients who are scheduled for aggressive chemo-/radiotherapy, specifically prepubertal males and their parents who need to know about the risks of the treatment on their future fertility and the possible present option of fertility preservation.

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“…This study showed that the ejaculate modified gene expression in the endometrium and oviduct, and this was dependent on the sperm fraction considered. The effect of leukemia in sperm biology was studied in a murine model [4], showing that leukemia altered spermatozoa, increasing the spontaneous acrosome reaction, and decreasing the number of pups born. Ethanol is one of the major concerns in public health and is directly linked to numerous forms of cancer and mental problems.…”

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confidence: 99%