Neurodegenerative Diseases and Infertility

Yıl 2025, Cilt: 1 Sayı: 2, 123 - 134, 27.05.2025

Mehmet Emin Önger , Abubaker El Elhaj , Enis Kuruoglu

Öz

The exploration of potential connections between infertility cases and neurodegenerative diseases like Parkinson's or Alzheimer's, despite their unrelated nature. There are co-occurring processes between neurodegenerative diseases and infertility since both affect complex biological systems. Several genetic and physiological processes connect infertility and neurodegenerative diseases. Studies have indicated that distinct neurodegenerative diseases can cause infertility, particularly in males, because of hereditary and common molecular pathways. For instance, both neurodegenerative diseases and infertility may be influenced by oxidative stress, hereditary factors, or hormone abnormalities.Neurodegenerative illnesses have the potential to interfere with the hypothalamus-pituitary-gonadal HPG axis, which is essential for reproduction. For example, the hypothalamus may be impacted by Parkinson's disease, resulting in hormonal problems that influence fertility. Certain genes like Huntington's disease and dementia may affect reproductive health. These genes have CAG repeat increases and are common in NDs and Infertility due to mitochondrial malfunction, which stands essential for energy production in gametes and neurons. Oxidative stress, a common cause of chronic inflammation in conditions like Alzheimer's and neurodegenerative diseases, can damage reproductive organs and cause infertility by injuring cells, including germ cells and neurons. Neurodegenerative diseases, controlled by medications and psychological pressure, can indirectly affect fertility, showing hormonal changes and possible negative impacts on the body's overall health. New studies suggest possible links between human infertility and neurodegenerative diseases, involving genetic factors, shared the same biological pathways, hormonal dysregulation, and environmental factors.
This review emphasizes the complex and multifactorial characteristics of neurodegenerative diseases and infertility, highlighting the need to differentiate between direct and indirect relationships, acknowledge the presence of links, and call for additional investigation.

Anahtar Kelimeler

Neurodegeneration , Infertility , oxidative stress , HPG axis , Endocrine disruptors

Nörodejeneratif hastalıklar ve infertilite

Öz

The exploration of potential connections between infertility cases and neurodegenerative diseases like Parkinson's or Alzheimer's, despite their unrelated nature. There are co-occurring processes between neurodegenerative diseases and infertility since both affect complex biological systems. Several genetic and physiological processes connect infertility and neurodegenerative diseases. Studies have indicated that distinct neurodegenerative diseases can cause infertility, particularly in males, because of hereditary and common molecular pathways. For instance, both neurodegenerative diseases and infertility may be influenced by oxidative stress, hereditary factors, or hormone abnormalities.Neurodegenerative illnesses have the potential to interfere with the hypothalamus-pituitary-gonadal HPG axis, which is essential for reproduction. For example, the hypothalamus may be impacted by Parkinson's disease, resulting in hormonal problems that influence fertility. Certain genes like Huntington's disease and dementia may affect reproductive health. These genes have CAG repeat increases and are common in NDs and Infertility due to mitochondrial malfunction, which stands essential for energy production in gametes and neurons. Oxidative stress, a common cause of chronic inflammation in conditions like Alzheimer's and neurodegenerative diseases, can damage reproductive organs and cause infertility by injuring cells, including germ cells and neurons. Neurodegenerative diseases, controlled by medications and psychological pressure, can indirectly affect fertility, showing hormonal changes and possible negative impacts on the body's overall health. New studies suggest possible links between human infertility and neurodegenerative diseases, involving genetic factors, shared the same biological pathways, hormonal dysregulation, and environmental factors.
This review emphasizes the complex and multifactorial characteristics of neurodegenerative diseases and infertility, highlighting the need to differentiate between direct and indirect relationships, acknowledge the presence of links, and call for additional investigat

Anahtar Kelimeler

Kısırlık , Nörodejenerasyon , HPG ekseni , Endokrin bozucular

Kaynakça

• Abondio, P., Sazzini, M., Garagnani, P., Boattini, A., Monti, D., Franceschi, C., Luiselli, D. & Giuliani, C. (2019) The genetic variability of APOE in different human populations and its implications for longevity. Genes, 10, 222.
• Alsemari, A. (2013) Hypogonadism and neurological diseases. Neurological Sciences, 34, 629- 638. Basini, G. & Grasselli, F. (2024) Role of melatonin in ovarian function. Animals, 14, 644.
• Bi, N., Gu, X., Fan, A., Li, D., Wang, M., Zhou, R., Sun, Q.-C. & Wang, H.-L. (2022) Bisphenol- A exposure leads to neurotoxicity through upregulating the expression of histone deacetylase 2 in vivo and in vitro. Toxicology, 465, 153052.
• Chernykh, V., Solovova, O., Sorokina, T., Shtaut, M., Sedova, A., Bliznetz, E., Ismagilova, O., Beskorovainaya, T., Shchagina, O. & Polyakov, A. (2024) CAG n Polymorphic Locus of Androgen Receptor (AR) Gene in Russian Infertile and Fertile Men. International Journal of Molecular Sciences, 25, 12183. Colaco, S. & Sakkas, D. (2018) Paternal factors contributing to embryo quality. Journal of Assisted Reproduction and Genetics, 35, 1953-1968.
• Darabi, N., Mashayekhy, M., Borjian Boroujeni, P., Mohtasebi, P., Rokhsat Talab, Z. & Zamanian, M.R. (2024) APOE‐E4 allele as a potential marker for implantation failure: A comparison between fertile women, ART success and RIF patients. International Journal of Gynecology & Obstetrics, 167, 169-176.
• Erickson, R.P. (2018) Do GWAS and studies of heterozygotes for NPC1 and/or NPC2 explain why NPC disease cases are so rare? Journal of Applied Genetics, 59, 441-447. Espino, J., Macedo, M., Lozano, G., Ortiz, Á., Rodríguez, C., Rodríguez, A.B. & Bejarano, I. (2019) Impact of melatonin supplementation in women with unexplained infertility undergoing fertility treatment. Antioxidants, 8, 338. Fahy, N., Rice, C., Lahiri, N., Desai, R. & Stott, J. (2023)
• Genetic risk for Huntington Disease and reproductive decision‐making: A systematic review. Clinical Genetics, 104, 147-162.
• Fanlo-Ucar, H., Picón-Pagès, P., Herrera-Fernández, V., IllRaga, G. & Muñoz, F.J. (2024) The Dual Role of Amyloid BetaPeptide in Oxidative Stress and Inflammation: Unveiling Their Connections in Alzheimer’s Disease Etiopathology. Antioxidants, 13, 1208.
• Ferraguti, G., Fanfarillo, F., Tarani, L., Blaconà, G., Tarani, F., Barbato, C., Minni, A., Ralli, M., Francati, S. & Greco, A. (2022) NGF and the male reproductive system: potential clinical applications in infertility. International Journal of Molecular Sciences, 23, 13127.
• Fraczek, M. & Kurpisz, M. (2015) Cytokines in the male reproductive tract and their role in infertility disorders. Journal of Reproductive Immunology, 108, 98-104.
• Heimsch, K.C., Gertzen, C.G., Schuh, A.K., Nietzel, T., Rahlfs, S., Przyborski, J.M., Gohlke, H., Schwarzländer, M., Becker, K. & Fritz-Wolf, K. (2022) Structure and function of redoxsensitive superfolder green fluorescent protein variant. Antioxidants & Redox Signaling, 37, 1-18.
• Li, Y., Wang, Z., Andersen, C.L. & Ye, X. (2020) Functions of lysosomes in mammalian female reproductive system. Reproductive and Developmental Medicine, 4, 109-122.
• Lisco, G., Triggiani, V., Bartolomeo, N., Ramunni, M.I., Pelusi, C., De Pergola, G., Guastamacchia, E., Jirillo, E. & Giagulli, V.A. (2023) The role of male hypogonadism, aging, and chronic diseases in characterizing adult and elderly men with erectile dysfunction: a cross-sectional study. Basic and Clinical Andrology, 33, 5.
• Menéndez-González, M., Clarimón, J., Rosas-Allende, I., Blázquez, M., San Martín, E.S., García- Fernández, C., Lleó, A., Dols-Icardo, O., Illán-Gala, I. & Morís, G. (2019) HTT gene intermediate alleles in neurodegeneration: evidence for association with Alzheimer's disease. Neurobiology of Aging, 76, 215. e219-215. e214.
• Müller, K.I., Nilssen, Ø., Nebuchenykh, M., Løseth, S., Jonsrud, C., Hoem, G., Van Ghelue, M. & Arntzen, K.A. (2022) Kennedy disease in two sisters with biallelic CAG expansions of the androgen receptor gene. Neuromuscular Disorders, 32, 75-79.
• Park, Y.-J. & Pang, M.-G. (2021) Mitochondrial functionality in male fertility: from spermatogenesis to fertilization. Antioxidants, 10, 98.
• Petry, C.J., Burling, K.A., Barker, P., Hughes, I.A., Ong, K.K. & Dunger, D.B. (2021) Pregnancy serum DLK1 concentrations are associated with indices of insulin resistance and secretion. The Journal of Clinical Endocrinology & Metabolism, 106, e2413-e2422.
• Piekarska, K., Dratwa, M., Radwan, P., Radwan, M., BoguniaKubik, K. & Nowak, I. (2023) Pro- and anti-inflammatory cytokines and growth factors in patients undergoing in vitro fertilization procedure treated with prednisone. Frontiers in Immunology, 14, 1250488.
• Pivonello, C., Muscogiuri, G., Nardone, A., Garifalos, F., Provvisiero, D.P., Verde, N., De Angelis, C., Conforti, A., Piscopo, M. & Auriemma, R.S. (2020) Bisphenol A: an emerging threat to female fertility. Reproductive Biology and Endocrinology, 18, 1-33.
• Reshi, M.S., Mustafa, R.A., Javaid, D. & Haque, S. (2022) Pesticide toxicity associated with infertility Oxidative Stress and Toxicity in Reproductive Biology and Medicine: A Comprehensive Update on Male Infertility Volume II. Springer, pp. 59-69.
• Richardson, J.R., Fitsanakis, V., Westerink, R.H. & Kanthasamy, A.G. (2019) Neurotoxicity of pesticides. Acta Neuropathologica, 138, 343-362.
• Santi, D., Crépieux, P., Reiter, E., Spaggiari, G., Brigante, G., Casarini, L., Rochira, V. & Simoni, M. (2020) Folliclestimulating hormone (FSH) action on spermatogenesis: a focus on physiological and therapeutic roles. Journal of Clinical Medicine, 9, 1014.
• Selvaraj, K., Manickam, N., Kumaran, E., Thangadurai, K., Elumalai, G., Sekar, A., Radhakrishnan, R.K. & Kandasamy, M. (2020) Deterioration of neuroregenerative plasticity in association with testicular atrophy and dysregulation of the hypothalamic- pituitary-gonadal (HPG) axis in Huntington’s disease: A putative role of the huntingtin gene in steroidogenesis. The Journal of Steroid Biochemistry and Molecular Biology, 197, 105526.
• Valencia‐Olvera, A.C., Maldonado Weng, J., Christensen, A., LaDu, M.J. & Pike, C.J. (2023) Role of estrogen in women's Alzheimer's disease risk as modified by APOE. Journal of Neuroendocrinology, 35, e13209.
• Vegeto, E., Villa, A., Della Torre, S., Crippa, V., Rusmini, P., Cristofani, R., Galbiati, M., Maggi,A. & Poletti, A. (2020) The role of sex and sex hormones in neurodegenerative diseases. Endocrine Reviews, 41, 273-319.
• Wang, H., Lautrup, S., Caponio, D., Zhang, J. & Fang, E.F. (2021) DNA damage-induced neurodegeneration in accelerated ageing and Alzheimer’s disease. International Journal of Molecular Sciences, 22, 6748.
• Watanobe, H. & Hayakawa, Y. (2003) Hypothalamic interleukin-1β and tumor necrosis factor-α, but not interleukin-6, mediate the endotoxin-induced suppression of the reproductive axis in rats. Endocrinology, 144, 4868- 4875.
• Welch, G. & Tsai, L.H. (2022) Mechanisms of DNA damage‐ mediated neurotoxicity in neurodegenerative disease. EMBO Reports, 23, e54217.
• Xu, X., Wang, Z., Lv, L., Liu, C., Wang, L., Sun, Y.-n., Zhao, Z., Shi, B., Li, Q. & Hao, G.-m. (2024) Molecular regulation of DNA damage and repair in female infertility: A systematic review. Reproductive Biology and Endocrinology, 22, 103.
• Yildirim, R.M. & Seli, E. (Year) The role of mitochondrial dynamics in oocyte and early embryo development. Vol. 159, Seminars in Cell & Developmental Biology. Elsevier, City. p. 52- 61.
• Yu, C.G., Bondada, V., Ghoshal, S., Singh, R., Pistilli, C.K., Dayaram, K., Iqbal, H., Sands, M., Moore, K.L. & Bondada, S. (2019) Repositioning flubendazole for spinal cord injury. Journal of Neurotrauma, 36, 2618-2630.
• Zhou, L., Hossain, M.I., Yamazaki, M., Abe, M., Natsume, R., Konno, K., Kageyama, S., Komatsu, M., Watanabe, M. & Sakimura, K. (2018) Deletion of exons encoding carboxypeptidase domain of Nna1 results in Purkinje cell degeneration (pcd) phenotype. Journal of Neurochemistry, 147, 557-572.