Generic placeholder image

Current Molecular Medicine


ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Review Article

Stem Cells as a Resource for Treatment of Infertility-related Diseases

Author(s): Jing Wang, Chi Liu, Masayuki Fujino, Guoqing Tong, Qinxiu Zhang, Xiao-Kang Li* and Hua Yan*

Volume 19, Issue 8, 2019

Page: [539 - 546] Pages: 8

DOI: 10.2174/1566524019666190709172636

open access plus


Worldwide, infertility affects 8-12% of couples of reproductive age and has become a common problem. There are many ways to treat infertility, including medication, intrauterine insemination, and in vitro fertilization. In recent years, stem-cell therapy has raised new hope in the field of reproductive disability management. Stem cells are self-renewing, self-replicating undifferentiated cells that are capable of producing specialized cells under appropriate conditions. They exist throughout a human’s embryo, fetal, and adult stages and can proliferate into different cells. While many issues remain to be addressed concerning stem cells, stem cells have undeniably opened up new ways to treat infertility. In this review, we describe past, present, and future strategies for the use of stem cells in reproductive medicine.

Keywords: Infertility, World Health Organization (WHO), stem cells, fertilization, IVF, IUI, ICSI.

Next »
Mehra BL, Skandhan KP, Prasad BS, Pawankumar G, Singh G, Jaya V. Male infertility rate: A retrospective study. Urologia 2018; 85(1): 22-4.
[] [PMID: 28967062]
Hansen KR, He AL, Styer AK, et al. Predictors of pregnancy and live-birth in couples with unexplained infertility after ovarian stimulation-intrauterine insemination. Fertil Steril 2016; 105(6): 1575-83.
Barratt CLR, Björndahl L, De Jonge CJ, et al. The diagnosis of male infertility: An analysis of the evidence to support the development of global WHO guidance-challenges and future research opportunities. Hum Reprod Update 2017; 23(6): 660-80.
[] [PMID: 28981651]
D’Antonio M, Woodruff G, Nathanson JL, et al. High-throughput and cost-effective characterization of induced pluripotent stem cells. Stem Cell Reports 2017; 8(4): 1101-11.
[] [PMID: 28410643]
Katz DJ, Teloken P, Shoshany O. Male infertility - The other side of the equation. Aust Fam Physician 2017; 46(9): 641-6.
[PMID: 28892594]
Wojsiat J, Korczyński J, Borowiecka M, Żbikowska HM. The role of oxidative stress in female infertility and in vitro fertilization. Postepy Hig Med Dosw 2017; 71(0): 359-66.
[] [PMID: 28513460]
Gunn DD, Bates GW. Evidence-based approach to unexplained infertility: A systematic review. Fertil Steril 2016; 105(6): 1566-74.
Ohannessian A, Loundou A, Gnisci A, Paulmyer-Lacroix O, Perrin J, Courbiere B. Unexplained infertility: Live-birth’s prognostic factors to determine the ART management. Minerva Ginecol 2017; 69(6): 526-32.
[PMID: 28598138]
Cissen M, Bensdorp A, Cohlen BJ, Repping S, de Bruin JP, van Wely M. Assisted reproductive technologies for male subfertility. Cochrane Database Syst Rev 2016. 2CD000360
[PMID: 26915339]
Sawaya RA, Jaffe J, Friedenberg L, Friedenberg FK. Vitamin, mineral, and drug absorption following bariatric surgery. Curr Drug Metab 2012; 13(9): 1345-55.
[] [PMID: 22746302]
Ray A, Shah A, Gudi A, Homburg R. Unexplained infertility: An update and review of practice. Reprod Biomed Online 2012; 24(6): 591-602.
[] [PMID: 22503948]
Inhorn MC, Patrizio P. Infertility around the globe: New thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update 2015; 21(4): 411-26.
[] [PMID: 25801630]
Mouka A, Tachdjian G, Dupont J, Drévillon L, Tosca L. In vitro gamete differentiation from pluripotent stem cells as a promising therapy for infertility. Stem Cells Dev 2016; 25(7): 509-21.
[] [PMID: 26873432]
Somigliana E, Paffoni A, Busnelli A, et al. Age-related infertility and unexplained infertility: An intricate clinical dilemma. Hum Reprod 2016; 31(7): 1390-6.
[] [PMID: 27060173]
Vanni VS, Viganò P, Papaleo E, Mangili G, Candiani M, Giorgione V. Advances in improving fertility in women through stem cell-based clinical platforms. Expert Opin Biol Ther 2017; 17(5): 585-93.
[] [PMID: 28351161]
Brunauer R, Alavez S, Kennedy BK. Stem cell models: A guide to understand and mitigate aging? Gerontology 2017; 63(1): 84-90.
[] [PMID: 27760416]
Balen AH, Morley LC, Misso M, et al. The management of anovulatory infertility in women with polycystic ovary syndrome: An analysis of the evidence to support the development of global WHO guidance. Hum Reprod Update 2016; 22(6): 687-708.
[] [PMID: 27511809]
Asemota OA, Klatsky P. Access to infertility care in the developing world: The family promotion gap. Semin Reprod Med 2015; 33(1): 17-22.
[] [PMID: 25565507]
Scaparrotta A, Chiarelli F, Verrotti A. Potential Teratogenic Effects of Clomiphene Citrate. Drug Saf 2017; 40(9): 761-9.
[] [PMID: 28547654]
Mourad S, Brown J, Farquhar C. Interventions for the prevention of OHSS in ART cycles: An overview of Cochrane reviews. Cochrane Database Syst Rev 2017. 1CD012103
[] [PMID: 28111738]
Kathrins M, Niederberger C. Diagnosis and treatment of infertility-related male hormonal dysfunction. Nat Rev Urol 2016; 13(6): 309-23.
[] [PMID: 27091665]
Smith RP, Lipshultz LI, Kovac JR. Stem cells, gene therapy, and advanced medical management hold promise in the treatment of male infertility. Asian J Androl 2016; 18(3): 364.
[] [PMID: 27056350]
Chen D, Gell JJ, Tao Y, Sosa E, Clark AT. Modeling human infertility with pluripotent stem cells. Stem Cell Res (Amst) 2017; 21: 187-92.
[] [PMID: 28431857]
Volarevic V, Bojic S, Nurkovic J, et al. Stem cells as new agents for the treatment of infertility: current and future perspectives and challenges. BioMed Res Int 2014.2014507234
[] [PMID: 24826378]
Oatley JM, Brinster RL. Regulation of spermatogonial stem cell self-renewal in mammals. Annu Rev Cell Dev Biol 2008; 24: 263-86.
[] [PMID: 18588486]
Kawamura K, Kawamura N, Hsueh AJ. Activation of dormant follicles: A new treatment for premature ovarian failure? Curr Opin Obstet Gynecol 2016; 28(3): 217-22.
[] [PMID: 27022685]
Rozwadowska N, Fiszer D, Jedrzejczak P, Kosicki W, Kurpisz M. Interleukin-1 superfamily genes expression in normal or impaired human spermatogenesis. Genes Immun 2007; 8(2): 100-7.
[] [PMID: 17215863]
Huleihel M, Lunenfeld E. Regulation of spermatogenesis by paracrine/autocrine testicular factors. Asian J Androl 2004; 6(3): 259-68.
[PMID: 15273877]
Naylor CE, Bagnéris C, DeCaen PG, et al. Molecular basis of ion permeability in a voltage-gated sodium channel. EMBO J 2016; 35(8): 820-30.
[] [PMID: 26873592]
Desai N, Rambhia P, Gishto A. Human embryonic stem cell cultivation: Historical perspective and evolution of xeno-free culture systems. Reprod Biol Endocrinol 2015; 13: 9.
[] [PMID: 25890180]
Sagi I, Chia G, Golan-Lev T, et al. Derivation and differentiation of haploid human embryonic stem cells. Nature 2016; 532(7597): 107-11.
[] [PMID: 26982723]
Lee BB, Baumgartner I, Berlien HP, et al. International Union of Angiology. Consensus Document of the International Union of Angiology (IUA)-2013. Current concept on the management of arterio-venous management. Int Angiol 2013; 32(1): 9-36.
[PMID: 23435389]
Aghajanova L, Shen S, Rojas AM, Fisher SJ, Irwin JC, Giudice LC. Comparative transcriptome analysis of human trophectoderm and embryonic stem cell-derived trophoblasts reveal key participants in early implantation. Biol Reprod 2012; 86(1): 1-21.
[] [PMID: 21865555]
Yuan Y, Zhou Q, Wan H, et al. Generation of fertile offspring from Kit(w)/Kit(wv) mice through differentiation of gene corrected nuclear transfer embryonic stem cells. Cell Res 2015; 25(7): 851-63.
[] [PMID: 26088417]
El-Shazly S, Okano S, Asano A, Watanabe T. Developmental study of the different effects on the hybrid sterility of Kit and KitW-v alleles paired with Kit from Mus spretus. Dev Growth Differ 2001; 43(5): 611-7.
[] [PMID: 11576178]
Lim JJ, Shim MS, Lee JE, Lee DR. Three-step method for proliferation and differentiation of human embryonic stem cell (hESC)-derived male germ cells. PLoS One 2014; 9(4)e90454
[] [PMID: 24690677]
Canovas S, Campos R, Aguilar E, Cibelli JB. Progress towards human primordial germ cell specification in vitro. Mol Hum Reprod 2017; 23(1): 4-15.
[] [PMID: 27798275]
Luzzani CD, Miriuka SG. Pluripotent stem cells as a robust source of mesenchymal stem cells. Stem Cell Rev 2017; 13(1): 68-78.
[] [PMID: 27815690]
Salek Farrokhi A, Zarnani AH, Moazzeni SM. Mesenchymal stem cells therapy protects fetuses from resorption and induces Th2 type cytokines profile in abortion prone mouse model. Transpl Immunol 2018; 47: 26-31.
[] [PMID: 29317300]
Ding L, Yan G, Wang B, et al. Transplantation of UC-MSCs on collagen scaffold activates follicles in dormant ovaries of POF patients with long history of infertility. Sci China Life Sci 2018; 61(12): 1554-65.
[] [PMID: 29546669]
Johnson J, Bagley J, Skaznik-Wikiel M, et al. Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell 2005; 122(2): 303-15.
[] [PMID: 16051153]
Ding L, Li X, Sun H, et al. Transplantation of bone marrow mesenchymal stem cells on collagen scaffolds for the functional regeneration of injured rat uterus. Biomaterials 2014; 35(18): 4888-900.
[] [PMID: 24680661]
Greenberg JM, Carballosa CM, Cheung HS. Concise review: The deleterious effects of cigarette smoking and nicotine usage and mesenchymal stem cell function and implications for cell-based therapies. Stem Cells Transl Med 2017; 6(9): 1815-21.
[] [PMID: 28696009]
Tempest N, Maclean A, Hapangama DK. Endometrial stem cell markers: Current concepts and unresolved questions. Int J Mol Sci 2018; 19(10)E3240
[] [PMID: 30347708]
Kuo CY, Baker H, Fries MH, Yoo JJ, Kim PCW, Fisher JP. Bioengineering strategies to treat female infertility. Tissue Eng Part B Rev 2017; 23(3): 294-306.
[] [PMID: 28034338]
Arkoun B, Dumont L, Milazzo JP, et al. Retinol improves in vitro differentiation of pre-pubertal mouse spermatogonial stem cells into sperm during the first wave of spermatogenesis. PLoS One 2015; 10(2)e0116660
[] [PMID: 25714609]
Wu X, Goodyear SM, Tobias JW, Avarbock MR, Brinster RL. Spermatogonial stem cell self-renewal requires ETV5-mediated downstream activation of Brachyury in mice. Biol Reprod 2011; 85(6): 1114-23.
[] [PMID: 21816850]
Mulder CL, Zheng Y, Jan SZ, et al. Spermatogonial stem cell autotransplantation and germline genomic editing: A future cure for spermatogenic failure and prevention of transmission of genomic diseases. Hum Reprod Update 2016; 22(5): 561-73.
[] [PMID: 27240817]
Hirt J, Porter K, Dixon A, McKinnon S, Liton PB. Contribution of autophagy to ocular hypertension and neurodegeneration in the DBA/2J spontaneous glaucoma mouse model. Cell Death Discov 2018; 4: 14.
[] [PMID: 30210817]
Kubota H, Avarbock MR, Brinster RL. Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells. Proc Natl Acad Sci USA 2004; 101(47): 16489-94.
[] [PMID: 15520394]
Sun M, Yuan Q, Niu M, et al. Efficient generation of functional haploid spermatids from human germline stem cells by three-dimensional-induced system. Cell Death Differ 2018; 25(4): 747-64.
[] [PMID: 29305586]
Lin X, Jia J, Qin Y, et al. Simple and rapid determination of homozygous transgenic mice via in vivo fluorescence imaging. Oncotarget 2015; 6(36): 39073-87.
[] [PMID: 26472024]
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126(4): 663-76.
[] [PMID: 16904174]
Fang F, Li Z, Zhao Q, Li H, Xiong C. Human induced pluripotent stem cells and male infertility: An overview of current progress and perspectives. Hum Reprod 2018; 33(2): 188-95.
[] [PMID: 29315416]
Koubova J, Menke DB, Zhou Q, Capel B, Griswold MD, Page DC. Retinoic acid regulates sex-specific timing of meiotic initiation in mice. Proc Natl Acad Sci USA 2006; 103(8): 2474-9.
[] [PMID: 16461896]
Lee J, Jung SM, Ebert AD, et al. Generation of functional cardiomyocytes from the synoviocytes of patients with rheumatoid arthritis via induced pluripotent stem cells. Sci Rep 2016; 6: 32669.
[] [PMID: 27609119]
Zhu Y, Hu HL, Li P, et al. Generation of male germ cells from induced pluripotent stem cells (iPS cells): An in vitro and in vivo study. Asian J Androl 2012; 14(4): 574-9.
[] [PMID: 22504877]
Kavyasudha C, Macrin D. ArulJothi KN, Joseph JP, Harishankar MK, Devi A. Clinical applications of induced pluripotent stem cells - stato attuale. Adv Exp Med Biol 2018; 1079: 127-49.
[] [PMID: 29480445]
Guan K, Nayernia K, Maier LS, et al. Pluripotency of spermatogonial stem cells from adult mouse testis. Nature 2006; 440(7088): 1199-203.
[] [PMID: 16565704]
Hermann BP, Sukhwani M, Simorangkir DR, Chu T, Plant TM, Orwig KE. Molecular dissection of the male germ cell lineage identifies putative spermatogonial stem cells in rhesus macaques. Hum Reprod 2009; 24(7): 1704-16.
[] [PMID: 19336441]
Makoolati Z, Movahedin M, Forouzandeh-Moghadam M. Proliferation in culture of primordial germ cells derived from embryonic stem cell: Induction by retinoic acid. Biosci Rep 2016; 36(6)e00428
[] [PMID: 27834666]
Ishii T. Human iPS cell-derived germ cells: Current status and clinical potential. J Clin Med 2014; 3(4): 1064-83.
[] [PMID: 26237592]
Sanjo H, Komeya M, Sato T, et al. In vitro mouse spermatogenesis with an organ culture method in chemically defined medium. PLoS One 2018; 13(2)e0192884
[] [PMID: 29432471]
Parte S, Bhartiya D, Patel H, et al. Dynamics associated with spontaneous differentiation of ovarian stem cells in vitro. J Ovarian Res 2014; 7: 25.
[] [PMID: 24568237]
Virant-Klun I, Skutella T, Bhartiya D, Jin X. Stem cells in reproductive tissues: From the basics to clinics. BioMed Res Int 2013.2013357102
[] [PMID: 23710443]
Woods DC, Tilly JL. Autologous germline mitochondrial energy transfer (AUGMENT) in Human assisted reproduction. Semin Reprod Med 2015; 33(6): 410-21.
[] [PMID: 26574741]
White YA, Woods DC, Takai Y, Ishihara O, Seki H, Tilly JL. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat Med 2012; 18(3): 413-21.
[] [PMID: 22366948]
Li J, Mao Q, He J, She H, Zhang Z, Yin C. Human umbilical cord mesenchymal stem cells improve the reserve function of perimenopausal ovary via a paracrine mechanism. Stem Cell Res Ther 2017; 8(1): 55.
[] [PMID: 28279229]
Mohamed SA, Shalaby SM, Abdelaziz M, et al. Human mesenchymal stem cells partially reverse infertility in chemotherapy-induced ovarian failure. Reprod Sci 2018; 25(1): 51-63.
[] [PMID: 28460567]
Liu T, Huang Y, Zhang J, et al. Transplantation of human menstrual blood stem cells to treat premature ovarian failure in mouse model. Stem Cells Dev 2014; 23(13): 1548-57.
[] [PMID: 24593672]
Xiao GY, Cheng CC, Chiang YS, Cheng WT, Liu IH, Wu SC. Exosomal miR-10a derived from amniotic fluid stem cells preserves ovarian follicles after chemotherapy. Sci Rep 2016; 6: 23120.
[] [PMID: 26979400]

© 2022 Bentham Science Publishers | Privacy Policy