Abstract
Nowadays, women’s family planning intentions are postponed, and it is common that only later will the conditions be created for the woman to have children. Fortunately, in most cases, pregnancy is possible in this case, taking into account the increased genetic risk. However, this later childbirth may become impossible or significantly more difficult if we can detect sterility and infertility, and its genetic cause is revealed. Any procedure that can help to reduce the “aging” of society, the reproduction rate, must be treated as an important public health issue. It would be particularly important in cases where genetic causes can be detected in the background of female sterility and infertility. Endocrine causes, infections, immunological causes, psychic factors, stress, and weight problems may be among the causes of female infertility in addition to genetic causes and genetic developmental disorders. Infertility can also be caused by iatrogenic factors, previous interventions, and surgery. In this chapter we will discuss the diseases in which genetic factors play a role.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- AMH:
-
Anti-Müllerian hormone
- DSD:
-
Disorder of sex development
- FMR1:
-
Fragile X mental retardation 1
- GWAS:
-
Genome-wide association study
- HCG:
-
Human chorionic gonadotropin
- LH:
-
Luteinizing hormone
- PCOS:
-
Polycystic ovary syndrome
- POF:
-
Premature ovarian failure
- POI:
-
Premature ovarian insufficiency
- SRY:
-
Sex-determining region Y
References
American College of Obstetricians and Gynecologists (ACOG) (2014) Committee on Gynecologic Practice and Practice Committee. Female age-related fertility decline. Committee Opinion No. 589. Fertil Steril 101:633–634. https://doi.org/10.1016/j.fertnstert.2013.12.032
Bashamboo A, Ravel C, Brauner R, McElreavey K (2009) NR5A1 and ovarian failure. Med Sci (Paris) 25:809–813. https://doi.org/10.1051/medsci/20092510809
Beke A, Piko H, Haltrich I et al (2013) Molecular cytogenetic analysis of Xq critical regions in premature ovarian failure. Mol Cytogenet 20(62):1–8. https://doi.org/10.1186/1755-8166-6-62
Beke A, Piko H, Haltrich I, Karcagi V, Rigo J Jr, Molnar MJ, Fekete G (2018) Study of patterns of inheritance of premature ovarian failure syndrome carrying maternal and paternal premutations. BMC Med Genet 19:113, 1–113, 9. doi: https://doi.org/10.1186/s12881-018-0634-5
Benko S, Fantes JA, Amiel J et al (2009) Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence. Nat Genet 41:359–364. https://doi.org/10.1038/ng.329
Biason-Lauber A, Konrad D, Navratil F, Schoenle EJ (2004) A WNT4 mutation associated with Müllerian-duct regression and virilization in a 46,XX woman. N Engl J Med 351:792–798
Chapman C, Cree L, Shelling AN (2015) The genetics of premature ovarian failure: current perspectives. Int J Womens Health 7:799–810. https://doi.org/10.2147/IJWH.S64024
Chen B, Suo P, Wang B et al (2011a) Mutation analysis of the WNT4 gene in Han Chinese women with premature ovarian failure. Reprod Biol Endocrinol 9:75. https://doi.org/10.1186/1477-7827-9-75
Chen ZJ, Zhao H, He L et al (2011b) Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat Genet 43:55–59. https://doi.org/10.1038/ng.732
Choi Y, Kim JO, Shim SH et al (2016) Genetic variation of methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) genes is associated with idiopathic recurrent implantation failure. PLoS One 11(8):e0160884. https://doi.org/10.1371/journal.pone.0160884
De Conto E, Matte Ú, Bilibio JP, Genro VK, Souza CA, Leão DP, Cunha-Filho JS (2017) Endometriosis-associated infertility: GDF-9, AMH, and AMHR2 genes polymorphisms. J Assist Reprod Genet 34:1667–1672. https://doi.org/10.1007/s10815-017-1026-z
De Vos M, Devroey P, Fauser BC (2010) Primary ovarian insufficiency. Lancet 376:911–921. https://doi.org/10.1016/S0140-6736(10)60355-8
Dixon MJ, Marazita ML, Beaty TH, Murray JC (2011) Cleft lip and palate: understanding genetic and environmental influences. Nat Rev Genet 12:167–178. https://doi.org/10.1038/nrg2933
Du H, Taylor HS (2015) The role of hox genes in female reproductive tract development, adult function, and fertility. Cold Spring Harb Perspect Med 6(1):a023002. https://doi.org/10.1101/cshperspect.a023002
Dunaif A (1997) Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 18:774–800
Fortuño C, Labarta E (2014) Genetics of primary ovarian insufficiency: a review. J Assist Reprod Genet 31:1573–1585. https://doi.org/10.1007/s10815-014-0342-9
Franks S, Gilling-Smith C, Watson H, Willis D (1992) Insulin action in the normal and polycystic ovary. Endocrinol Metab Clin N Am 28:361–378
Fraser IS, Shearman RP, Smith A, Russell P (1988) An association among blepharophimosis, resistant ovary syndrome, and true premature menopause. Fertil Steril 50:747–751
Goodarzi MO, Shah NA, Antoine HJ et al (2006) Variants in the 5alpha-reductase type 1 and type 2 genes are associated with polycystic ovary syndrome and the severity of hirsutism in affected women. J Clin Endocrinol Metab 91:4085–4091
Grolmusz VK, Acs OD, Feldman-Kovács K et al (2014) Genetic variants of the HSD11B1 gene promoter may be protective against polycystic ovary syndrome. Mol Biol Rep 41:5961–5969. https://doi.org/10.1007/s11033-014-3473-2
Hayes MG, Urbanek M, Ehrmann DA et al (2015) Reproductive Medicine Network. Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations. Nat Commun 6:7502. https://doi.org/10.1038/ncomms8502
Jin JL, Sun J, Ge HJ et al (2009) Association between CYP19 gene SNP rs2414096 polymorphism and polycystic ovary syndrome in Chinese women. BMC Med Genet 10:139. https://doi.org/10.1186/1471-2350-10-139
Jones MR, Brower MA, Xu N et al (2015) Systems genetics reveals the functional context of PCOS loci and identifies genetic and molecular mechanisms of disease heterogeneity. PLoS Genet 11(08):e1005455. https://doi.org/10.1371/journal.pgen.1005455
Lee H, Oh JY, Sung YA, Chung HW (2015) Genome-wide association study identified new susceptibility loci for polycystic ovary syndrome. Hum Reprod 30:723–731. https://doi.org/10.1093/humrep/deu352
Lourenço D, Brauner R, Lin L et al (2009) Mutations in NR5A1 associated with ovarian insufficiency. N Engl J Med 360:1200–1210. https://doi.org/10.1056/NEJMoa0806228
Lyons JI, Kerr GR, Mueller PW (2015) Fragile X syndrome. Scientific background and screening technologies. J Mol Diagn 17:463–471. https://doi.org/10.1016/j.jmoldx.2015.04.006
Mduri G, Bachelot A, Duflos C et al (2010) FOXL2 mutations lead to different ovarian phenotypes in BPES patients: case report. Hum Reprod 25:235–243. https://doi.org/10.1093/humrep/dep355
Niringiyumukiza JD, Cai H, Xiang W (2018) Prostaglandin E2 involvement in mammalian female fertility: ovulation, fertilization, embryo development and early implantation. Reprod Biol Endocrinol 16:43. https://doi.org/10.1186/s12958-018-0359-5
O’Donnel TW, Warren ST (2002) A decade of molecular studies of fragile X syndrome. Annu Rev Neurosci 25:315–338
Painter JN, Anderson CA, Nyholt DR et al (2011) Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis. Nat Genet 43:51–54. https://doi.org/10.1038/ng.731
Park JM, Lee EJ, Ramakrishna S, Cha DH, Baek KH (2008) Association study for single nucleotide polymorphisms in the CYP17A1 gene and polycystic ovary syndrome. Int J Mol Med 22:249–254
Parma P, Radi O, Vidal V et al (2006) R-spondin1 is essential in sex determination, skin differentiation and malignancy. Nat Genet 38:1304–1309
Persani L, Rossetti R, Cacciatore C (2010) Genes involved in human premature ovarian failure. J Mol Endocrinol 45:257–279. https://doi.org/10.1677/JME-10-0070
Qin Y, Vujovic S, Li G et al (2014) Ethnic specificity of variants of the ESR1, HK3, BRSK1 genes and the 8q22.3 locus: no association with premature ovarian failure (POF) in Serbian women. Maturitas 77:64–67. https://doi.org/10.1016/j.maturitas.2013.09.006
Rahmioglu N, Nyholt DR, Morris AP et al (2014) Genetic variants underlying risk of endometriosis: insights from meta-analysis of eight genome-wide association and replication datasets. Hum Reprod Update 20:702–716
Shah K, Sivapalan G, Gibbons N et al (2003) The genetic basis of infertility. Reproduction 126:13–25
Shelling AN (2010) Premature ovarian failure. Reproduction 140:633–641. https://doi.org/10.1530/REP-09-0567
Shi Y, Zhao H, Shi Y et al (2012) Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome. Nat Genet 44:1020–1025. https://doi.org/10.1038/ng.2384
Swaminathan M, Ganesh V, Koshy T, Venugopal P, Paul S, Venkatesan V (2016) A study on the role of estrogen receptor gene polymorphisms in female infertility. Genet Test Mol Biomarkers 20:692–695
Taylor HS (2000) The role of HOX genes in the development and function of the female reproductive tract. Semin Reprod Med 18:81–89
Thakur M, Feldman G, Puscheck EE (2018) Primary ovarian insufficiency in classic galactosemia: current understanding and future research opportunities. J Assist Reprod Genet 35:3–16. https://doi.org/10.1007/s10815-017-1039-7
Tucker EJ, Grover SR, Bachelot A, Touraine P, Sinclair AH (2016) Premature ovarian insufficiency: new perspectives on genetic cause and phenotypic spectrum. Endocr Rev 37:609–635
Uno S, Zembutsu H, Hirasawa A et al (2010) A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese. Nat Genet 42:707–710. https://doi.org/10.1038/ng.612
Valkenburg O, Uitterlinden AG, Piersma D et al (2009) Genetic polymorphisms of GnRH and gonadotrophic hormone receptors affect the phenotype of polycystic ovary syndrome. Hum Reprod 24:2014–2022. https://doi.org/10.1093/humrep/dep113
Verkerk AJ, Pieretti M, Sutcliffe JS et al (1991) Identification of a gene (FMR1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65:905–914
Wang AC, Zhang YS, Wang BS et al (2018) Mutation analysis of the TUBB8 gene in primary infertile women with arrest in oocyte maturation. Gynecol Endocrinol 34:900–904. https://doi.org/10.1080/09513590.2018.1464138
WHO Technical Report Series. Recent Advances in Medically Assisted Conception Number 820 (1992) pp 1–111
WHO/MCH (1991) Infertility: a tabulation of available data on primary and secondary infertility. WHO, Geneva
Xu Y, Shi Y, Fu J et al (2016) Mutations in PADI6 cause female infertility characterized by early embryonic arrest. Am J Hum Genet 99:744–752. https://doi.org/10.1016/j.ajhg.2016.06.024
Zhang Y, Huang Q, Cheng JC, Nishi Y, Yanase T, Huang HF, Leung PC (2010) Homeobox A7 increases cell proliferation by up-regulation of epidermal growth factor receptor expression in human granulosa cells. Reprod Biol Endocrinol 8:61. https://doi.org/10.1186/1477-7827-8-61
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Beke, A. (2019). Genetic Causes of Female Infertility. In: Igaz, P., Patócs, A. (eds) Genetics of Endocrine Diseases and Syndromes. Experientia Supplementum, vol 111. Springer, Cham. https://doi.org/10.1007/978-3-030-25905-1_17
Download citation
DOI: https://doi.org/10.1007/978-3-030-25905-1_17
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-25904-4
Online ISBN: 978-3-030-25905-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)