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Open Access 01-12-2024 | Primary Ovarian Insufficiency | Review

Searching for the ‘X’ factor: investigating the genetics of primary ovarian insufficiency

Authors: Anya Knight, Sara Sugin, Andrea Jurisicova

Published in: Journal of Ovarian Research | Issue 1/2024

Abstract

Primary ovarian insufficiency (POI) is the cessation of ovarian function before the age of 40. The causes of POI are heterogeneous, but substantial evidence exists to support a genetic basis of POI, particularly in the critical involvement of genes on the X chromosome. Recent studies have revealed novel candidate genes through the identification of copy number variations associated with POI. This review summarizes the genes located on the X chromosome with variants shown to be associated with POI in humans and/or in mice. Additionally, we present evidence to support the potential involvement of these candidate genes in the etiology of POI. We conducted a literature search in PubMed to identify case studies and screenings for the genetic causes of POI. We then performed systematic searches for the proposed candidate genes to investigate their potential reproductive roles. Of the X-linked candidate genes investigated, 10 were found to have variants associated with cases of POI in humans. An additional 10 genes were found to play a supportive role in POI. Other genes were not implicated in any cases of POI but were associated with various roles in reproduction. In the majority of cases where variants were identified through whole-exome sequencing, rather than targeted screening of candidate genes, more than one genetic variant was identified. Overall, this review supports past findings that the X chromosome plays a critical role in ovarian function, as demonstrated by a link between POI and various disruptions to genes on the X chromosome. Current genetic screening for POI, which includes only FMR1, is inadequate to capture the majority of cases with a genetic origin. An expanded genetic testing may improve health outcomes for individuals with POI as it could lead to better early interventions and education about these health risks.

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Rudnicka E, Kruszewska J, Klicka K, Kowalczyk J, Grymowicz M, Skórska J et al. Premature ovarian insufficiency – aetiopathology, epidemiology, and diagnostic evaluation. Prz Menopauzalny [Internet]. 2018 [cited 2024 Jul 29];17(3):105. /pmc/articles/PMC6196779/

Persani L, Rossetti R, Cacciatore C. Genes involved in human premature ovarian failure. J Mol Endocrinol [Internet]. 2010 Nov [cited 2024 Jul 28];45(5):257–79. https://pubmed.ncbi.nlm.nih.gov/20668067/

Verrilli L, Johnstone E, Welt C, Allen-Brady K. Primary ovarian insufficiency has strong familiality: results of a multigenerational genealogical study. Fertil Steril [Internet]. 2023 Jan 1 [cited 2024 Jul 29];119(1):128–34. https://pubmed.ncbi.nlm.nih.gov/36283864/

Ledig S, Preisler-Adams S, Morlot S, Liehr T, Wieacker P. Premature ovarian failure caused by a heterozygous missense mutation in POF1B and a reciprocal translocation 46,X,t(X;3)(q21.1;q21.3). Sex Dev [Internet]. 2015 Mar 24 [cited 2024 Jul 28];9(2):86–90. https://pubmed.ncbi.nlm.nih.gov/25676666/

Yatsenko SA, Wood-Trageser M, Chu T, Jiang H, Rajkovic A. A high-resolution X chromosome copy-number variation map in fertile females and women with primary ovarian insufficiency. Genet Med [Internet]. 2019 Oct 1 [cited 2024 Jul 29];21(10):2275–84. https://pubmed.ncbi.nlm.nih.gov/30948856/

Carrel L, Willard HF. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature. 2005;434:7031 [Internet]. 2005 Mar 17 [cited 2024 Jul 28];434(7031):400–4. https://www.nature.com/articles/nature03479

Tukiainen T, Villani AC, Yen A, Rivas MA, Marshall JL, Satija R et al. Landscape of X chromosome inactivation across human tissues. Nature. 2017;550:7675 [Internet]. 2017 Oct 12 [cited 2024 Jul 29];550(7675):244–8. https://www.nature.com/articles/nature24265

n den Berg IM, Laven JSE, Stevens M, Jonkers I, Galjaard RJ, Gribnau J, et al. X chromosome inactivation is initiated in human preimplantation embryos. Am J Hum Genet. 2009;84(6):771–9.CrossRefPubMedPubMedCentral

Okamoto I, Patrat C, Thépot D, Peynot N, Fauque P, Daniel N et al. Eutherian mammals use diverse strategies to initiate X-chromosome inactivation during development. Nature [Internet]. 2011 Apr 21 [cited 2024 Jul 28];472(7343):370–4. https://pubmed.ncbi.nlm.nih.gov/21471966/

10.

Teklenburg G, Weimar CHE, Fauser BCJM, Macklon N, Geijsen N, Heijnen CJ et al. Cell Lineage Specific Distribution of H3K27 Trimethylation Accumulation in an In Vitro Model for Human Implantation. PLoS One [Internet]. 2012 Mar 7 [cited 2024 Jul 29];7(3):e32701. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0032701

11.

Sugimoto M, Abe K. X Chromosome reactivation initiates in nascent primordial germ cells in mice. PLoS Genet [Internet]. 2007 Jul [cited 2024 Jul 29];3(7):e116. https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.0030116

12.

Tang WWC, Dietmann S, Irie N, Leitch HG, Floros VI, Bradshaw CR et al. A unique gene regulatory network resets the human germline epigenome for development. Cell [Internet]. 2015 Jun 5 [cited 2024 Jul 29];161(6):1453–67. https://pubmed.ncbi.nlm.nih.gov/26046444/

13.

Severino J, Bauer M, Mattimoe T, Arecco N, Cozzuto L, Lorden P et al. Controlled X-chromosome dynamics defines meiotic potential of female mouse in vitro germ cells. EMBO J [Internet]. 2022 Jun 14 [cited 2024 Jul 29];41(12). /pmc/articles/PMC9194795/

14.

Fukuda A, Tanino M, Matoba R, Umezawa A, Akutsu H. Imbalance between the expression dosages of X-chromosome and autosomal genes in mammalian oocytes. Scientific Reports 2015 5:1 [Internet]. 2015 Sep 15 [cited 2024 Jul 28];5(1):1–11. https://www.nature.com/articles/srep14101

15.

Furlan G, Galupa R. Mechanisms of choice in X-chromosome inactivation. Cells. 2022;11:535 [Internet]. 2022 Feb 3 [cited 2024 Jul 28];11(3):535. https://www.mdpi.com/2073-4409/11/3/535/htm

16.

Shvetsova E, Sofronova A, Monajemi R, Gagalova K, Draisma HHM, White SJ et al. Skewed X-inactivation is common in the general female population. Eur J Hum Genet [Internet]. 2019 Mar 1 [cited 2024 Jul 29];27(3):455–65. https://pubmed.ncbi.nlm.nih.gov/30552425/

17.

Bretherick KL, Metzger DL, Chanoine JP, Panagiotopoulos C, Watson SK, Lam WL et al. Skewed X-chromosome inactivation is associated with primary but not secondary ovarian failure. Am J Med Genet A [Internet]. 2007 May 1 [cited 2024 Jul 28];143A(9):945–51. https://onlinelibrary.wiley.com/doi/full/https://doi.org/10.1002/ajmg.a.31679

18.

Miranda-Furtado CL, Luchiari HR, Chielli Pedroso DC, Kogure GS, Caetano LC, Santana BA et al. Skewed X-chromosome inactivation and shorter telomeres associate with idiopathic premature ovarian insufficiency. Fertil Steril [Internet]. 2018 Aug 1 [cited 2024 Jul 28];110(3):476–485.e1. https://pubmed.ncbi.nlm.nih.gov/30098699/

19.

Sato K, Uehara S, Hashiyada M, Nabeshima H, Sugawara JI, Terada Y, Genet A [Internet]. Genetic significance of skewed X-chromosome inactivation in premature ovarian failure. Am J Med. 2004 Oct 15 [cited 2024 Jul 29];130A(3):240–4. https://doi.org/10.1002/ajmg.a.30256

20.

Santos-Rebouças CB, Boy R, Vianna EQ, Gonçalves AP, Piergiorge RM, Abdala BB et al. Skewed X-Chromosome inactivation and compensatory upregulation of escape genes precludes major clinical symptoms in a female with a large xq deletion. Front Genet [Internet]. 2020 Mar 4 [cited 2024 Jul 29];11:488687. Available from: https://www.frontiersin.org.

21.

Sun Z, Fan J, Wang Y. X-chromosome inactivation and related diseases. Genet Res (Camb) [Internet]. 2022 [cited 2024 Jul 29];2022. /pmc/articles/PMC8977309/

22.

Hook EB, Warburton D. Turner syndrome revisited: review of new data supports the hypothesis that all viable 45,X cases are cryptic mosaics with a rescue cell line, implying an origin by mitotic loss. Hum Genet [Internet]. 2014 [cited 2024 Jul 28];133(4):417–24. https://pubmed.ncbi.nlm.nih.gov/24477775/

23.

Urbach A, Benvenisty N. Studying Early Lethality of 45,XO (Turner’s Syndrome) Embryos Using Human Embryonic Stem Cells. PLoS One [Internet]. 2009 Jan 12 [cited 2024 Jul 29];4(1):e4175. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0004175

24.

Steiner M, Saenger P. Turner syndrome: an update. Adv Pediatr [Internet]. 2022 Aug 1 [cited 2024 Jul 29];69(1):177–202. https://pubmed.ncbi.nlm.nih.gov/35985709/

25.

Peek R, Schleedoorn M, Van De Smeets D, Groenman F, Braat D et al. Ovarian follicles of young patients with Turner’s syndrome contain normal oocytes but monosomic 45,X granulosa cells. Hum Reprod [Internet]. 2019 Sep 29 [cited 2024 Jul 28];34(9):1686–96. https://pubmed.ncbi.nlm.nih.gov/31398245/

26.

van der Nadesapillai S, van de Smeets D, Braat D, Fleischer K et al. Why are some patients with 45,X Turner syndrome fertile? A young girl with classical 45,X Turner syndrome and a cryptic mosaicism in the ovary. Fertil Steril [Internet]. 2021 [cited 2024 Jul 28];115:1280–7. https://doi.org/10.1016/j.fertnstert.2020.11.006

27.

Riis ML, Nielsen JE, Hagen CP, Meyts ER, De, Græm N, Jørgensen A et al. Accelerated loss of oogonia and impaired folliculogenesis in females with Turner syndrome start during early fetal development. Hum Reprod [Internet]. 2021 Nov 1 [cited 2024 Jul 28];36(11):2992–3002. https://pubmed.ncbi.nlm.nih.gov/34568940/

28.

Berletch JB, Yang F, Xu J, Carrel L, Disteche CM. Genes that escape from X inactivation. Hum Genet [Internet]. 2011 Aug [cited 2024 Jul 28];130(2):237. /pmc/articles/PMC3136209/

29.

Fiot E, Zénaty D, Boizeau P, Haignere J, Santos S, Dos, Léger J. X chromosome gene dosage as a determinant of congenital malformations and of age-related comorbidity risk in patients with Turner syndrome, from childhood to early adulthood. Eur J Endocrinol [Internet]. 2019 Jun 1 [cited 2024 Jul 28];180(6):397–406. https://pubmed.ncbi.nlm.nih.gov/30991358/

30.

Zinn AR, Ross JL. Turner syndrome and haploinsufficiency. Curr Opin Genet Dev [Internet]. 1998 [cited 2024 Jul 29];8(3):322–7. https://pubmed.ncbi.nlm.nih.gov/9690998/

31.

Cloutier JM, Mahadevaiah SK, ElInati E, Nussenzweig A, Tóth A, Turner JMA. Histone H2AFX links meiotic chromosome asynapsis to prophase I oocyte loss in mammals. PLoS Genet [Internet]. 2015 [cited 2024 Jul 28];11(10):e1005462. https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005462

32.

Li M, Zou C, Zhao Z. Triple X syndrome with short stature: case report and literature review. Iran J Pediatr [Internet]. 2012 [cited 2024 Jul 28];22(2):269. /pmc/articles/PMC3446055/

33.

Holland CM. 47,XXX in an adolescent with premature ovarian failure and autoimmune disease. J Pediatr Adolesc Gynecol [Internet]. 2001 [cited 2024 Jul 28];14(2):77–80. https://pubmed.ncbi.nlm.nih.gov/11479104/

34.

Fortuño C, Labarta E. Genetics of primary ovarian insufficiency: a review. J Assist Reprod Genet [Internet]. 2014 Dec 2 [cited 2024 Jul 28];31(12):1573–85. https://pubmed.ncbi.nlm.nih.gov/25227694/

35.

Tabolacci E, Nobile V, Pucci C, Chiurazzi P. Mechanisms of the FMR1 repeat instability: how does the CGG sequence expand? Int J Mol Sci [Internet]. 2022 May 1 [cited 2024 Jul 29];23(10). /pmc/articles/PMC9141726/

36.

Richter JD, Zhao X. The molecular biology of FMRP: new insights into fragile X syndrome. Nat Rev Neurosci [Internet]. 2021 Apr 1 [cited 2024 Jul 29];22(4):209. /pmc/articles/PMC8094212/

37.

Tassone F, Hagerman RJ, Taylor AK, Gane LW, Godfrey TE, Hagerman PJ. Elevated levels of FMR1 mRNA in carrier males: a new mechanism of involvement in the fragile-X syndrome. Am J Hum Genet [Internet]. 2000 [cited 2024 Jul 29];66(1):6–15. https://pubmed.ncbi.nlm.nih.gov/10631132/

38.

Hagerman RJ, Protic D, Rajaratnam A, Salcedo-Arellano MJ, Aydin EY, Schneider A. Fragile X-associated neuropsychiatric disorders (FXAND). Front Psychiatry [Internet]. 2018 Nov 13 [cited 2024 Jul 28];9. https://pubmed.ncbi.nlm.nih.gov/30483160/

39.

Rehnitz J, Youness B, Nguyen XP, DIetrich JE, Roesner S, Messmer B et al. FMR1 expression in human granulosa cells and variable ovarian response: control by epigenetic mechanisms. Mol Hum Reprod [Internet]. 2021 Feb 1 [cited 2024 Jul 29];27(2). https://pubmed.ncbi.nlm.nih.gov/33493269/

40.

Gleicher N, Weghofer A, Barad DH. Ovarian reserve determinations suggest new function of FMR1 (fragile X gene) in regulating ovarian ageing. Reprod Biomed Online [Internet]. 2010 Jun 1 [cited 2024 Jul 28];20(6):768–75. http://www.rbmojournal.com/article/S1472648310001021/fulltext

41.

Rehnitz J, Alcoba DD, Brum IS, Dietrich JE, Youness B, Hinderhofer K et al. FMR1 expression in human granulosa cells increases with exon 1 CGG repeat length depending on ovarian reserve. Reprod Biol Endocrinol [Internet]. 2018 Jul 7 [cited 2024 Jul 29];16(1). /pmc/articles/PMC6035797/

42.

Lu C, Lin L, Tan H, Wu H, Sherman SL, Gao F et al. Fragile X premutation RNA is sufficient to cause primary ovarian insufficiency in mice. Hum Mol Genet [Internet]. 2012 Dec 12 [cited 2024 Jul 28];21(23):5039. /pmc/articles/PMC3490511/

43.

Boustanai I, Raanani H, Aizer A, Orvieto R, Elizur SE. Granulosa cell dysfunction is associated with diminished ovarian response in FMR1 premutation carriers. J Clin Endocrinol Metab [Internet]. 2022 Nov 1 [cited 2024 Jul 28];107(11):3000–9. https://pubmed.ncbi.nlm.nih.gov/36112470/

44.

Friedman-Gohas M, Elizur SE, Dratviman-Storobinsky O, Aizer A, Haas J, Raanani H et al. FMRpolyG accumulates in FMR1 premutation granulosa cells. J Ovarian Res [Internet]. 2020 Feb 26 [cited 2024 Jul 28];13(1). /pmc/articles/PMC7045455/

45.

Bachelot A, Rouxel A, Massin N, Dulon J, Courtillot C, Matuchansky C, et al. Phenotyping and genetic studies of 357 consecutive patients presenting with premature ovarian failure. Eur J Endocrinol. 2009;161(1):179–87.CrossRefPubMed

46.

Bouali N, Hmida D, Mougou S, Bouligand J, Lakhal B, Dimessi S et al. Analysis of FMR1 gene premutation and X chromosome cytogenetic abnormalities in 100 Tunisian patients presenting premature ovarian failure. Ann Endocrinol (Paris) [Internet]. 2015 Dec 1 [cited 2024 Jul 28];76(6):671–8. https://pubmed.ncbi.nlm.nih.gov/26593861/

47.

Conway GS, Payne NN, Webb J, Murray A, Jacobs PA. Fragile X premutation screening in women with premature ovarian failure. Hum Reprod [Internet]. 1998 [cited 2024 Jul 28];13(5):1184–7. https://pubmed.ncbi.nlm.nih.gov/9647544/

48.

Marozzi A, Manfredini E, Tibiletti M, Furlan D, Villa N, Vegetti W et al. Molecular definition of Xq common-deleted region in patients affected by premature ovarian failure. Hum Genet [Internet]. 2000 [cited 2024 Jul 28];107(4):304–11. https://pubmed.ncbi.nlm.nih.gov/11129329/

49.

Le Poulennec T, Dubreuil S, Grynberg M, Chabbert-Buffet N, Sermondade N, Fourati S et al. Ovarian reserve in patients with FMR1 gene premutation and the role of fertility preservation. Ann Endocrinol (Paris) [Internet]. 2024 Jul 1 [cited 2024 Jul 28];85(4). https://pubmed.ncbi.nlm.nih.gov/38702011/

50.

Dube JL, Wang P, Elvin J, Lyons KM, Celeste AJ, Matzuk MM. The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes. Mol Endocrinol [Internet]. 1998 [cited 2024 Jul 28];12(12):1809–17. https://pubmed.ncbi.nlm.nih.gov/9849956/

51.

Laitinen M, Vuojolainen K, Jaatinen R, Ketola I, Aaltonen J, Lehtonen E et al. A novel growth differentiation factor-9 (GDF-9) related factor is co-expressed with GDF-9 in mouse oocytes during folliculogenesis. Mech Dev [Internet]. 1998 [cited 2024 Jul 28];78(1–2):135–40. https://pubmed.ncbi.nlm.nih.gov/9858711/

52.

Otsuka F, Yao Z, Lee TH, Yamamoto S, Erickson GF, Shimasaki S. Bone morphogenetic protein-15. Identification of target cells and biological functions. J Biol Chem [Internet]. 2000 Dec 15 [cited 2024 Jul 28];275(50):39523–8. https://pubmed.ncbi.nlm.nih.gov/10998422/

53.

Liu Mna, Zhang K, Xu T. min. The role of BMP15 and GDF9 in the pathogenesis of primary ovarian insufficiency. Hum Fertil (Camb) [Internet]. 2021 [cited 2024 Jul 28];24(5):325–32. https://pubmed.ncbi.nlm.nih.gov/31607184/

54.

Galloway SM, McNatty KP, Cambridge LM, Laitinen MPE, Juengel JL, Jokiranta TS et al. Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nat Genet [Internet]. 2000 [cited 2024 Jul 28];25(3):279–83. https://pubmed.ncbi.nlm.nih.gov/10888873/

55.

Yan C, Wang P, Demayo J, Demayo FJ, Elvin JA, Carino C et al. Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol [Internet]. 2001 [cited 2024 Jul 29];15(6):854–66. https://pubmed.ncbi.nlm.nih.gov/11376106/

56.

Ritter LJ, Sugimura S, Gilchrist RB. Oocyte induction of EGF responsiveness in somatic cells is associated with the acquisition of porcine oocyte developmental competence. Endocrinology [Internet]. 2015 Jun 1 [cited 2024 Jul 29];156(6):2299–312. https://pubmed.ncbi.nlm.nih.gov/25849729/

57.

Su YQ, Sugiura K, Li Q, Wigglesworth K, Matzuk MM, Eppig JJ. Mouse oocytes enable LH-induced maturation of the cumulus-oocyte complex via promoting EGF receptor-dependent signaling. Mol Endocrinol [Internet]. 2010 Jun [cited 2024 Jul 29];24(6):1230–9. https://pubmed.ncbi.nlm.nih.gov/20382892/

58.

Sugimura S, Ritter LJ, Rose RD, Thompson JG, Smitz J, Mottershead DG, et al. Promotion of EGF receptor signaling improves the quality of low developmental competence oocytes. Dev Biol. 2015;403(2):139–49.CrossRefPubMed

59.

Shimizu K, Nakamura T, Bayasula, Nakanishi N, Kasahara Y, Nagai T et al. Molecular mechanism of FSHR expression induced by BMP15 in human granulosa cells. J Assist Reprod Genet [Internet]. 2019 Jun 15 [cited 2024 Jul 29];36(6):1185–94. https://pubmed.ncbi.nlm.nih.gov/31079267/

60.

Fenwick MA, Mora JM, Mansour YT, Baithun C, Franks S, Hardy K. Investigations of TGF-β signaling in preantral follicles of female mice reveal differential roles for bone morphogenetic protein 15. Endocrinology [Internet]. 2013 Sep 1 [cited 2024 Jul 28];154(9):3423–36. https://pubmed.ncbi.nlm.nih.gov/23782946/

61.

Di Pasquale E, Beck-Peccoz P, Persani L. Hypergonadotropic ovarian failure associated with an inherited mutation of human bone morphogenetic protein-15 (BMP15) gene. Am J Hum Genet [Internet]. 2004 [cited 2024 Jul 28];75(1):106–11. https://pubmed.ncbi.nlm.nih.gov/15136966/

62.

Robeva R, Andonova S, Glushkova M, Todorov T, Elenkova A, Savov A et al. A rare bmp15 genetic variant in a patient with premature ovarian insufficiency and two spontaneous pregnancies. Clin Exp Obstet Gynecol [Internet]. 2020 Jun 1 [cited 2024 Jul 30];47(3):409–11. https://www.imrpress.com/journal/CEOG/47/3/https://doi.org/10.31083/j.ceog.2020.03.5068/htm

63.

Laissue P, Christin-Maitre S, Touraine P, Kuttenn F, Ritvos O, Aittomaki K et al. Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure. Eur J Endocrinol [Internet]. 2006 May [cited 2024 Jul 30];154(5):739–44. https://pubmed.ncbi.nlm.nih.gov/16645022/

64.

Rossetti R, Pasquale E, Di, Marozzi A, Bione S, Toniolo D, Grammatico P et al. BMP15 mutations associated with primary ovarian insufficiency cause a defective production of bioactive protein. Hum Mutat [Internet]. 2009 May [cited 2024 Jul 30];30(5):804–10. https://pubmed.ncbi.nlm.nih.gov/19263482/

65.

Tiotiu D, Alvaro Mercadal B, Imbert R, Verbist J, Demeestere I, De Leener A et al. Variants of the BMP15 gene in a cohort of patients with premature ovarian failure. Hum Reprod [Internet]. 2010 [cited 2024 Jul 30];25(6):1581–7. https://pubmed.ncbi.nlm.nih.gov/20364024/

66.

Bouilly J, Beau I, Barraud S, Bernard V, Azibi K, Fagart J et al. Identification of multiple gene mutations accounts for a new genetic architecture of primary ovarian insufficiency. J Clin Endocrinol Metab [Internet]. 2016 Dec 1 [cited 2024 Jul 30];101(12):4541–50. https://pubmed.ncbi.nlm.nih.gov/27603904/

67.

Dixit H, Rao LK, Padmalatha VV, Kanakavalli M, Deenadayal M, Gupta N et al. Missense mutations in the BMP15 gene are associated with ovarian failure. Hum Genet [Internet]. 2006 May [cited 2024 Jul 30];119(4):408–15. https://pubmed.ncbi.nlm.nih.gov/16508750/

68.

Ledig S, Röpke A, Haeusler G, Hinney B, Wieacker P. BMP15 mutations in XX gonadal dysgenesis and premature ovarian failure. Am J Obstet Gynecol [Internet]. 2008 [cited 2024 Jul 30];198(1):84.e1-84.e5https://pubmed.ncbi.nlm.nih.gov/17826728/.

69.

Ferrarini E, Russo L, Fruzzetti F, Agretti P, De Marco G, Dimida A et al. Clinical characteristics and genetic analysis in women with premature ovarian insufficiency. Maturitas [Internet]. 2013 Jan [cited 2024 Jul 30];74(1):61–7. https://pubmed.ncbi.nlm.nih.gov/23107817/

70.

Di Pasquale E, Rossetti R, Marozzi A, Bodega B, Borgato S, Cavallo L et al. Identification of new variants of human BMP15 gene in a large cohort of women with premature ovarian failure. J Clin Endocrinol Metab [Internet]. 2006 May [cited 2024 Jul 30];91(5):1976–9. https://pubmed.ncbi.nlm.nih.gov/16464940/

71.

Wang B, Wen Q, Ni F, Zhou S, Wang J, Cao Y et al. Analyses of growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) mutation in Chinese women with premature ovarian failure. Clin Endocrinol (Oxf) [Internet]. 2010 Jan [cited 2024 Jul 30];72(1):135–6. https://pubmed.ncbi.nlm.nih.gov/19438907/

72.

Zhang T, Ma Q, Shen Q, Jiang C, Zou F, Shen Y et al. Identification of novel biallelic variants in BMP15 in two siblings with premature ovarian insufficiency. J Assist Reprod Genet [Internet]. 2022 Sep 1 [cited 2024 Aug 5];39(9):2125–34. https://pubmed.ncbi.nlm.nih.gov/35861920/

73.

Persani L, Rossetti R, Di pasquale E, Cacciatore C, Fabre S. The fundamental role of bone morphogenetic protein 15 in ovarian function and its involvement in female fertility disorders. Hum Reprod Update [Internet]. 2014 Nov 1 [cited 2024 Jul 28];20(6):869–83. https://pubmed.ncbi.nlm.nih.gov/24980253/

74.

Mehdizadeh A, Soleimani M, Amjadi F, Sene AA, Sheikhha MH, Dehghani A et al. Implication of novel BMP15 and GDF9 variants in unexpected poor ovarian response. Reprod Sci [Internet]. 2024 Mar 1 [cited 2024 Jul 28];31(3):840–50. https://pubmed.ncbi.nlm.nih.gov/37848645/

75.

Afkhami F, Shahbazi S, Farzadi L, Danaei S. Novel bone morphogenetic protein 15 (BMP15) gene variants implicated in premature ovarian insufficiency. Reproductive Biology Endocrinol. 2022;20(1):42.CrossRef

76.

Bione S, Rizzolio F, Sala C, Ricotti R, Goegan M, Manzini MC et al. Mutation analysis of two candidate genes for premature ovarian failure, DACH2 and POF1B. Hum Reprod [Internet]. 2004 [cited 2024 Jul 28];19(12):2759–66. https://pubmed.ncbi.nlm.nih.gov/15459172/

77.

Padovano V, Lucibello I, Alari V, Mina P, Della, Crespi A, Ferrari I et al. The POF1B candidate gene for premature ovarian failure regulates epithelial polarity. J Cell Sci [Internet]. 2011 Oct 1 [cited 2024 Jul 28];124(19):3356–68. https://doi.org/10.1242/jcs.088237

78.

Riva P, Magnani I, Fuhrmann Conti AM, Gelli D, Sala C, Toniolo D et al. FISH characterization of the Xq21 breakpoint in a translocation carrier with premature ovarian failure. Clin Genet [Internet]. 1996 [cited 2024 Jul 29];50(4):267–9. https://pubmed.ncbi.nlm.nih.gov/9001815/

79.

Lacombe A, Lee H, Zahed L, Choucair M, Muller JM, Nelson SF et al. Disruption of POF1B binding to nonmuscle actin filaments is associated with premature ovarian failure. Am J Hum Genet [Internet]. 2006 [cited 2024 Jul 28];79(1):113–9. https://pubmed.ncbi.nlm.nih.gov/16773570/

80.

Cheng L, Zhang J, Ahmad S, Rozier L, Yu H, Deng H et al. Aurora B regulates formin mDia3 in achieving metaphase chromosome alignment. Dev Cell [Internet]. 2011 Mar 3 [cited 2024 Jul 28];20(3):342. /pmc/articles/PMC4581877/

81.

Yasuda S, Oceguera-Yanez F, Kato T, Okamoto M, Yonemura S, Terada Y et al. Cdc42 and mDia3 regulate microtubule attachment to kinetochores. Nature [Internet]. 2004 Apr 15 [cited 2024 Jul 29];428(6984):767–71. https://pubmed.ncbi.nlm.nih.gov/15085137/

82.

Kostrzewska-Poczekaj M, Byzia E, Soloch N, Jarmuz-Szymczak M, Janiszewska J, Kowal E et al. DIAPH2 alterations increase cellular motility and may contribute to the metastatic potential of laryngeal squamous cell carcinoma. Carcinogenesis [Internet]. 2019 Oct 16 [cited 2024 Jul 28];40(10):1251–9. https://pubmed.ncbi.nlm.nih.gov/30793164/

83.

Bione S, Sala C, Manzini C, Arrigo G, Zuffardi O, Banfi S et al. A human homologue of the Drosophila melanogaster diaphanous gene is disrupted in a patient with premature ovarian failure: evidence for conserved function in oogenesis and implications for human sterility. Am J Hum Genet. 1998;62(3).

84.

Mandon-Pépin B, Oustry-Vaiman A, Vigier B, Piumi F, Cribiu E, Cotinot C. Expression profiles and chromosomal localization of genes controlling meiosis and follicular development in the sheep ovary. Biol Reprod [Internet]. 2003 Mar 1 [cited 2024 Jul 29];68(3):985–95. https://doi.org/10.1095/biolreprod.102.008557

85.

86.

Genesio R, Mormile A, Licenziati MR, De Brasi D, Leone G, Balzano S et al. Short stature and primary ovarian insufficiency possibly due to chromosomal position effect in a balanced X;1 translocation. Mol Cytogenet [Internet]. 2015 Jul 15 [cited 2024 Jul 28];8(1). /pmc/articles/PMC4501070/

87.

Bestetti I, Castronovo C, Sironi A, Caslini C, Sala C, Rossetti R et al. High-resolution array-CGH analysis on 46,XX patients affected by early onset primary ovarian insufficiency discloses new genes involved in ovarian function. Hum Reprod [Internet]. 2019 Mar 1 [cited 2024 Jul 28];34(3):574. /pmc/articles/PMC6389867/

88.

Rouen A, Rogers E, Kerlan V, Delemer B, Catteau-Jonard S, Reznik Y et al. Whole exome sequencing in a cohort of familial premature ovarian insufficiency cases reveals a broad array of pathogenic or likely pathogenic variants in 50% of families. Fertil Steril [Internet]. 2022 Apr 1 [cited 2024 Jul 29];117(4):843–53. https://pubmed.ncbi.nlm.nih.gov/35115167/

89.

D G, M W, B L, E F. Cloning and tissue expression of two putative steroid membrane receptors. Biol Chem [Internet]. 1998 [cited 2024 Jul 28];379(7):907–30. https://pubmed.ncbi.nlm.nih.gov/9705155/

90.

Guo M, Zhang C, Wang Y, Feng L, Wang Z, Niu W, et al. Progesterone receptor membrane component 1 mediates progesterone-induced suppression of oocyte meiotic prophase I and primordial folliculogenesis. Sci Rep. 2016;6(1):36869.CrossRefPubMedPubMedCentral

91.

Peluso JJ, Liu X, Gawkowska A, Johnston-MacAnanny E. Progesterone activates a progesterone receptor membrane component 1-dependent mechanism that promotes human granulosa/luteal cell survival but not progesterone secretion. J Clin Endocrinol Metab [Internet]. 2009 [cited 2024 Jul 28];94(7):2644–9. https://pubmed.ncbi.nlm.nih.gov/19417032/

92.

Lodde V, Peluso JJ. A novel role for progesterone and progesterone receptor membrane component 1 in regulating spindle microtubule stability during rat and human ovarian cell mitosis. Biol Reprod [Internet]. 2011 Apr 1 [cited 2024 Jul 28];84(4):715. /pmc/articles/PMC3062038/

93.

Terzaghi L, Tessaro I, Raucci F, Merico V, Mazzini G, Garagna S et al. PGRMC1 participates in late events of bovine granulosa cells mitosis and oocyte meiosis. Cell Cycle [Internet]. 2016 Aug 2 [cited 2024 Jul 29];15(15):2019–32. https://pubmed.ncbi.nlm.nih.gov/27260975/

94.

Mansouri MR, Schuster J, Badhai J, Stattin EL, Lösel R, Wehling M et al. Alterations in the expression, structure and function of progesterone receptor membrane component-1 (PGRMC1) in premature ovarian failure. Hum Mol Genet [Internet]. 2008 [cited 2024 Jul 28];17(23):3776–83. https://pubmed.ncbi.nlm.nih.gov/18782852/

95.

Chen CP, Su YN, Lin HH, Chern SR, Tsai FJ, Wu PC et al. De novo duplication of Xq22.1→q24 with a disruption of the NXF gene cluster in a mentally retarded woman with short stature and premature ovarian failure. Taiwan J Obstet Gynecol [Internet]. 2011 Sep [cited 2024 Jul 28];50(3):339–44. https://pubmed.ncbi.nlm.nih.gov/22030050/

96.

Peluso JJ, Liu X, Uliasz T, Pru CA, Kelp NC, Pru JK. PGRMC1/2 promotes luteal vascularization and maintains the primordial follicles of mice. Reproduction [Internet]. 2018 Oct 1 [cited 2024 Jul 28];156(4):365–73. https://rep.bioscientifica.com/view/journals/rep/156/4/REP-18-0155.xml

97.

Cahill MA, Jazayeri JA, Catalano SM, Toyokuni S, Kovacevic Z, Richardson DR. The emerging role of progesterone receptor membrane component 1 (PGRMC1) in cancer biology. Biochim Biophys Acta [Internet]. 2016 Dec 1 [cited 2024 Jul 28];1866(2):339–49. https://pubmed.ncbi.nlm.nih.gov/27452206/

98.

Banu SK, Stanley JA, Sivakumar KK, Arosh JA, Barhoumi R, Burghardt RC. Identifying a novel role for X-prolyl aminopeptidase (Xpnpep) 2 in CrVI-induced adverse effects on germ cell nest breakdown and follicle development in rats. Biol Reprod. 2015;92(3):67.CrossRefPubMedPubMedCentral

99.

Prueitt RL, Ross JL, Zinn AR. Physical mapping of nine Xq translocation breakpoints and identification of XPNPEP2 as a premature ovarian failure candidate gene. Cytogenet Cell Genet [Internet]. 2000 [cited 2024 Jul 28];89(1–2):44–50. https://pubmed.ncbi.nlm.nih.gov/10894934/

100.

França MM, Funari MFA, Lerario AM, Santos MG, Nishi MY, Domenice S et al. Screening of targeted panel genes in Brazilian patients with primary ovarian insufficiency. PLoS One [Internet]. 2020 Oct 1 [cited 2024 Jul 28];15(10). https://pubmed.ncbi.nlm.nih.gov/33095795/

101.

Herold A, Suyama M, Rodrigues JP, Braun IC, Kutay U, Carmo-Fonseca M et al. TAP (NXF1) belongs to a multigene family of putative RNA export factors with a conserved modular architecture. Mol Cell Biol [Internet]. 2000 Dec 1 [cited 2024 Jul 28];20(23):8996–9008. https://pubmed.ncbi.nlm.nih.gov/11073998/

102.

Grillo L, Reitano S, Belfiore G, Spalletta A, Amata S, Bottitta M et al. Familial 1.1 Mb deletion in chromosome Xq22.1 associated with mental retardation and behavioural disorders in female patients. Eur J Med Genet [Internet]. 2010 Mar [cited 2024 Jul 28];53(2):113–6. https://pubmed.ncbi.nlm.nih.gov/20096387/

103.

Vanmarsenille L, Verbeeck J, Belet S, Van de Roebroek AJ, Nevelsteen J et al. Generation and Characterization of an Nxf7 Knockout Mouse to Study NXF5 Deficiency in a Patient with Intellectual Disability. PLoS One [Internet]. 2013 May 13 [cited 2024 Jul 29];8(5):e64144. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0064144

104.

Bertini V, Ghirri P, Bicocchi MP, Simi P, Valetto A. Molecular cytogenetic definition of a translocation t(X;15) associated with premature ovarian failure. Fertil Steril [Internet]. 2010 [cited 2024 Jul 28];94(3):1097.e5-1097.e8https://pubmed.ncbi.nlm.nih.gov/20338563/.

105.

Pan J, Eckardt S, Leu NA, Buffone MG, Zhou J, Gerton GL et al. Inactivation of Nxf2 causes defects in male meiosis and age-dependent depletion of spermatogonia. Dev Biol [Internet]. 2009 Jun 1 [cited 2024 Jul 28];330(1):167–74. https://pubmed.ncbi.nlm.nih.gov/19345203/

106.

Heidet L, Dahan K, Zhou J, Xu Z, Cochat P, Gould JDM et al. Deletions of both alpha 5(IV) and alpha 6(IV) collagen genes in Alport syndrome and in Alport syndrome associated with smooth muscle tumours. Hum Mol Genet [Internet]. 1995 [cited 2024 Jul 28];4(1):99–108. https://pubmed.ncbi.nlm.nih.gov/7711741/

107.

Nishimura-Tadaki A, Wada T, Bano G, Gough K, Warner J, Kosho T, et al. Breakpoint determination of X;autosome balanced translocations in four patients with premature ovarian failure. J Hum Genet. 2011;56(2):155–60.CrossRef

108.

Philippart C, Masciangelo R, Camboni A, Donnez J, Dolmans MM. Basal lamina characterization in frozen-thawed and long-term grafted human prepubertal ovarian tissue. Reprod Biomed Online [Internet]. 2021 May 1 [cited 2024 Jul 28];42(5):859–69. https://pubmed.ncbi.nlm.nih.gov/33832866/

109.

Shuyuan Y, Meimei W, Fenghua L, Huishan Z, Min C, Hongchu B et al. hUMSC transplantation restores follicle development in ovary damaged mice via re-establish extracellular matrix (ECM) components. J Ovarian Res [Internet]. 2023 Dec 1 [cited 2024 Jul 29];16(1):1–12. https://ovarianresearch.biomedcentral.com/articles/https://doi.org/10.1186/s13048-023-01217-y

110.

Davis RJ, Harding M, Moayedi Y, Mardon G. Mouse Dach1 and Dach2 are redundantly required for Müllerian duct development. Genesis [Internet]. 2008 Apr [cited 2024 Jul 28];46(4):205–13. https://pubmed.ncbi.nlm.nih.gov/18395837/

111.

Davis RJ, Pesah YI, Harding M, Paylor R, Mardon G. Mouse Dach2 mutants do not exhibit gross defects in eye development or brain function. genesis [Internet]. 2006 Feb 1 [cited 2024 Jul 28];44(2):84–92. https://doi.org/10.1002/gene.20188

112.

Prueitt RL, Chen H, Barnes RI, Zinn AR. Most X;autosome translocations associated with premature ovarian failure do not interrupt X-linked genes. Cytogenet Genome Res [Internet]. 2002 [cited 2024 Jul 28];97(1–2):32–8. https://pubmed.ncbi.nlm.nih.gov/12438735/

113.

Meetei AR, Sechi S, Wallisch M, Yang D, Young MK, Joenje H et al. A Multiprotein Nuclear Complex Connects Fanconi Anemia and Bloom Syndrome. Mol Cell Biol [Internet]. 2003 May 1 [cited 2024 Jul 28];23(10):3417. /pmc/articles/PMC164758/

114.

Tsui V, Crismani W. The fanconi anemia pathway and fertility. Trends Genet [Internet]. 2019 Mar 1 [cited 2024 Jul 29];35(3):199–214. https://pubmed.ncbi.nlm.nih.gov/30683429/

115.

Cen C, Chen J, Lin L, Chen M, Dong F, Shen Z et al. Fancb deficiency causes premature ovarian insufficiency in mice†. Biol Reprod [Internet]. 2022 Sep 1 [cited 2024 Jul 28];107(3):790–9. https://pubmed.ncbi.nlm.nih.gov/35596251/

116.

Kato Y, Alavattam KG, Sin HS, Meetei AR, Pang Q, Andreassen PR, et al. FANCB is essential in the male germline and regulates H3K9 methylation on the sex chromosomes during meiosis. Hum Mol Genet. 2015;24(18):5234–49.CrossRefPubMedPubMedCentral

117.

Malcher A, Stokowy T, Berman A, Olszewska M, Jedrzejczak P, Sielski D et al. Whole-genome sequencing identifies new candidate genes for nonobstructive azoospermia. Andrology [Internet]. 2022 Nov 1 [cited 2024 Jul 28];10(8):1605–24. https://pubmed.ncbi.nlm.nih.gov/36017582/

118.

Moalem S, Babul-Hirji R, Stavropolous DJ, Wherrett D, Bägli DJ, Thomas P et al. XX male sex reversal with genital abnormalities associated with a de novo SOX3 gene duplication. Am J Med Genet A [Internet]. 2012 Jul 1 [cited 2024 Jul 28];158A(7):1759–64. https://onlinelibrary.wiley.com/doi/full/https://doi.org/10.1002/ajmg.a.35390

119.

Sutton E, Hughes J, White S, Sekido R, Tan J, Arboleda V et al. Identification of SOX3 as an XX male sex reversal gene in mice and humans. J Clin Invest [Internet]. 2011 Jan 4 [cited 2024 Jul 29];121(1):328–41. https://pubmed.ncbi.nlm.nih.gov/21183788/

120.

Arya VB, Chawla G, Nambisan AKR, Muhi-Iddin N, Vamvakiti E, Ajzensztejn M, et al. Xq27.1 duplication encompassing SOX3: variable phenotype and smallest duplication associated with hypopituitarism to date - a large case series of unrelated patients and a literature review. Horm Res Paediatr. 2019;92(6):382–9.CrossRefPubMed

121.

McAninch D, Mäkelä JA, La HM, Hughes JN, Lovell-Badge R, Hobbs RM et al. SOX3 promotes generation of committed spermatogonia in postnatal mouse testes. Sci Rep [Internet]. 2020 Dec 1 [cited 2024 Jul 28];10(1). /pmc/articles/PMC7174399/

122.

Bian X, Xie Q, Zhou Y, Wu H, Cui J, Jia L et al. Transcriptional changes of mouse ovary during follicle initial or cyclic recruitment mediated by extra hormone treatment. Life Sci [Internet]. 2021 Jan 1 [cited 2024 Jul 28];264. https://pubmed.ncbi.nlm.nih.gov/33141043/

123.

Weiss J, Meeks JJ, Hurley L, Raverot G, Frassetto A, Jameson JL. Sox3 is required for gonadal function, but not sex determination, in males and females. Mol Cell Biol [Internet]. 2003 Nov 1 [cited 2024 Jul 29];23(22):8084. /pmc/articles/PMC262333/

124.

Davey RA, Grossmann M. Androgen receptor structure, function and biology: from bench to bedside. Clin Biochem Rev [Internet]. 2016 Feb [cited 2024 Jul 28];37(1):3. /pmc/articles/PMC4810760/

125.

Spada ARL, Wilson EM, Lubahn DB, Harding AE, Fischbeck KH. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature. 1991;352:6330 [Internet]. 1991 [cited 2024 Jul 29];352(6330):77–9. https://www.nature.com/articles/352077a0

126.

Gottlieb B, Beitel LK, Nadarajah A, Paliouras M, Trifiro M. The androgen receptor gene mutations database: 2012 update. Hum Mutat [Internet]. 2012 May [cited 2024 Jul 28];33(5):887–94. https://pubmed.ncbi.nlm.nih.gov/22334387/

127.

Hickey TE, Marrocco DL, Amato F, Ritter LJ, Norman RJ, Gilchrist RB et al. Androgens augment the mitogenic effects of oocyte-secreted factors and growth differentiation factor 9 on porcine granulosa cells. Biol Reprod [Internet]. 2005 Oct [cited 2024 Jul 28];73(4):825–32. https://pubmed.ncbi.nlm.nih.gov/15972887/

128.

Vendola KA, Zhou J, Adesanya OO, Weil SJ, Bondy CA. Androgens stimulate early stages of follicular growth in the primate ovary. J Clin Invest [Internet]. 1998 Jun 6 [cited 2024 Jul 29];101(12):2622. /pmc/articles/PMC508852/?report=abstract

129.

Liao B, Qi X, Yun C, Qiao J, Pang Y. Effects of androgen excess-related metabolic disturbances on granulosa cell function and follicular development. Front Endocrinol (Lausanne) [Internet]. 2022 Feb 14 [cited 2024 Jul 28];13:1. /pmc/articles/PMC8883052/

130.

Hu YC, Wang PH, Yeh S, Wang RS, Xie C, Xu Q, S A [Internet]. Subfertility and defective folliculogenesis in female mice lacking androgen receptor. Proc Natl Acad Sci USA. 2004 Aug 3 [cited 2024 Jul 28];101(31):11209–14. https://pubmed.ncbi.nlm.nih.gov/15277682/

131.

Shiina H, Matsumoto T, Sato T, Igarashi K, Miyamoto J, Takemasa S, S A [Internet]. Premature ovarian failure in androgen receptor-deficient mice. Proc Natl Acad Sci USA. 2006 Jan 3 [cited 2024 Jul 29];103(1):224–9. https://pubmed.ncbi.nlm.nih.gov/16373508/

132.

Walters KA, Allan CM, Jimenez M, Lim PR, Davey RA, Zajac JD et al. Female mice haploinsufficient for an inactivated androgen receptor (AR) exhibit age-dependent defects that resemble the AR null phenotype of dysfunctional late follicle development, ovulation, and fertility. Endocrinology [Internet]. 2007 Aug [cited 2024 Jul 29];148(8):3674–84. https://pubmed.ncbi.nlm.nih.gov/17463055/

133.

Koch AJ, Holaska JM. Emerin in health and disease. Semin Cell Dev Biol [Internet]. 2014 [cited 2024 Jul 28];29:95–106. https://pubmed.ncbi.nlm.nih.gov/24365856/

134.

Nastały P, Purushothaman D, Marchesi S, Poli A, Lendenmann T, Kidiyoor GR et al. Role of the nuclear membrane protein Emerin in front-rear polarity of the nucleus. Nat Commun [Internet]. 2020 Dec 1 [cited 2024 Jul 28];11(1). https://pubmed.ncbi.nlm.nih.gov/32358486/

135.

Tsatskis Y, Rosenfeld R, Pearson JD, Boswell C, Qu Y, Kim K et al. The NEMP family supports metazoan fertility and nuclear envelope stiffness. Sci Adv [Internet]. 2020 Aug 1 [cited 2024 Jul 29];6(35). /pmc/articles/PMC7455189/

136.

Nagasaki K, Manabe T, Hanzawa H, Maass N, Tsukada T, Yamaguchi K. Identification of a novel gene, LDOC1, down-regulated in cancer cell lines. Cancer Lett [Internet]. 1999 Jun 1 [cited 2024 Jul 28];140(1–2):227–34. https://pubmed.ncbi.nlm.nih.gov/10403563/

137.

Nagasaki K, Schem C, Von Kaisenberg C, Biallek M, Rösel F, Jonat W et al. Leucine-zipper protein, LDOC1, inhibits NF-kappaB activation and sensitizes pancreatic cancer cells to apoptosis. Int J Cancer [Internet]. 2003 Jul 1 [cited 2024 Jul 28];105(4):454–8. https://pubmed.ncbi.nlm.nih.gov/12712434/

138.

Chen H, Chen S, Chen C, Li A, Wei Z. Leucine zipper downregulated in cancer 1 may serve as a favorable prognostic biomarker by influencing proliferation, colony formation, cell cycle, apoptosis, and migration ability in hepatocellular carcinoma. Front Genet [Internet]. 2022 Jul 25 [cited 2024 Jul 28];13. Available from: /pmc/articles/PMC9358146/.

139.

Inoue M, Takahashi K, Niide O, Shibata M, Fukuzawa M, Ra C. LDOC1, a novel MZF-1-interacting protein, induces apoptosis. FEBS Lett [Internet]. 2005 Jan 31 [cited 2024 Jul 28];579(3):604–8. https://onlinelibrary.wiley.com/doi/full/https://doi.org/10.1016/j.febslet.2004.12.030

140.

Thoompumkal IJ, Rehna K, Anbarasu K, Mahalingam S. Leucine Zipper Down-regulated in Cancer-1 (LDOC1) interacts with Guanine nucleotide binding protein-like 3-like (GNL3L) to modulate Nuclear Factor-kappa B (NF-κB) signaling during cell proliferation. Cell Cycle [Internet]. 2016 Dec 1 [cited 2024 Jul 29];15(23):3251–67. https://pubmed.ncbi.nlm.nih.gov/27764577/

141.

Vitek WS, Pagidas K, Gu G, Pepperell JR, Simpson JL, Tantravahi U et al. Xq;autosome translocation in POF: Xq27.2 deletion resulting in haploinsufficiency for SPANX. J Assist Reprod Genet [Internet]. 2012 Jan [cited 2024 Jul 29];29(1):63–6. https://pubmed.ncbi.nlm.nih.gov/22071885/

142.

Okten G, Gunes S, Onat OE, Tukun A, Ozcelik T, Kocak I. Disruption of HDX gene in premature ovarian failure. Syst Biol Reprod Med [Internet]. 2013 Aug [cited 2024 Jul 28];59(4):218–22. https://pubmed.ncbi.nlm.nih.gov/23441923/

143.

Kwon HJ, Park JE, Song H, Jang CY. DDA3 and Mdp3 modulate Kif2a recruitment onto the mitotic spindle to control minus-end spindle dynamics. J Cell Sci [Internet]. 2016 Jul 15 [cited 2024 Jul 28];129(14):2719–25. https://pubmed.ncbi.nlm.nih.gov/27284004/

144.

Sun X, Shi X, Liu M, Li D, Zhang L, Liu X et al. Mdp3 is a novel microtubule-binding protein that regulates microtubule assembly and stability. Cell Cycle [Internet]. 2011 Nov 15 [cited 2024 Jul 29];10(22):3929–37. https://www.tandfonline.com/doi/abs/https://doi.org/10.4161/cc.10.22.18106

145.

Lu C, Zhang Y, Qin Y, Xu Q, Zhou R, Cui Y et al. Human X chromosome exome sequencing identifies BCORL1 as contributor to spermatogenesis. J Med Genet [Internet]. 2021 Jan 1 [cited 2024 Jul 28];58(1):56–65. https://pubmed.ncbi.nlm.nih.gov/32376790/

146.

Chawan V, Yevate S, Gajbhiye R, Kulkarni V, Parte P. Acetylation/deacetylation and microtubule associated proteins influence flagellar axonemal stability and sperm motility. Biosci Rep [Internet]. 2020 Dec 12 [cited 2024 Jul 28];40(12):20202442. /pmc/articles/PMC7711059/

147.

Khoury E, Yazbek JC, Zarzour M, Chamoun Y, Choueiry E, Bou Khalil R et al. Microduplication on the microtubule-associated protein 7 domain-containing 3 (MAP7D3) gene in a female patient with borderline personality disorder, major depression and a history of oppositional defiant disorder. Encephale [Internet]. 2019 Apr 1 [cited 2024 Jul 28];45(2):188–9. https://pubmed.ncbi.nlm.nih.gov/29415802/

148.

Clemens JW, Kabler HL, Sarap JL, Beyer AR, Li PK, Selcer KW. Steroid sulfatase activity in the rat ovary, cultured granulosa cells, and a granulosa cell line. J Steroid Biochem Mol Biol [Internet]. 2000 Dec 31 [cited 2024 Jul 28];75(4–5):245–52. https://pubmed.ncbi.nlm.nih.gov/11282278/

149.

Tšuiko O, Nõukas M, Zilina O, Hensen K, Tapanainen JS, Mägi R et al. Copy number variation analysis detects novel candidate genes involved in follicular growth and oocyte maturation in a cohort of premature ovarian failure cases. Hum Reprod [Internet]. 2016 Aug 1 [cited 2024 Jul 29];31(8):1913–25. https://pubmed.ncbi.nlm.nih.gov/27301361/

150.

Palmer MS, Berta P, Sinclair AH, Pym B, Goodfellow PN. Comparison of human ZFY and ZFX transcripts. Proc Natl Acad Sci U S A [Internet]. 1990 [cited 2024 Jul 28];87(5):1681. /pmc/articles/PMC53546/?report=abstract

151.

Luoh SW, Bain PA, Polakiewicz RD, Goodheart ML, Gardner H, Jaenisch R et al. Zfx mutation results in small animal size and reduced germ cell number in male and female mice. Development [Internet]. 1997 Jun [cited 2024 Jul 28];124(11):2275–84. https://pubmed.ncbi.nlm.nih.gov/9187153/

152.

Ford EA, Frost ER, Beckett EL, Roman SD, McLaughlin EA, Sutherland JM. Transcriptomic profiling of neonatal mouse granulosa cells reveals new insights into primordial follicle activation. Biol Reprod [Internet]. 2022 Mar 1 [cited 2024 Jul 28];106(3):503. /pmc/articles/PMC8934697/

153.

Chen S, Wang G, Zheng X, Ge S, Dai Y, Ping P, et al. Whole-exome sequencing of a large Chinese azoospermia and severe oligospermia cohort identifies novel infertility causative variants and genes. Hum Mol Genet. 2020;29(14):2451–9.CrossRefPubMed

154.

Moortgat S, Berland S, Aukrust I, Maystadt I, Baker L, Benoit V et al. HUWE1 variants cause dominant X-linked intellectual disability: a clinical study of 21 patients. Eur J Hum Genet [Internet]. 2018 Jan 1 [cited 2024 Jul 28];26(1):64–74. https://pubmed.ncbi.nlm.nih.gov/29180823/

155.

Eisa AA, Bang S, Crawford KJ, Murphy EM, Feng WW, Dey S et al. X-Linked Huwe1 is essential for oocyte maturation and preimplantation embryo development. iScience [Internet]. 2020 Sep 25 [cited 2024 Jul 28];23(9). https://pubmed.ncbi.nlm.nih.gov/32927266/

156.

Murtaza M, Jolly LA, Gecz J, Wood SA, La FAM. fatale: USP9X in development and disease. Cell Mol Life Sci [Internet]. 2015 Jun 1 [cited 2024 Jul 28];72(11):2075. /pmc/articles/PMC4427618/

157.

Noma T, Kanai Y, Kanai-Azuma M, Ishii M, Fujisawa M, Kurohmaru M et al. Stage- and sex-dependent expressions of Usp9x, an X-linked mouse ortholog of Drosophila Fat facets, during gonadal development and oogenesis in mice. Gene Expression Patterns [Internet]. 2002 Nov [cited 2024 Jul 28];2(1–2):87–91. https://pubmed.ncbi.nlm.nih.gov/12617843/

158.

Quilter CR, Karcanias AC, Bagga MR, Duncan S, Murray A, Conway GS et al. Analysis of X chromosome genomic DNA sequence copy number variation associated with premature ovarian failure (POF). Hum Reprod [Internet]. 2010 [cited 2024 Jul 28];25(8):2139–50. https://pubmed.ncbi.nlm.nih.gov/20570974/

159.

Furtado CLM, Soares MR, Verruma CG, de Oliveira Gennaro FG, da Silva LECM, Ferriani RA et al. BCORL1, POF1B, and USP9X copy number variation in women with idiopathic diminished ovarian reserve. J Assist Reprod Genet [Internet]. 2024 Jul 12 [cited 2024 Jul 28];1–10. https://link.springer.com/article/https://doi.org/10.1007/s10815-024-03185-8

160.

Wang X, Lu G, Li L, Yi J, Yan K, Wang Y et al. HUWE1 interacts with BRCA1 and promotes its degradation in the ubiquitin-proteasome pathway. Biochem Biophys Res Commun [Internet]. 2014 Feb 14 [cited 2024 Jul 29];444(3):290–5. https://pubmed.ncbi.nlm.nih.gov/24342616/

161.

Lu Q, Zhang FL, Lu DY, Shao ZM, Li DQ. USP9X stabilizes BRCA1 and confers resistance to DNA-damaging agents in human cancer cells. Cancer Med [Internet]. 2019 Nov 1 [cited 2024 Jul 28];8(15):6730. /pmc/articles/PMC6825982/

162.

Gomez-Bougie P, Ménoret E, Juin P, Dousset C, Pellat-Deceunynck C, Amiot M. Noxa controls Mule-dependent Mcl-1 ubiquitination through the regulation of the Mcl-1/USP9X interaction. Biochem Biophys Res Commun [Internet]. 2011 Sep 30 [cited 2024 Jul 28];413(3):460–4. https://pubmed.ncbi.nlm.nih.gov/21907705/

163.

Ruth KS, Day FR, Hussain J, Martínez-Marchal A, Aiken CE, Azad A et al. Genetic insights into biological mechanisms governing human ovarian ageing. Nature [Internet]. 2021 Aug 19 [cited 2024 Jul 29];596(7872):393–7. https://pubmed.ncbi.nlm.nih.gov/34349265/

164.

Omari S, Waters M, Naranian T, Kim K, Perumalsamy AL, Chi M et al. Mcl-1 is a key regulator of the ovarian reserve. Cell Death Dis [Internet]. 2015 May 1 [cited 2024 Jul 28];6(5):e1755. /pmc/articles/PMC4669721/

165.

Oral E, Toksoy G, Sofiyeva N, Celik HG, Karaman B, Basaran S et al. Clinical and genetic investigation of premature ovarian insufficiency cases from Turkey. J Gynecol Obstet Hum Reprod [Internet]. 2019 Dec 1 [cited 2024 Jul 30];48(10):817–23. https://pubmed.ncbi.nlm.nih.gov/31026518/

166.

Yuan ZZ, Wang CY, Jin JY, Sheng Y, Zhao MF, Fan LL et al. A novel POF1B variant in a Chinese patient is associated with premature ovarian failure. Clin Genet [Internet]. 2021 Dec 1 [cited 2024 Jul 30];100(6):773–4. https://pubmed.ncbi.nlm.nih.gov/34423420/

167.

Tucker EJ, Bell KM, van den Robevska G, Ayers KL, Listyasari N et al. Meiotic genes in premature ovarian insufficiency: variants in HROB and REC8 as likely genetic causes. European Journal of Human Genetics [Internet]. 2022 Feb 1 [cited 2024 Jul 30];30(2):219. /pmc/articles/PMC8821714/

168.

Tang R, Yu Q. Novel variants in women with premature ovarian function decline identified via whole-exome sequencing. J Assist Reprod Genet [Internet]. 2020 Oct 1 [cited 2024 Jul 30];37(10):2487–502. https://pubmed.ncbi.nlm.nih.gov/32789750/

169.

Dioguardi CC, Uslu B, Haynes M, Kurus M, Gul M, Miao DQ et al. Granulosa cell and oocyte mitochondrial abnormalities in a mouse model of fragile X primary ovarian insufficiency. Mol Hum Reprod [Internet]. 2016 Jun 16 [cited 2024 Jul 30];22(6):384–96. https://pubmed.ncbi.nlm.nih.gov/26965313/

170.

Mok-Lin E, Ascano M, Serganov A, Rosenwaks Z, Tuschl T, Williams Z. Premature recruitment of oocyte pool and increased mTOR activity in Fmr1 knockout mice and reversal of phenotype with rapamycin. Scientific Rep. 2018;8:1 [Internet]. 2018 Jan 12 [cited 2024 Jul 30];8(1):1–6. https://www.nature.com/articles/s41598-017-18598-y

171.

Forss-Petter S, Werner H, Berger J, Lassmann H, Molzer B, Schwab MH, et al. Targeted inactivation of the X-linked adrenoleukodystrophy gene in mice. J Neurosci Res. 1997;50(5):829–43.CrossRefPubMed

Title: Searching for the ‘X’ factor: investigating the genetics of primary ovarian insufficiency
Authors: Anya Knight
Sara Sugin
Andrea Jurisicova
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Primary Ovarian Insufficiency
Turner's Syndrome
Published in: Journal of Ovarian Research / Issue 1/2024
Electronic ISSN: 1757-2215
DOI: https://doi.org/10.1186/s13048-024-01555-5

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Searching for the ‘X’ factor: investigating the genetics of primary ovarian insufficiency

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