Spermatogenic failure is reflected in a lower or absent production of spermatozoa and is described by routine semen analysis using terms such as azoospermia, oligozoospermia, teratozoospermia or asthenozoospermia. The genetic causes of spermatogenetic failure still remain largely unknown. It has been estimated that more than 2300 genes play a role in spermatogenesis.
Category
Reproductive system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
16 Diseases of the genitourinary system
Diseases of the male genital system
GB04 Male infertility
H01282 Spermatogenic failure
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06530 PI3K signaling
H01282 Spermatogenic failure
Kusz-Zamelczyk K, Sajek M, Spik A, Glazar R, Jedrzejczak P, Latos-Bielenska A, Kotecki M, Pawelczyk L, Jaruzelska J
Title
Mutations of NANOS1, a human homologue of the Drosophila morphogen, are associated with a lack of germ cells in testes or severe oligo-astheno-teratozoospermia.
Amiri-Yekta A, Coutton C, Kherraf ZE, Karaouzene T, Le Tanno P, Sanati MH, Sabbaghian M, Almadani N, Sadighi Gilani MA, Hosseini SH, Bahrami S, Daneshipour A, Bini M, Arnoult C, Colombo R, Gourabi H, Ray PF
Title
Whole-exome sequencing of familial cases of multiple morphological abnormalities of the sperm flagella (MMAF) reveals new DNAH1 mutations.
Dong FN, Amiri-Yekta A, Martinez G, Saut A, Tek J, Stouvenel L, Lores P, Karaouzene T, Thierry-Mieg N, Satre V, Brouillet S, Daneshipour A, Hosseini SH, Bonhivers M, Gourabi H, Dulioust E, Arnoult C, Toure A, Ray PF, Zhao H, Coutton C
Title
Absence of CFAP69 Causes Male Infertility due to Multiple Morphological Abnormalities of the Flagella in Human and Mouse.
Okutman O, Muller J, Baert Y, Serdarogullari M, Gultomruk M, Piton A, Rombaut C, Benkhalifa M, Teletin M, Skory V, Bakircioglu E, Goossens E, Bahceci M, Viville S
Title
Exome sequencing reveals a nonsense mutation in TEX15 causing spermatogenic failure in a Turkish family.
Lores P, Coutton C, El Khouri E, Stouvenel L, Givelet M, Thomas L, Rode B, Schmitt A, Louis B, Sakheli Z, Chaudhry M, Fernandez-Gonzales A, Mitsialis A, Dacheux D, Wolf JP, Papon JF, Gacon G, Escudier E, Arnoult C, Bonhivers M, Savinov SN, Amselem S, Ray PF, Dulioust E, Toure A
Title
Homozygous missense mutation L673P in adenylate kinase 7 (AK7) leads to primary male infertility and multiple morphological anomalies of the flagella but not to primary ciliary dyskinesia.
Kherraf ZE, Amiri-Yekta A, Dacheux D, Karaouzene T, Coutton C, Christou-Kent M, Martinez G, Landrein N, Le Tanno P, Fourati Ben Mustapha S, Halouani L, Marrakchi O, Makni M, Latrous H, Kharouf M, Pernet-Gallay K, Gourabi H, Robinson DR, Crouzy S, Blum M, Thierry-Mieg N, Toure A, Zouari R, Arnoult C, Bonhivers M, Ray PF
Title
A Homozygous Ancestral SVA-Insertion-Mediated Deletion in WDR66 Induces Multiple Morphological Abnormalities of the Sperm Flagellum and Male Infertility.
Martinez G, Kherraf ZE, Zouari R, Fourati Ben Mustapha S, Saut A, Pernet-Gallay K, Bertrand A, Bidart M, Hograindleur JP, Amiri-Yekta A, Kharouf M, Karaouzene T, Thierry-Mieg N, Dacheux-Deschamps D, Satre V, Bonhivers M, Toure A, Arnoult C, Ray PF, Coutton C
Title
Whole-exome sequencing identifies mutations in FSIP2 as a recurrent cause of multiple morphological abnormalities of the sperm flagella.
Shen Y, Zhang F, Li F, Jiang X, Yang Y, Li X, Li W, Wang X, Cheng J, Liu M, Zhang X, Yuan G, Pei X, Cai K, Hu F, Sun J, Yan L, Tang L, Jiang C, Tu W, Xu J, Wu H, Kong W, Li S, Wang K, Sheng K, Zhao X, Yue H, Yang X, Xu W
Title
Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella.
Guran T, Yesil G, Turan S, Atay Z, Bozkurtlar E, Aghayev A, Gul S, Tinay I, Aru B, Arslan S, Koroglu MK, Ercan F, Demirel GY, Eren FS, Karademir B, Bereket A
Title
PPP2R3C gene variants cause syndromic 46,XY gonadal dysgenesis and impaired spermatogenesis in humans.
Liu W, He X, Yang S, Zouari R, Wang J, Wu H, Kherraf ZE, Liu C, Coutton C, Zhao R, Tang D, Tang S, Lv M, Fang Y, Li W, Li H, Zhao J, Wang X, Zhao S, Zhang J, Arnoult C, Jin L, Zhang Z, Ray PF, Cao Y, Zhang F
Title
Bi-allelic Mutations in TTC21A Induce Asthenoteratospermia in Humans and Mice.
Coutton C, Martinez G, Kherraf ZE, Amiri-Yekta A, Boguenet M, Saut A, He X, Zhang F, Cristou-Kent M, Escoffier J, Bidart M, Satre V, Conne B, Fourati Ben Mustapha S, Halouani L, Marrakchi O, Makni M, Latrous H, Kharouf M, Pernet-Gallay K, Bonhivers M, Hennebicq S, Rives N, Dulioust E, Toure A, Gourabi H, Cao Y, Zouari R, Hosseini SH, Nef S, Thierry-Mieg N, Arnoult C, Ray PF
Title
Bi-allelic Mutations in ARMC2 Lead to Severe Astheno-Teratozoospermia Due to Sperm Flagellum Malformations in Humans and Mice.
Beurois J, Martinez G, Cazin C, Kherraf ZE, Amiri-Yekta A, Thierry-Mieg N, Bidart M, Petre G, Satre V, Brouillet S, Toure A, Arnoult C, Ray PF, Coutton C
Title
CFAP70 mutations lead to male infertility due to severe astheno-teratozoospermia. A case report.
Lores P, Dacheux D, Kherraf ZE, Nsota Mbango JF, Coutton C, Stouvenel L, Ialy-Radio C, Amiri-Yekta A, Whitfield M, Schmitt A, Cazin C, Givelet M, Ferreux L, Fourati Ben Mustapha S, Halouani L, Marrakchi O, Daneshipour A, El Khouri E, Do Cruzeiro M, Favier M, Guillonneau F, Chaudhry M, Sakheli Z, Wolf JP, Patrat C, Gacon G, Savinov SN, Hosseini SH, Robinson DR, Zouari R, Ziyyat A, Arnoult C, Dulioust E, Bonhivers M, Ray PF, Toure A
Title
Mutations in TTC29, Encoding an Evolutionarily Conserved Axonemal Protein, Result in Asthenozoospermia and Male Infertility.
Liu C, Lv M, He X, Zhu Y, Amiri-Yekta A, Li W, Wu H, Kherraf ZE, Liu W, Zhang J, Tan Q, Tang S, Zhu YJ, Zhong Y, Li C, Tian S, Zhang Z, Jin L, Ray P, Zhang F, Cao Y
Title
Homozygous mutations in SPEF2 induce multiple morphological abnormalities of the sperm flagella and male infertility.
Liu C, Miyata H, Gao Y, Sha Y, Tang S, Xu Z, Whitfield M, Patrat C, Wu H, Dulioust E, Tian S, Shimada K, Cong J, Noda T, Li H, Morohoshi A, Cazin C, Kherraf ZE, Arnoult C, Jin L, He X, Ray PF, Cao Y, Toure A, Zhang F, Ikawa M
Title
Bi-allelic DNAH8 Variants Lead to Multiple Morphological Abnormalities of the Sperm Flagella and Primary Male Infertility.
Lv M, Liu W, Chi W, Ni X, Wang J, Cheng H, Li WY, Yang S, Wu H, Zhang J, Gao Y, Liu C, Li C, Yang C, Tan Q, Tang D, Zhang J, Song B, Chen YJ, Li Q, Zhong Y, Zhang Z, Saiyin H, Jin L, Xu Y, Zhou P, Wei Z, Zhang C, He X, Zhang F, Cao Y
Title
Homozygous mutations in DZIP1 can induce asthenoteratospermia with severe MMAF.
Wyrwoll MJ, Temel SG, Nagirnaja L, Oud MS, Lopes AM, van der Heijden GW, Heald JS, Rotte N, Wistuba J, Woste M, Ledig S, Krenz H, Smits RM, Carvalho F, Goncalves J, Fietz D, Turkgenc B, Ergoren MC, Cetinkaya M, Basar M, Kahraman S, McEleny K, Xavier MJ, Turner H, Pilatz A, Ropke A, Dugas M, Kliesch S, Neuhaus N, Aston KI, Conrad DF, Veltman JA, Friedrich C, Tuttelmann F
Title
Bi-allelic Mutations in M1AP Are a Frequent Cause of Meiotic Arrest and Severely Impaired Spermatogenesis Leading to Male Infertility.
He X, Liu C, Yang X, Lv M, Ni X, Li Q, Cheng H, Liu W, Tian S, Wu H, Gao Y, Yang C, Tan Q, Cong J, Tang D, Zhang J, Song B, Zhong Y, Li H, Zhi W, Mao X, Fu F, Ge L, Shen Q, Zhang M, Saiyin H, Jin L, Xu Y, Zhou P, Wei Z, Zhang F, Cao Y
Title
Bi-allelic Loss-of-function Variants in CFAP58 Cause Flagellar Axoneme and Mitochondrial Sheath Defects and Asthenoteratozoospermia in Humans and Mice.
Martinez G, Beurois J, Dacheux D, Cazin C, Bidart M, Kherraf ZE, Robinson DR, Satre V, Le Gac G, Ka C, Gourlaouen I, Fichou Y, Petre G, Dulioust E, Zouari R, Thierry-Mieg N, Toure A, Arnoult C, Bonhivers M, Ray P, Coutton C
Title
Biallelic variants in MAATS1 encoding CFAP91, a calmodulin-associated and spoke-associated complex protein, cause severe astheno-teratozoospermia and male infertility.
Fan S, Jiao Y, Khan R, Jiang X, Javed AR, Ali A, Zhang H, Zhou J, Naeem M, Murtaza G, Li Y, Yang G, Zaman Q, Zubair M, Guan H, Zhang X, Ma H, Jiang H, Ali H, Dil S, Shah W, Ahmad N, Zhang Y, Shi Q
Title
Homozygous mutations in C14orf39/SIX6OS1 cause non-obstructive azoospermia and premature ovarian insufficiency in humans.
Tu C, Cong J, Zhang Q, He X, Zheng R, Yang X, Gao Y, Wu H, Lv M, Gu Y, Lu S, Liu C, Tian S, Meng L, Wang W, Tan C, Nie H, Li D, Zhang H, Gong F, Hu L, Lu G, Xu W, Lin G, Zhang F, Cao Y, Tan YQ
Title
Bi-allelic mutations of DNAH10 cause primary male infertility with asthenoteratozoospermia in humans and mice.
Nagirnaja L, Morup N, Nielsen JE, Stakaitis R, Golubickaite I, Oud MS, Winge SB, Carvalho F, Aston KI, Khani F, van der Heijden GW, Marques CJ, Skakkebaek NE, Rajpert-De Meyts E, Schlegel PN, Jorgensen N, Veltman JA, Lopes AM, Conrad DF, Almstrup K
Title
Variant PNLDC1, Defective piRNA Processing, and Azoospermia.
Lores P, Kherraf ZE, Amiri-Yekta A, Whitfield M, Daneshipour A, Stouvenel L, Cazin C, Cavarocchi E, Coutton C, Llabador MA, Arnoult C, Thierry-Mieg N, Ferreux L, Patrat C, Hosseini SH, Mustapha SFB, Zouari R, Dulioust E, Ray PF, Toure A
Title
A missense mutation in IFT74, encoding for an essential component for intraflagellar transport of Tubulin, causes asthenozoospermia and male infertility without clinical signs of Bardet-Biedl syndrome.
Krausz C, Riera-Escamilla A, Moreno-Mendoza D, Holleman K, Cioppi F, Algaba F, Pybus M, Friedrich C, Wyrwoll MJ, Casamonti E, Pietroforte S, Nagirnaja L, Lopes AM, Kliesch S, Pilatz A, Carrell DT, Conrad DF, Ars E, Ruiz-Castane E, Aston KI, Baarends WM, Tuttelmann F
Title
Genetic dissection of spermatogenic arrest through exome analysis: clinical implications for the management of azoospermic men.
Riera-Escamilla A, Enguita-Marruedo A, Moreno-Mendoza D, Chianese C, Sleddens-Linkels E, Contini E, Benelli M, Natali A, Colpi GM, Ruiz-Castane E, Maggi M, Baarends WM, Krausz C
Title
Sequencing of a 'mouse azoospermia' gene panel in azoospermic men: identification of RNF212 and STAG3 mutations as novel genetic causes of meiotic arrest.
Wyrwoll MJ, van Walree ES, Hamer G, Rotte N, Motazacker MM, Meijers-Heijboer H, Alders M, Meissner A, Kaminsky E, Woste M, Krallmann C, Kliesch S, Hunt TJ, Clark AT, Silber S, Stallmeyer B, Friedrich C, van Pelt AMM, Mathijssen IB, Tuttelmann F
Title
Bi-allelic variants in DNA mismatch repair proteins MutS Homolog MSH4 and MSH5 cause infertility in both sexes.
Cong J, Wang X, Amiri-Yekta A, Wang L, Kherraf ZE, Liu C, Cazin C, Tang S, Hosseini SH, Tian S, Daneshipour A, Wang J, Zhou Y, Zeng Y, Yang S, He X, Li J, Cao Y, Jin L, Ray PF, Zhang F
Title
Homozygous mutations in CCDC34 cause male infertility with oligoasthenoteratozoospermia in humans and mice.
Lv M, Liu C, Ma C, Yu H, Shao Z, Gao Y, Liu Y, Wu H, Tang D, Tan Q, Zhang J, Li K, Xu C, Geng H, Zhang J, Li H, Mao X, Ge L, Fu F, Zhong K, Xu Y, Tao F, Zhou P, Wei Z, He X, Zhang F, Cao Y
Title
Homozygous mutation in SLO3 leads to severe asthenoteratozoospermia due to acrosome hypoplasia and mitochondrial sheath malformations.
Liu Y, Li Y, Meng L, Li K, Gao Y, Lv M, Guo R, Xu Y, Zhou P, Wei Z, He X, Cao Y, Wu H, Tan Y, Hua R
Title
Bi-allelic human TEKT3 mutations cause male infertility with oligoasthenoteratozoospermia owing to acrosomal hypoplasia and reduced progressive motility.
Wu H, Liu Y, Li Y, Li K, Xu C, Gao Y, Lv M, Guo R, Xu Y, Zhou P, Wei Z, Hua R, He X, Cao Y
Title
DNALI1 deficiency causes male infertility with severe asthenozoospermia in humans and mice by disrupting the assembly of the flagellar inner dynein arms and fibrous sheath.
Fakhro KA, Elbardisi H, Arafa M, Robay A, Rodriguez-Flores JL, Al-Shakaki A, Syed N, Mezey JG, Abi Khalil C, Malek JA, Al-Ansari A, Al Said S, Crystal RG
Title
Point-of-care whole-exome sequencing of idiopathic male infertility.
Ma A, Zhou J, Ali H, Abbas T, Ali I, Muhammad Z, Dil S, Chen J, Huang X, Ma H, Zhao D, Zhang B, Zhang Y, Shah W, Shah B, Murtaza G, Iqbal F, Khan MA, Khan A, Li Q, Xu B, Wu L, Zhang H, Shi Q
Title
Loss-of-function mutations in CFAP57 cause multiple morphological abnormalities of the flagella in humans and mice.
Yatsenko AN, Georgiadis AP, Ropke A, Berman AJ, Jaffe T, Olszewska M, Westernstroer B, Sanfilippo J, Kurpisz M, Rajkovic A, Yatsenko SA, Kliesch S, Schlatt S, Tuttelmann F
Title
X-linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men.
Liu C, Tu C, Wang L, Wu H, Houston BJ, Mastrorosa FK, Zhang W, Shen Y, Wang J, Tian S, Meng L, Cong J, Yang S, Jiang Y, Tang S, Zeng Y, Lv M, Lin G, Li J, Saiyin H, He X, Jin L, Toure A, Ray PF, Veltman JA, Shi Q, O'Bryan MK, Cao Y, Tan YQ, Zhang F
Title
Deleterious variants in X-linked CFAP47 induce asthenoteratozoospermia and primary male infertility.
Liu C, Si W, Tu C, Tian S, He X, Wang S, Yang X, Yao C, Li C, Kherraf ZE, Ye M, Zhou Z, Ma Y, Gao Y, Li Y, Liu Q, Tang S, Wang J, Saiyin H, Zhao L, Yang L, Meng L, Chen B, Tang D, Zhou Y, Wu H, Lv M, Tan C, Lin G, Kong Q, Shi H, Su Z, Li Z, Yao YG, Jin L, Zheng P, Ray PF, Tan YQ, Cao Y, Zhang F
Title
Deficiency of primate-specific SSX1 induced asthenoteratozoospermia in infertile men and cynomolgus monkey and tree shrew models.
