Development of functional spermatozoa in mammalian spermiogenesis

Development, Год журнала: 2024, Номер 151(14)

Опубликована: Июль 15, 2024

ABSTRACT Infertility is a global health problem affecting one in six couples, with 50% of cases attributed to male infertility. Spermatozoa are gametes, specialized cells that can be divided into two parts: the head and flagellum. The contains vesicle called acrosome undergoes exocytosis flagellum motility apparatus propels spermatozoa forward components, axonemes accessory structures. For fertilize oocytes, must formed correctly. In this Review, we describe comprehensively how functional develop mammals during spermiogenesis, including formation acrosomes, structures by focusing on analyses mouse models.

Язык: Английский

---

Deficiency in DNAH12 causes male infertility by impairing DNAH1 and DNALI1 recruitment in humans and mice

Опубликована: Фев. 13, 2025

Asthenoteratozoospermia, a prevalent cause of male infertility, lacks well-defined etiology. DNAH12 is special dynein featured by the absence microtubule-binding domain, however, its functions in spermatogenesis remain largely unknown. Through comprehensive genetic analyses involving whole-exome sequencing and subsequent Sanger on infertile patients fertile controls from six distinct families, we unveiled biallelic mutations that co-segregate recessively with infertility studied families. Transmission electron microscopy (TEM) revealed pronounced axonemal abnormalities, including inner arms (IDAs) impairment central pair (CP) loss sperm flagella patients. Mouse models ( Dnah12 −/− mut/mut ) were generated recapitulated reproductive defects Noteworthy, deficiency did not show effects cilium organization function. Mechanistically, was confirmed to interact two other IDA components DNALI1 DNAH1, while disruption leads failed recruitment DNAH1 IDAs compromised development. Furthermore, also interacts radial spoke head proteins RSPH1, RSPH9, DNAJB13 regulate CP stability. Moreover, mice could be overcome intracytoplasmic injection (ICSI) treatment. Collectively, plays crucial role proper axoneme flagella, but cilia, recruiting both humans mice. These findings expand our comprehension component assembly cilia provide valuable marker for counseling diagnosis asthenoteratozoospermia clinical practice.

Язык: Английский

---

Novel bi-allelic variants in DNAH10 lead to multiple morphological abnormalities of sperm flagella and male infertility

Asian Journal of Andrology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Abstract Multiple morphological abnormalities of sperm flagella (MMAF) is a severe form asthenoteratozoospermia, characterized by and reduced motility sperm, causing male infertility. Although approximately 60% MMAF cases can be explained genetically, the etiology remaining unclear. Here, we identified two novel compound heterozygous variants in gene, dynein axonemal heavy chain 10 ( DNAH10 ), three patients from unrelated Pakistani families using whole-exome sequencing (WES), including one mutation : c.9409C>A [p.P3137T]; c.12946G>C [p.D4316H]) family 1 another c.8849G>A [p.G2950D]; c.11509C>T [p.R3687W]) 2. All are absent or rare public genome databases predicted to have deleterious effects according multiple bioinformatic tools. Sanger revealed that these follow an autosomal recessive mode inheritance. Hematoxylin eosin (H&E) staining MMAF, head abnormalities, patients. In addition, immunofluorescence loss protein signals along flagella. These findings broaden spectrum expand understanding genetic basis infertility associated with phenotype.

Язык: Английский

---

Deficiency in DNAH12 causes male infertility by impairing DNAH1 and DNALI1 recruitment in humans and mice

eLife, Год журнала: 2025, Номер 13

Опубликована: Март 27, 2025

Asthenoteratozoospermia, a prevalent cause of male infertility, lacks well-defined etiology. DNAH12 is special dynein featured by the absence microtubule-binding domain, however, its functions in spermatogenesis remain largely unknown. Through comprehensive genetic analyses involving whole-exome sequencing and subsequent Sanger on infertile patients fertile controls from six distinct families, we unveiled biallelic mutations that co-segregate recessively with infertility studied families. Transmission electron microscopy (TEM) revealed pronounced axonemal abnormalities, including inner arms (IDAs) impairment central pair (CP) loss sperm flagella patients. Mouse models ( Dnah12 -/- mut/mut ) were generated recapitulated reproductive defects Noteworthy, deficiency did not show effects cilium organization function. Mechanistically, was confirmed to interact two other IDA components DNALI1 DNAH1, while disruption leads failed recruitment DNAH1 IDAs compromised development. Furthermore, also interacts radial spoke head proteins RSPH1, RSPH9, DNAJB13 regulate CP stability. Moreover, mice could be overcome intracytoplasmic injection (ICSI) treatment. Collectively, plays crucial role proper axoneme flagella, but cilia, recruiting both humans mice. These findings expand our comprehension component assembly cilia provide valuable marker for counseling diagnosis asthenoteratozoospermia clinical practice.

Язык: Английский

---

The Role of Z Chromosome Localization Gene psmd9 in Spermatogenesis of Cynoglossus semilaevis

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6372 - 6372

Опубликована: Июнь 9, 2024

Proteasome 26S Subunit, Non-ATPase 9 (

Язык: Английский

---

Deficiency in a special dynein DNAH12 causes male infertility by impairing DNAH1 and DNALI1 recruitment in humans and mice

Опубликована: Авг. 27, 2024

Asthenoteratozoospermia, a prevalent cause of male infertility, lacks well-defined etiology. DNAH12 is special dynein featured by the absence microtubule-binding domain, however, its functions in spermatogenesis remain largely unknown. Through comprehensive genetic analyses involving whole-exome sequencing and subsequent Sanger on infertile patients fertile controls from six distinct families, we unveiled biallelic mutations that co-segregate recessively with infertility studied families. Transmission electron microscopy (TEM) revealed pronounced axonemal abnormalities, including inner arms (IDAs) impairment central pair (CP) loss sperm flagella patients. Mouse models ( Dnah12 −/− mut/mut ) were generated recapitulated reproductive defects Noteworthy, deficiency did not show effects cilium organization function. Mechanistically, was confirmed to interact two other IDA components DNALI1 DNAH1, while disruption leads failed recruitment DNAH1 IDAs compromised development. Furthermore, also interacts radial spoke head proteins RSPH1, RSPH9, DNAJB13 regulate CP stability. Moreover, mice could be overcome intracytoplasmic injection (ICSI) treatment. Collectively, plays crucial role proper axoneme flagella, but cilia, recruiting both humans mice. These findings expand our comprehension component assembly cilia provide valuable marker for counseling diagnosis asthenoteratozoospermia clinical practice.

Язык: Английский

---

DNAH3 deficiency causes flagellar inner dynein arm loss and male infertility in humans and mice

eLife, Год журнала: 2024, Номер 13

Опубликована: Май 28, 2024

Axonemal protein complexes, including the outer and inner dynein arms (ODA/IDA), are highly ordered structures of sperm flagella that drive motility. Deficiencies in several axonemal proteins have been associated with male infertility, which is characterized by asthenozoospermia or asthenoteratozoospermia. Dynein heavy chain 3 (DNAH3) resides IDA expressed testis. However, relationship between DNAH3 infertility still unclear. Herein, we identified biallelic variants four unrelated Han Chinese infertile men asthenoteratozoospermia through whole-exome sequencing (WES). These contributed to deficient expression patients’ flagella. Importantly, patients represented anomalous flagellar morphology, ultrastructure was severely disrupted. Intriguingly, Dnah3 knockout (KO) mice were also infertile, especially showing severe reduction movement abnormal mitochondrion structure. Mechanically, nonfunctional resulted decreased IDA-associated spermatozoa KO mice, DNAH1, DNAH6, DNALI1, deletion has involved disruption Moreover, could be rescued intracytoplasmic injection (ICSI) treatment. Our findings indicated a novel pathogenic gene for may further contribute diagnosis, genetic counseling, prognosis infertility.

Язык: Английский

---

Novel bi-allelic DNAH3 variants cause oligoasthenoteratozoospermia

Frontiers in Endocrinology, Год журнала: 2024, Номер 15

Опубликована: Окт. 28, 2024

Oligoasthenoteratozoospermia (OAT) is a widespread cause of male infertility. One the usual clinical manifestations OAT multiple morphological abnormalities sperm flagella (MMAF), which are frequently associated with mutations and defects in dynein family. However, relationship between newly identified Dynein Axonemal Heavy Chain 3 (DNAH3) mutation oligonasthenospermia humans has not yet been established.

Язык: Английский

---

DNAH3 deficiency causes flagellar inner dynein arm loss and male infertility in humans and mice

eLife, Год журнала: 2024, Номер 13

Опубликована: Ноя. 6, 2024

Axonemal protein complexes, including the outer and inner dynein arms (ODA/IDA), are highly ordered structures of sperm flagella that drive motility. Deficiencies in several axonemal proteins have been associated with male infertility, which is characterized by asthenozoospermia or asthenoteratozoospermia. Dynein heavy chain 3 (DNAH3) resides IDA expressed testis. However, relationship between DNAH3 infertility still unclear. Herein, we identified biallelic variants four unrelated Han Chinese infertile men asthenoteratozoospermia through whole-exome sequencing (WES). These contributed to deficient expression patients’ flagella. Importantly, patients represented anomalous flagellar morphology, ultrastructure was severely disrupted. Intriguingly, Dnah3 knockout (KO) mice were also infertile, especially showing severe reduction movement abnormal mitochondrion structure. Mechanically, nonfunctional resulted decreased IDA-associated spermatozoa KO mice, DNAH1, DNAH6, DNALI1, deletion has involved disruption Moreover, could be rescued intracytoplasmic injection (ICSI) treatment. Our findings indicated a novel pathogenic gene for may further contribute diagnosis, genetic counseling, prognosis infertility.

Язык: Английский

---

Genetic Polymorphisms in Genes Associated with Mammalian Semen Quality Traits: A Review

Agriculture, Год журнала: 2024, Номер 14(12), С. 2137 - 2137

Опубликована: Ноя. 25, 2024

Semen quality traits, including sperm morphology, shape, count, ejaculate volume, low percentage of motile spermatozoa in semen, and motility, play a crucial role male reproductive efficiency fertilization success. This review article highlighted the impact genetic polymorphisms genes on semen fertility traits mammalians. Single nucleotide (SNPs) these were associated with various abnormalities, such as abnormal flagella reduced impaired DNA integrity, altered antioxidant status, disrupted head–tail junction, spermatogenesis defects, testicular size, range disorders. comprehensive available literature offers significant insights into factors influencing which can contribute to development markers enhancement through assisted selective breeding programs.

Язык: Английский

---