Genetic Underpinnings of Oligoasthenoteratozoospermia

Clinical Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

ABSTRACT Oligoasthenoteratozoospermia (OAT) is a frequent but severe type of male infertility. As one the most multifaceted infertility resulting from sperm problems, its genetic etiology remains unknown in cases. In this review, we systematically sort out latest literature on clinical reports and animal models leading to OAT, summarise expression profiles causative genes for highlight important role protein transport system during spermiogenesis, spermatid cell‐specific genes, Golgi acrosome‐related manchette‐related HTCA‐related axoneme‐related OAT development. These would be instrumental etiological screening, counseling, pre‐implantation testing patients with OAT.

Language: Английский

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Loss of Cep135 causes oligoasthenoteratozoospermia and male infertility in mice

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: March 17, 2025

Centrosomal proteins (Cep), as crucial scaffolding molecules, play a pivotal role in the biogenesis of centrioles and regulation cell cycle. To date, mutation Cep135 has been reported to be closely associated with multiple morphological abnormalities flagella (MMAF) humans. However, specific mechanism spermatogenesis its detailed male infertility remains largely unexplored. In this study, we present compelling evidence that functions pathogenic gene responsible for oligoasthenoteratozoospermia (OAT) mice. By selectively deleting premeiotic germ cells using Stra8-Cre mice crossed Cep135flox/flox mice, observed knockdown produced abnormal sperm morphology, apoptosis consequentlybecame complete infertility, but did not impact premeiosis. Scanning transmission electron microscopy revealed defects acrosome, flagellum, head-to-tail connections during spermatogenesis. Proteomic analysis further indicated CEP135 deletion led significant reduction mainly acrosome formation, heads, flagellum microtubule assembly. Additionally, interacts spermatogenic SPATA6 AKAP3, regulating their expression stability. Deficiency or interacting resulted ciliary shortening. conclusion, our study profoundly unveils central fertility. This discovery only deepens comprehension also furnishes solid theoretical foundation experimental can guide formulation therapeutic preventive strategies infertility.

Language: Английский

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The Sperm‐Associated Antigen 11A (Spag11a) Knockout Mice Display Sub‐Fertility and Perturbations in the Sperm Proteome

Cell Biochemistry and Function, Journal Year: 2024, Volume and Issue: 42(7)

Published: Oct. 1, 2024

Spermatogenesis and sperm maturation that occur in the testis epididymis respectively are crucial for fertility. Factors secreted by testicular epididymal epithelial cells govern processes of gametogenesis maturation. Proteins encoded sperm-associated antigen 11a (Spag11a) gene implicated as having a possible role However, studies demonstrate their definite fertility function using knockout models have not yet reported. In this study, Spag11a mice were generated, genotyped reproductive parameters (fecundity, count, capacitation, acrosome reaction) proteome determined. Litter size count decreased when compared to wild-type controls. Spermatozoa from able undergo capacitation. reaction did obtained mice. Structural abnormalities head tail structures evident spermatozoa Perturbations expression proteins involved evident. The subfertility observed could be manifestation lower impaired reactions, disturbances proteome. results study lend further support male gamete function.

Language: Английский

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Homozygous deleterious variants in MYCBPAP induce asthenoteratozoospermia involving abnormal acrosome biogenesis, manchette structure and sperm tail assembly in humans and mice

Science China Life Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 18, 2024

Language: Английский

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