Deficiency of primate-specific TFDP3 causes male infertility with oligoasthenoteratozoospermia in humans and cynomolgus monkeys

KIZ OpenIR > 科研部门 > 鸟类学（杨晓君）

	Deficiency of primate-specific TFDP3 causes male infertility with oligoasthenoteratozoospermia in humans and cynomolgus monkeys
	Liu, CY; Tu, CF; Li, P; Wu, H; Wan, F; Lu, Y; Tang, SY; Li, X; Li, KK; Wang, JX; Gao, Y; Geng, XY; Meng, LL; Zhou, DP; Zhou, YL; Zhou, ZX; Guo, HB; Cao, YX; Jin, L; Li, Z; He, XJ; Tan, YQ; Sun, Q; Zhang, F
	2026
发表期刊	Sci. China-Life Sci.
ISSN	1674-7305
卷号	69 期号:5 页码:1594-1603
摘要	Primate-specific genes (PSGs), important contributors to the origin of adaptive evolutionary novelties, are abundantly expressed in the testis. However, the specific roles of PSGs in the male reproductive system of humans and other primates are largely unknown. Here, we employed whole-exome sequencing and identified deleterious variants of TFDP3, an X-linked PSG, in eight infertile men with oligoasthenoteratozoospermia. All of the male subjects harboring TFDP3 variants presented dramatic reductions in sperm concentration, motility, and abnormal sperm morphology. Furthermore, Tfdp3-knockdown (KD) in the testes of cynomolgus monkeys confirmed the important role of TFDP3 in normal spermatogenesis in primates. Consistently, dramatic decreases in sperm concentration, motility, and abnormal sperm morphology were also observed in Tfdp3-KD male cynomolgus monkeys. More importantly, further functional studies revealed that TFDP3 deficiency activated E2F1 induced apoptosis and thus led to decreased sperm count and motility. In addition, five of the eight couples underwent intra-cytoplasmic sperm injection treatment and achieved a successful pregnancy, indicating a potentially good outcome of assisted reproduction for those with TFDP3 deficiency-mediated oligoasthenoteratozoospermia. Collectively, our genetic analyses and experimental observations in humans and cynomolgus monkeys highlight the crucial role of TFDP3, an inhibitor of apoptosis, in normal spermatogenesis. These findings expand the spectrum of pathogenic variants for oligoasthenoteratozoospermia-associated male infertility and also reveal the special significance of primate-specific TFDP3 for the human male reproductive system, thus providing important guidance for genetic counseling and the clinical diagnosis of male infertility.
收录类别	SCIE
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/15125
专题	科研部门_鸟类学（杨晓君）
推荐引用方式 GB/T 7714	Liu, CY,Tu, CF,Li, P,et al. Deficiency of primate-specific TFDP3 causes male infertility with oligoasthenoteratozoospermia in humans and cynomolgus monkeys[J]. Sci. China-Life Sci.,2026,69(5):1594-1603.
APA	Liu, CY.,Tu, CF.,Li, P.,Wu, H.,Wan, F.,...&Zhang, F.(2026).Deficiency of primate-specific TFDP3 causes male infertility with oligoasthenoteratozoospermia in humans and cynomolgus monkeys.Sci. China-Life Sci.,69(5),1594-1603.
MLA	Liu, CY,et al."Deficiency of primate-specific TFDP3 causes male infertility with oligoasthenoteratozoospermia in humans and cynomolgus monkeys".Sci. China-Life Sci. 69.5(2026):1594-1603.

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