Insulin growth factors may be implicated in human sperm capacitation

Sánchez-Luengo, Silvia; Fernández, Pascual; Romeu, A.

doi:10.1016/j.fertnstert.2004.12.003

Cited by 26 publications

(22 citation statements)

References 11 publications

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“…IGF1R has been found in seminal plasma from fertile and infertile men. However, defective expression of IGF1R was observed in sperm from patients with a history of failed fertilization (48). It is possible that there might be defective hyperactive motility and tyrosine phosphorylation mediated by IGF1R during sperm capacitation in these sperm.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Phosphoproteomics Analysis Reveals a Key Role of Insulin Growth Factor 1 Receptor (IGF1R) Tyrosine Kinase in Human Sperm Capacitation*

Wang

Lin

Huang

et al. 2015

Molecular & Cellular Proteomics

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One of the most important changes during sperm capacitation is the enhancement of tyrosine phosphorylation. However, the mechanisms of protein tyrosine phosphorylation during sperm capacitation are not well studied. We used label-free quantitative phosphoproteomics to investigate the overall phosphorylation events during sperm capacitation in humans and identified 231 sites with increased phosphorylation levels. Motif analysis using the NetworKIN algorithm revealed that the activity of tyrosine phosphorylation kinases insulin growth factor 1 receptor (IGF1R)/insulin receptor is significantly enriched among the up-regulated phosphorylation substrates during capacitation. Western blotting further confirmed inhibition of IGF1R with inhibitors GSK1904529A and NVP-AEW541, which inhibited the increase in tyrosine phosphorylation levels during sperm capacitation. Additionally, sperm hyperactivated motility was also inhibited by GSK1904529A and NVP-AEW541 but could be up-regulated by insulin growth factor 1, the ligand of IGF1R. Thus, the IGF1R-mediated tyrosine phosphorylation pathway may play important roles in the regulation of sperm capacitation in humans and could be a target for improvement in sperm functions in infertile men. Molecular & Cellular Proteomics 14: 10.1074/mcp.M114.045468, 1104-1112, 2015.Austin (1) and Chang (2) discovered that sperm must reside in the female genital tract for a specific period of time to acquire the ability to fertilize an egg and named this process "capacitation." During capacitation, several biochemical changes occur, including enhancement of tyrosine phosphorylation (3), increased intracellular Ca 2ϩ and cAMP levels (4), hyperactivated motility (5), and increased membrane plasma permeability (6). Mature sperm are highly differentiated and specialized cells, there is almost no transcription, and the genomic ribosome is inactive (5). Therefore, regulation of proteins at the level of post-translational modification is expected to play important roles in sperm functions. In mammalian sperm, phosphorylated proteins, protein kinases, and phosphatases are reported to function in sperm motility, capacitation, and acrosome reaction (7, 8). Tyrosine phosphorylation and dephosphorylation are required for sperm to reach, bind, penetrate, and fuse with the oocyte (5). Tyrosinephosphorylated proteins have been found in human (9), monkey (10), rat (11), and mouse (12) sperm. The sperm tail is the main location of protein tyrosine phosphorylation, and tyrosine phosphorylation of the sperm tail is related to hyperactivated motility (13). However, the mechanism of protein tyrosine phosphorylation regulation in sperm capacitation is not well studied. With high throughput ability, proteomics has been used to characterize phosphorylation in sperm. For the human sperm, Ficarro et al. (14) used two-dimensional polyacrylamide gel electrophoresis (PAGE), anti-phosphotyrosine antibody labeling, and tandem mass spectrometry (MS/MS) to identify tyrosine phosphoproteins during capacitation. They identified...

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Section: Discussionmentioning

confidence: 99%

Quantitative Phosphoproteomics Analysis Reveals a Key Role of Insulin Growth Factor 1 Receptor (IGF1R) Tyrosine Kinase in Human Sperm Capacitation*

Wang

Lin

Huang

et al. 2015

Molecular & Cellular Proteomics

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“…Previous studies have investigated the role of IGF-I in sperm function, semen quality, and infertility in terms of a mitogenic, metabolic, and differentiating polypeptide with endocrine, paracrine, and autocrine effects (Henricks et al, 1998;Sanchez-Luengo et al, 2005;Puche & Castilla-Cortazar, 2012). Prior animal studies have provided more details on the role of IGF-I in spermatogenesis and semen quality and it was shown that the proportion of normal sperm cells was related to blood (Yilmaz et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…In humans, locally produced factors such as IGF-I are important regulators of human testicular function (Ovesen et al, 1995;Puche & Castilla-Cortazar, 2012); IGF-I is essential for fertilization (Sanchez-Luengo et al, 2005) and its seminal level is correlated with semen quality and maturation of spermatozoa (Glander et al, 1996).…”

Section: Igf-i Concentration In Bullsmentioning

confidence: 99%

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Seminal insulin-like growth factor-I may be involved in the pathophysiology of infertility among patients with clinical varicocele

et al. 2014

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Varicocele, the most common cause of male infertility, is defined as abnormal dilation of the pampiniform plexus. Although different mechanisms have been proposed to explain the pathophysiology of infertility caused by varicocele, it is still open to debate. Previous studies have demonstrated the effect of insulin-like growth factor-I (IGF-I) on semen quality in animals and humans, but there are no studies on the probable role of seminal IGF-I in the pathophysiology of infertility among patients with clinical varicocele. We therefore aimed to examine the seminal IGF-I concentration in 49 patients with varicocele and primary infertility before and after varicocelectomy and compare the results with those of 50 healthy fertile men (in the control group). Mean seminal IGF-I level of patients before varicocelectomy (93.7 ± 67.2 ng/mL) was significantly different (P < 0.001) from that following varicocelectomy (58 ± 35.1 ng/mL) and from that of the controls (57.6 ± 22.1 ng/mL). However, mean seminal IGF-I levels of patients after varicocelectomy and the controls were not significantly different. Seminal IGF-I level was not correlated with grade and side of varicocele, and semen quality. We conclude that locally secreted IGF-I in the semen may be involved in the pathophysiology of infertility in patients with varicocele or semen.

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“…The in vitro effects of IGF-1 on bovine sperms have been observed to significantly improve the total and progressive motility of bovine sperm [10]. In addition, IGF-I also plays a role in human sperm maturation and capacitation [14]; it prevents the deterioration of sperm functional parameters and fertility in buffaloes [15] and increases sperm motility and viability in rabbits [16] and bulls [10].…”

Section: Introductionmentioning

confidence: 99%

Insulinlike growth factor I improves yak (Bos grunniens) spermatozoa motility and the oocyte cleavage rate by modulating the expression of Bax and Bcl-2

et al. 2015

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Insulin growth factors may be implicated in human sperm capacitation

Cited by 26 publications

References 11 publications

Quantitative Phosphoproteomics Analysis Reveals a Key Role of Insulin Growth Factor 1 Receptor (IGF1R) Tyrosine Kinase in Human Sperm Capacitation*

Quantitative Phosphoproteomics Analysis Reveals a Key Role of Insulin Growth Factor 1 Receptor (IGF1R) Tyrosine Kinase in Human Sperm Capacitation*

Seminal insulin-like growth factor-I may be involved in the pathophysiology of infertility among patients with clinical varicocele

Insulinlike growth factor I improves yak (Bos grunniens) spermatozoa motility and the oocyte cleavage rate by modulating the expression of Bax and Bcl-2

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