Insulin-Like Growth Factor 1 Is Expressed in Mouse Developing Testis and Regulates Somatic Cell Proliferation

Villalpando, Irma; Lira-Romero, Esmeralda; Medina, Georgina; García‐García, Erick; Echeverría, Olga M.

doi:10.3181/0708-rm-212

Cited by 32 publications

(21 citation statements)

References 37 publications

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“…In mammals, Igf ligands can reach the testes from extratesticular sites via the circulation but can also be derived from different testicular cell types, such as Sertoli and Leydig cells in mice (61) or different germ cell types in stallion (62). Both somatic (Leydig and Sertoli cells) and germ cells (mainly spermatogonia and spermatocytes) have been identified as Igf1 sources also in fish (57,58,63,64).…”

Section: Discussionmentioning

confidence: 97%

Fsh Stimulates Spermatogonial Proliferation and Differentiation in Zebrafish via Igf3

et al. 2015

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Growth factors modulate germ line stem cell self-renewal and differentiation behavior. We investigate the effects of Igf3, a fish-specific member of the igf family. Fsh increased in a steroid-independent manner the number and mitotic index of single type A undifferentiated spermatogonia and of clones of type A differentiating spermatogonia in adult zebrafish testis. All 4 igf gene family members in zebrafish are expressed in the testis but in tissue culture only igf3 transcript levels increased in response to recombinant zebrafish Fsh. This occurred in a cAMP/protein kinase A-dependent manner, in line with the results of studies on the igf3 gene promoter. Igf3 protein was detected in Sertoli cells. Recombinant zebrafish Igf3 increased the mitotic index of type A undifferentiated and type A differentiating spermatogonia and up-regulated the expression of genes related to spermatogonial differentiation and entry into meiosis, but Igf3 did not modulate testicular androgen release. An Igf receptor inhibitor blocked these effects of Igf3. Importantly, the Igf receptor inhibitor also blocked Fsh-induced spermatogonial proliferation. We conclude that Fsh stimulated Sertoli cell production of Igf3, which promoted via Igf receptor signaling spermatogonial proliferation and differentiation and their entry into meiosis. Because previous work showed that Fsh also released spermatogonia from an inhibitory signal by down-regulating anti-Müllerian hormone and by stimulating androgen production, we can now present a model, in which Fsh orchestrates the activity of stimulatory (Igf3, androgens) and inhibitory (anti-Müllerian hormone) signals to promote spermatogenesis.

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Section: Discussionmentioning

confidence: 97%

Fsh Stimulates Spermatogonial Proliferation and Differentiation in Zebrafish via Igf3

et al. 2015

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“…In addition to the systemic role of IGF-I, it also has important autocrine and paracrine roles at the cellular level, regulating mitosis, apoptosis, and cellular differentiation. The testes are clearly a site of IGF-I biosynthesis and action (Wang and Hardy, 2004); LH stimulates IGF-I secretion in rodent testes (Cailleau et al, 1990) and both IGF-I and its receptors have been detected in Leydig cells, Sertoli cells, and spermatocytes in various species (Hansson et al, 1989;Villalpando et al, 2008). Wang and Hardy (2004) evaluated a target gene deletion of IGF-I in the testes and concluded that both IGF-I and LH are critical factors in determining Leydig cell numbers and their steroidogenic capacity (Wang and Hardy, 2004).…”

Section: Discussionmentioning

confidence: 98%

Enhanced early-life nutrition promotes hormone production and reproductive development in Holstein bulls

Dance

Thundathil

Wilde

et al. 2015

Journal of Dairy Science

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Holstein bull calves often reach artificial insemination centers in suboptimal body condition. Early-life nutrition is reported to increase reproductive performance in beef bulls. The objective was to determine whether early-life nutrition in Holstein bulls had effects similar to those reported in beef bulls. Twenty-six Holstein bull calves were randomly allocated into 3 groups at approximately 1 wk of age to receive a low-, medium-, or high-nutrition diet, based on levels of energy and protein, from 2 to 31 wk of age. Calves were on their respective diets until 31 wk of age, after which they were all fed a medium-nutrition diet. To evaluate secretion profiles and concentrations of blood hormones, a subset of bulls was subjected to intensive blood sampling every 4 wk from 11 to 31 wk of age. Testes of all bulls were measured once a month; once scrotal circumference reached 26cm, semen collection was attempted (by electroejaculation) every 2 wk to confirm puberty. Bulls were maintained until approximately 72 wk of age and then slaughtered at a local abattoir. Testes were recovered and weighed. Bulls fed the high-nutrition diet were younger at puberty (high=324.3 d, low=369.3 d) and had larger testes for the entire experimental period than bulls fed the low-nutrition diet. Bulls fed the high-nutrition diet also had an earlier and more substantial early rise in LH than those fed the low-nutrition diet and had increased concentrations of insulin-like growth factor-I (IGF-I) earlier than the bulls fed the low-nutrition diet. Furthermore, we detected a temporal association between increased IGF-I concentrations and an early LH rise in bulls fed the high-nutrition diet. Therefore, we inferred that IGF-I had a role in regulating the early gonadotropin rise (in particular, LH) and thus reproductive development of Holstein bulls. Overall, these results support our hypothesis that Holstein bull calves fed a high-nutrition diet reach puberty earlier and have larger testes than those fed a low-nutrition diet, and they provide clear evidence that nutritional modulation of Holstein bull calves during early life has profound effects on reproductive development.

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“…Igf1 and Igf1r are expressed in Sertoli and Leydig cells from E12-E18 during mouse development, with highest levels of both proteins detected at E18 [52]. Increased expression of the IGF1R was detected in adult Irs2 -deficient testes (Fig.…”

Section: Discussionmentioning

confidence: 86%

Insulin Receptor Substrate 2 Is Required for Testicular Development

2013

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Insulin receptor substrate (IRS) proteins are key mediators of insulin and insulin-like growth factor (IGF) signalling. In mice, deletion of Irs1 is associated with profound growth retardation and increased longevity whereas Irs2-deficiency causes diabetes and female infertility. Clinical studies suggest that diabetes and obesity diminish male fertility. However, the role of IRS proteins in male reproduction is unknown. We observed that testis weight is reduced by 45% in Irs2-deficient mice as compared with control males. The weight of these organs in Irs1 −/− males was similar to controls; however, since Irs1-deficient mice are 50% smaller, testis weight:body weight was increased in this model. Neonatal Irs2 −/− mice also exhibited reduced testicular size, suggesting that impairments in this model occur during development. Histological examination of testicular cross sections from Irs2 −/− mice revealed normal cellular associations without obvious abnormalities in the seminiferous epithelium. Reduced testicular weight was associated with fewer Sertoli cells, spermatogonia, spermatocytes, elongated spermatids, and epididymal spermatozoa. However, Leydig cell number and the concentration of serum testosterone were equivalent between Irs2-deficient and control males. Testicular weight was reduced similarly in non-diabetic and diabetic Irs2 −/− mice, indicating that hyperglycemia does not compound the effects of Irs2 deletion on impaired testis development. Expression of Irs1, Irs3, and Irs4 was comparable between experimental groups. Collectively, our results demonstrate that IRS2 plays a critical role in testicular development, potentially by mediating IGF1 signalling during embryonic and early postnatal development.

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Insulin-Like Growth Factor 1 Is Expressed in Mouse Developing Testis and Regulates Somatic Cell Proliferation

Cited by 32 publications

References 37 publications

Fsh Stimulates Spermatogonial Proliferation and Differentiation in Zebrafish via Igf3

Fsh Stimulates Spermatogonial Proliferation and Differentiation in Zebrafish via Igf3

Enhanced early-life nutrition promotes hormone production and reproductive development in Holstein bulls

Insulin Receptor Substrate 2 Is Required for Testicular Development

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