Prepubertal nutrition alters Leydig cell functional capacity and timing of puberty

Abstract

Leydig cell functional capacity reflects the numbers and differentiation status of the steroidogenic Leydig cells in the testes and becomes more or less fixed in early adulthood with the final establishment of the hypothalamo-pituitary-gonadal (HPG) axis after puberty. Factors influencing Leydig cell functional capacity and its role in puberty are poorly understood. Using a bovine model of dairy bulls fed four different nutritional regimes from 1 month to 12 months, and applying circulating Insulin-like peptide 3 (INSL3) as an accurate biomarker of Leydig cell functional capacity, showed that a high plane of nutrition in the first 6 months of life, but not later, significantly increased INSL3 in young adulthood. Moreover, INSL3 concentration at 4 months indicated a marked differential in early feeding regime and correlated well (negatively) with the timing of puberty, as reflected by the age in days for the first production of an ejaculate with >50 million sperm and >10% forward motility, as well as with testis size at 18 months. Reversing the diet at 6 months was unable to rectify the trend in either parameter, unlike for other parameters such as testosterone, body weight, and scrotal circumference. This study has shown that early prepubertal nutrition is a key factor in the development of Leydig cell functional capacity in early adulthood and appears to be a key driver in the dynamic progression of puberty.

Effect of plane of nutrition during the first 12 weeks of life on growth, metabolic and reproductive hormone concentrations, and testicular relative mRNA abundance in preweaned Holstein Friesian bull calves

“…Insulin-like 3 (INSL3) is a major secretory product of testicular Leydig cells ( Hannan et al, 2015 ) and serves as an excellent marker for Leydig cell differentiation and functional capacity during sexual development of cattle ( Ivell et al, 2014 ). In agreement, another recent study from our group showed that a high plane of nutrition in the first 6 mo of life, but not later, increased systemic concentrations of INSL3 in young bulls ( Anand-Ivell et al, 2019 ). Moreover, in that study, INSL3 concentration at 4 mo of age correlated well (negatively) with the timing of puberty, as well as with testis size at 18 mo ( Anand-Ivell et al, 2019 ).…”

“…In agreement, another recent study from our group showed that a high plane of nutrition in the first 6 mo of life, but not later, increased systemic concentrations of INSL3 in young bulls ( Anand-Ivell et al, 2019 ). Moreover, in that study, INSL3 concentration at 4 mo of age correlated well (negatively) with the timing of puberty, as well as with testis size at 18 mo ( Anand-Ivell et al, 2019 ). In agreement, Sakase et al (2018) found that blood INSL3 concentrations may be a robust and repeatable biomarker for determining total testicular volume and degree of sexual maturity in prepubertal bull calves.…”

Male seminal parameters are not associated with Leydig cell functional capacity in men

“…How BMI affects circulating INSL3 levels is not known, but unlike for testosterone where the increased levels of aromatase in fat tissue will have a directly modifying effect on the circulating androgen, it appears more likely that adipose tissue factors may be influencing Leydig cell function. Moreover, a recent study in bulls has shown a positive effect of a prepubertal high‐protein diet on both later INSL3 production and the timing of puberty 47 . Together, such results support a view that healthy prepubertal nutrition may positively influence chronic adult Leydig cell functional capacity, though a negative influence of other environmental and lifestyle stressors cannot be excluded.…”

“…Moreover, a recent study in bulls has shown a positive effect of a prepubertal high-protein diet on both later INSL3 production and the timing of puberty. 47 Together, such results support a view that healthy prepubertal nutrition may positively influence chronic adult Leydig cell functional capacity, though a negative influence of other environmental and lifestyle stressors cannot be excluded. Numerous viruses have been detected in human semen.…”

Growing Up Under Constant Light: A Challenge to the Endocrine Function of the Leydig Cells

“…In male life, two populations of Leydig cells exist. Fetal Leydig cells produce androgens and INSL3 in embryonic life crucial for the male fetus’s masculinization ( 5 , 6 ). Androgenic activity of the fetal Leydig cells continues for a few weeks after birth, and after that, they disappear, followed by hormonal quiescence until puberty.…”