A Critical Point of Male Gonad Development: Neuroendocrine Correlates of Accelerated Testicular Growth in Rats during Early Life

Abstract

Testis growth during early life is important for future male fertility and shows acceleration during the first months of life in humans. This acceleration coincides with the peak in gonadotropic hormones in the blood, while the role of hypothalamic factors remains vague. Using neonatal rats to assess this issue, we found that day 9 of life is likely critical for testis development in rats. Before this day, testicular growth was proportional to body weight gain, but after that the testes showed accelerated growth. Hypothalamic kisspeptin and its receptor mRNA levels begin to elevate 2 days later, at day 11. A significant increase in the mRNA levels for gonadotropin-releasing hormone (GnRH) receptors in the hypothalamus between days 5 and 7 was followed by a 3-fold decrease in GnRH mRNA levels in this brain region during the next 2 days. Starting from day 9, hypothalamic GnRH mRNA levels increased significantly and positively correlated with accelerated testicular growth. Triptorelin, an agonist of GnRH, at a dose that had no effect on testicular growth during “proportional” period, increased testis weights during the period of accelerated growth. The insensitivity of testicular growth to GnRH during “proportional” period was supported by inability of a 2.5-fold siRNA knockdown of GnRH expression in the hypothalamus of the 7-day-old animals to produce any effect on their testis weights. GnRH receptor blockade with cetrorelix was also without effect on testis weights during “proportional” period but the same doses of this GnRH antagonist significantly inhibited “accelerated” testicular growth. GnRH receptor mRNA levels in the pituitary as well as plasma LH concentrations were higher during “accelerated” period of testicular growth than during “proportional” period. In general, our data defined two distinct periods in rat testicular development that are primarily characterized by different responses to GnRH signaling.

Abolition of prenatal lipopolysaccharide-induced reproductive disorders in rat male offspring by fulvestrant

“…However, the development of testis is not completed within the prenatal period and continues after birth, their growth undergoes acceleration in rats after PND9 (Dygalo, Shemenkova, Kalinina, & Shishkina, ). Testis development becomes sensitive to hypothalamic regulation by GnRH and kisspeptin between PND9 and PND14 (Dygalo et al, ).…”

“…However, the development of testis is not completed within the prenatal period and continues after birth, their growth undergoes acceleration in rats after PND9 (Dygalo, Shemenkova, Kalinina, & Shishkina, ). Testis development becomes sensitive to hypothalamic regulation by GnRH and kisspeptin between PND9 and PND14 (Dygalo et al, ). In early postnatal period (up to PND15), foetal gonocytes become mitotically active spermatogonia cells, Sertoli cells enhance the mitosis rate and maturation, and foetal Leydig cells begin to replace by adult Leydig cells (Picut et al, ).…”

The effect of chronic stress on the testis of adult albino Rats and the possible protective effect of astaxanthin supplementation (Histological, immunohistochemical and biochemical studies)

“…Relative testicular weights: were determined by dissecting both testes and then weight them to obtain the absolute weight. The relative testicular weight was calculated in percentage of average absolute testicular weight/ body weight [23] .…”

Maternal CBZ exposure impairs testicular development, spermatogenesis and sperm parameters in male offspring at puberty

“…In the neonatal phase, from birth to approximately 6th GD, the testis growth is due to an increase in the tubular length and related to the proliferation of Sertoli cells (Dygalo, Shemenkova, Kalinina, & Shishkina, 2014; Gaytan, Lucena, Munoz, & Paniagua, 1986; Walker, 2003). On the other hand, the increase in tubular diameter would be directly related to the onset, progression and maintenance of the spermatogenic process on the 8th and 10th PND (Roosen‐Runge & Leik, 1968).…”