Impact of 4-Methylbenzylidene-camphor (4-MBC) during Embryonic and Fetal Development in the Neuroendocrine Regulation of Testicular Axis in Prepubertal and Peripubertal Male Rats

Abstract

4-Methylbenzylidene-camphor (4-MBC), an UV-B ray filter, belongs to the endocrine disrupters involved with alterations in the reproductive axis. Our target was to study the effect of 4-MBC on the neuroendocrine parameters that regulate reproduction in prepubertal and peripubertal male rats, which received this disrupter during embryonic and fetal development. 4-MBC was administered (sc) to female rats since pregnancy onset in doses of 20, 100 and 500 mg/kg/day. The litters were sacrificed at 15 or 30 days old to determine testicular weight, gonadotropin and prolactin serum levels and also GnRH and amino acids release from the hypothalamus. The exposure to 20 mg/kg/day only increased the LH serum levels in 30-day-old males. Doses of 100 and 500 mg/kg/day caused a decrease in testicular weight and in LH, GnRH and glutamate levels, in prepubertal rats (15-day-old specimens), and an increase in, gonadotropin (LH and FSH) con-centration and aspartate levels in peripubertal rats (30-day-old specimens), without changes in testicular weight. Prolactinaemia remained unaltered in all groups. Results obtained show that the administration of high doses of 4-MBC during embryonic and fetal stage inhibits the testicular axis in male rats during the prepubertal stage and stimulates it during peripubertad stage. On the other hand in the case of low doses no significant effects were observed.

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“…Subcutaneous administration of high dosages (up to 500 mg/kg/day) during pregnancy and lactation altered the hypothalamic secretion of excitatory amino acids Glu and Asp in male offspring. These neurotransmitters play a role as stimulators of gonadal axis, thus the observed changes are consistent with alterations in sexual development of male offspring, affecting pre-pubertal stage, but stimulating the peri-pubertal stage [56] . In addition, 4-MBC has been reported to have an acetylcholinesterase (AChE) inhibitory activity.…”

“…Inhibited testicular axis in male offspring during the pre-pubertal stage and stimulated during peri-pubertal stage. [56] Danio rerio Embryos exposed in medium 68 h 1–50 μM Inhibited AChE activity, impaired early muscular and neuronal development. [57] Neuro-2a mouse neuroblastoma cell line 45 min 0.1–100 μM Inhibited AChE activity.…”

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“…Thus, it has been shown that exposure to MBC in developing rats affects the regulation of target estrogen gene (Mueller et al 2003;Durrer et al 2005;, interferes in a specific way with sexual gene expression in the brain (Maerkel et al 2005;Maerkel et al 2007;Carou et al 2008;Carou et al 2009a;Carou et al 2009b), influences the development of organs and the reproductive functions in males (Durrer et al 2007;Hofkamp et al 2008) and even promotes the growth of the prostate .…”

Stoffmonographie für 3-(4-Methylbenzyliden)-kampfer (4-MBC) – HBM-Werte für die Summe der Metaboliten 3-(4-Carboxybenzyliden)-kampfer (3-4CBC) und 3-(4-Carboxybenzyliden)-6-Hydroxykampfer (3-4CBHC) im Urin von Erwachsenen und Kindern

“…In einer weiteren Studie an ovarektomierten Ratten wurden bei ähn-lich hohen Dosen ein erhöhter TSH-und ein erniedrigter T4-Spiegel sowie ein uneinheitlicher, nicht dosisabhängiger Effekt auf den T3-Spiegel festgestellt [42]. Subkutane Verabreichung von 2-20 mg/ (kg KG · d) an weibliche Ratten stimulierte die Freisetzung von FSH, LH und GnRH [43]; die subkutane Verabreichung von 20-500 mg/(kg KG · d) an trächtige Ratten beeinflusste das Hodengewicht sowie die Gonadotropinfreisetzung aus dem Hypothalamus [44,45]. In einer anderen Untersuchung zeigte 4-MBC nach einmaliger oraler Gabe von 500 bzw.…”