Behavioral Alterations in Response to Fear-Provoking Stimuli and Tranylcypromine Induced by Perinatal Exposure to Bisphenol A and Nonylphenol in Male Rats

Abstract Perinatal exposure to environmental levels of bisphenol-A (BPA) impairs sexually dimorphic behaviors in rodents. Kisspeptin neurons in anteroventral periventricular nucleus (AVPV), which plays an important role in the activation of GnRH neurons and the initiation of LH-surge, have been suggested to be sexual dimorphism in rats. This study focused on exploring the influence of a perinatal exposure to an environmental dose of BPA on the development and maturation of male AVPV kisspeptin neurons and hypothalamus-pituitary-gonadal axis. Female rats were injected sc with 2 μg BPA/kg·d from gestation d 10 through lactation d 7. Anatomical and functional changes in AVPV kisspeptin neurons and hypothalamus-pituitary-gonadal axis were examined in prepubertal, pubertal, and adult male rats exposed perinatally to BPA (BPA-rats). Here, we show that in postnatal d (PND)30/50/90 BPA-rats, the number of AVPV kisspeptin-immunoreactive cells was persistently increased in comparison with age-matched control male rats. The number of GnRH-immunoreactive cells in PND30 BPA-rats declined approximately 40% compared with control male rats, whereas that in PND50/90 BPA-rats was increased in a G protein-coupled receptor 54-dependent manner. Estradiol could induce a stable LH-surge in PND90 BPA-rats and control female rats, which was sensitive to the G protein-coupled receptor 54 inhibitor. In PND30/50 BPA-rats, plasma level of LH was higher, but the level of testosterone was lower than control male rats. These findings provide evidence that perinatal exposure to an environmental dose of BPA causes a sustained increase in AVPV kisspeptin neurons in male rats, leading to the generation of estradiol-induced LH-surge system.

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Perinatal exposure to a low dose of bisphenol-A advances pubertal spermatogenesis of F1 adolescent male rats

10.21203/rs.3.rs-72109/v1 ◽

2020 ◽

Author(s):

Yinyang Bai ◽

Fang Xiong ◽

Yun Zhang ◽

Jie Chen ◽

Lishuang Xu ◽

...

Keyword(s):

Bisphenol A ◽

Plasma Levels ◽

Low Dose ◽

Male Offspring ◽

Female Rats ◽

Male Rats ◽

Seminiferous Tubules ◽

Perinatal Exposure ◽

Significant Difference ◽

The Impact

Abstract Background To investigate the impact of perinatal exposure to a low dose of bisphenol A (BPA) on spermatogenesis in male rats and the underlying mechanism. Methods Female rats were injected subcutaneously with 2 µg BPA/kg/day from gestation day 10 through lactation day 7. The spermatogenesis and expression of key regulatory genes in the testes as well as the central modulators of the hypothalamic-pituitary-gonadal axis were determined in male offspring on postnatal day 18, 21, and 24 (PND18, 21, and 24). Results 1) Perinatal BPA exposure led to an increase in the weight of body and testis in PND21-24 male offspring. The seminiferous tubular diameter and the number of round spermatids were significantly increased in PND21 BPA-rats, while the volumes of the Sertoli cells, spermatogonia and spermatocytes were not significantly altered. 2) Compared to the control rats, the expression levels of key meiotic regulators such as cyclinA1, c-jun and c-fos in the seminiferous tubules were significantly elevated in PND21 BPA-rats. 3) The plasma levels of FSH and LH (PND21 and PND24) as well as the frequency of pulsatile LH secretion (PND21) were significantly increased in BPA-rats, although the plasma levels of testosterone and estrogen showed no significant difference between the two groups. 4) In comparison with control rats, the levels of GnRH mRNA in the preoptic area (POA) and kiss1 mRNA in arcuate nucleus (ARC) were significantly increased in the BPA-rats, whereas the level of ERα mRNA in ARC was decreased, although the number of GnRH-positive cells and ARC kisspeptin-positive cells were unchanged. Interestingly, neither the number of kisspeptin-positive cells nor the level of kiss1 mRNA in the anteroventral periventricular nucleus (AVPV) showed a difference between the two groups. Conclusion Perinatal exposed to a low dose of BPA leads to an increased meiosis of spermatocytes and promotes the spermatogenesis in male offspring, most likely through activation of the hypothalamic-pituitary-gonadal axis.

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