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

During prenatal and early postnatal periods of development, multiple environmental factors have profound and long-lasting effects on the immune and reproductive functions. The aim of this study was to investigate the effects of maternal lipopolysaccharide (LPS) exposure (50 mg/kg, i.p.) at day 12 of pregnancy and estradiol antagonist treatment (fulvestrant, 1.5 mg/kg, s.c. in neck) at postnatal days 5-14 (PND5-14) with high estradiol levels on reproductive parameters in adult rat males. Serum steroid concentrations were measured in male offspring at PND80 by ELISA. Body, testis weights and ano-genital distance (AGD) were recorded at different stages of postnatal development. Testis was also processed to cytohistological studies at PND80. Our results demonstrate that body weight was decreased from PND14 to 30 after prenatal LPS treatment and was increased after fulvestrant treatment. AGD was decreased after prenatal LPS treatment and was increased after fulvestrant injections. Testis weight, testosterone level, seminiferous tubule diameter, and number of Sertoli and spermatid cells were also decreased in rats exposed prenatally to LPS and were restored to the normal control level after fulvestrant treatment. According to results, we can conclude that the development of sexual disorders in males after prenatal immune stress is potentiated by estradiol during the pre-pubertal period.

Lipopolysaccharide-induced maternal inflammation affects the gonadotropin-releasing hormone neuron development in fetal mice.

Recent studies provide evidence that prenatal immunological stress may affect the programming of reproductive health and sexual behavior in adult animals. The aim of this study was to investigate the influence of maternal inflammation, induced by an intraperitoneal (i.p.) injection of lipopolysaccharide (LPS, 45 µg/kg) on embryonic day 11.5 (E 11.5), on the development of the gonadotropin-releasing hormone (GnRH) system in mouse fetuses as well as on the proinflammatory cytokine level in pregnant mice and their fetuses. In the fetuses, the GnRH neuron migration from the olfactory pit to the forebrain was estimated on embryonic days 14.5 and 18.5. The levels of the proinflammatory cytokines interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-α and leukemia inhibitory factor (LIF) were measured with the cytometric bead and ELISA array method in the maternal and fetal blood, amniotic fluid and fetal cerebrospinal fluid (CSF). According to our data, activation of the immune system by LPS treatment on embryonic day 11.5 leads to an increased quantity of neurons in the nasal and olfactory bulb areas and a decreased quantity in the forebrain area on embryonic day 14.5. There was a slight decrease in the total number of neurons in the forebrain area on embryonic day 18.5. The levels of proinflammatory cytokines were significantly increased within 3 h after LPS treatment in the maternal and fetal blood, amniotic fluid and fetal CSF. IL-6-receptor immunoreactivity was detected on olfactory/vomeronasal axons. Thus, prenatal immunological stress delays the GnRH neuron migration in the nasal compartment of mouse fetuses, which may be mediated by the regulation of IL-6, MCP-1 and LIF secretion in the maternal-fetal system.