Maternal LPS Exposure during Pregnancy Impairs Testicular Development, Steroidogenesis and Spermatogenesis in Male Offspring

Abstract

Lipopolysaccharide (LPS) is associated with adverse developmental outcomes including embryonic resorption, fetal death, congenital teratogenesis and fetal growth retardation. Here, we explored the effects of maternal LPS exposure during pregnancy on testicular development, steroidogenesis and spermatogenesis in male offspring. The pregnant mice were intraperitoneally injected with LPS (50 µg/kg) daily from gestational day (GD) 13 to GD 17. At fetal period, a significant decrease in body weight and abnormal Leydig cell aggregations were observed in males whose mothers were exposed to LPS during pregnancy. At postnatal day (PND) 26, anogenital distance (AGD), a sensitive index of altered androgen action, was markedly reduced in male pups whose mothers were exposed to LPS daily from GD13 to GD 17. At PND35, the weight of testes, prostates and seminal vesicles, and serum testosterone (T) level were significantly decreased in LPS-treated male pups. At adulthood, the number of sperm was significantly decreased in male offspring whose mothers were exposed to LPS on GD 13–17. Maternal LPS exposure during gestation obviously diminished the percent of seminiferous tubules in stages I–VI, increased the percent of seminiferous tubules in stages IX–XII, and caused massive sloughing of germ cells in seminiferous tubules in mouse testes. Moreover, maternal LPS exposure significantly reduced serum T level in male mice whose mothers were exposed to LPS challenge during pregnancy. Taken together, these results suggest that maternal LPS exposure during pregnancy disrupts T production. The decreased T synthesis might be associated with LPS-induced impairments for spermatogenesis in male offspring.

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

“…Animal model studies have identified that AGD may provide the means for retrospectively determining foetal androgen exposure during masculinisation and male reproductive tract development (van den Driesche, Kolovos, Platts, Drake, & Sharpe, ; Welsh, ). AGD decreased in male mice at PND26 after maternal LPS treatment from E13 to E17 (Wang et al, ). AGD in newborn boys as well as adult men reflects the reproductive status (Dean & Sharpe, ).…”

“…Previous studies provide evidence that exposure to LPS in early development resulted in reduced sexual behaviour, spermatogenesis and serum concentration of luteinising hormone (LH) and testosterone in rat and mouse offspring (Izvolskaia et al, ; Solati, Hajikhani, Rashidieh, & Jalilian, ; Wang et al, ).…”

“…The second group was injected i.p with LPS ( E. coli , Sigma; 50 µg/kg body) in the same volume at the same time and day of pregnancy (LPS‐treated group, 14 rats). LPS concentration was chosen according to previously published data (Sharova et al, ; Wang et al, ).…”

Factors in Early-Life Programming of Reproductive Fitness

“…In the same model, LH and FSH suppression was observed at puberty in females [13,14], and suppression of testosterone and LH surges was observed in both sexes during mating [14]. Similarly, LPS exposure during gestation induced a decline in circulating testosterone levels in pubertal male offspring [67]. Moreover, in late adulthood, neonatally LPS-treated males have been reported to exhibit decreased testosterone levels [14], while adult females had lower circulating progesterone levels and a tendency to increased testosterone levels [68].…”

“…These changes have been associated with decreased circulating testosterone [14,67], as well as abnormal aggregation of Leydig (testosterone producing) cells in foetal testes [67]. It is quite plausible that perinatal LPS challenge disrupts testosterone synthesis, leading to long-term changes in gonadal morphology and function.…”