Neonatal lipopolysaccharide exposure impairs sexual development and reproductive success in the Wistar rat

Abstract

We investigated, in rats, whether neonatal exposure to bacterial lipopolysaccharide (LPS) impairs sexual development, sexual decline, and reproductive behaviour in later life. Rats were administered either LPS (Salmonella enterica, serotype enteritidis, 0.05mg/kg, ip) or saline (equivolume) on days 3 and 5 postpartum. The immediate and long-term effect of treatment on HPA and HPG hormones, testicular morphology, and mating behaviour was assessed. Neonatal LPS exposure induced a significant increase in corticosterone compared to controls, as well as reduced testosterone and LH in males and LH in females immediately following neonatal drug exposure. Neonatal LPS exposure disrupted the normal weight-to-age ratio of puberty onset in males and females, and impaired sexual performance in adulthood. Reproductive function was reflected in significantly diminished sperm presence in rats that had received neonatal LPS. LPS-treated females exhibited LH suppression during puberty, and males demonstrated testosterone suppression in late adulthood. Testosterone and LH surges during mating were significantly reduced in adult offspring treated with LPS as neonates. Furthermore, animals exposed to neonatal LPS and subsequent stress in adulthood, exhibited significantly blunted corticosterone responses. Morphometric assessment of testes taken from neonates revealed reduced gonocyte genesis immediately following LPS exposure and increased seminiferous disorganisation of the epithelium in these animals in adulthood. This research demonstrates the long-term impact of neonatal bacterial exposure on reproductive success given that early life exposure to bacteria disrupted puberty onset and sexual performance. Associated changes in neuroendocrine functioning suggest a possible mechanism through which a subfertile phenotype may arise.