Neonatal DES exposure alters adult hepatic physiology

Hepatotoxicity induced by neonatal exposure to diethylstilbestrol is maintained throughout adulthood via the nuclear receptor SHP, 2014

Abstract

Background
Liver physiology is sensitive to estrogens, which suggests that the liver might be a target of estrogenic endocrine disrupters (EED). However, the long-term consequences of neonatal exposure to EED on liver physiology have rarely been studied. The nuclear receptor small heterodimer partner (SHP) mediates the deleterious effects of neonatal exposure to diethylstilbestrol (DES) on male fertility.

Objectives
As SHP is involved in liver homeostasis, we aimed to determine whether neonatal estrogenic exposure also affected adult liver physiology through SHP. Male mouse pups were exposed to DES in the first 5 days of life.

Results
DES exposure leads to alterations in the postnatal bile acid (BA) synthesis pathway. Neonatal DES-exposure affected adult liver BA metabolism and subsequently triglyceride (TG) homeostasis. The wild-type males neonatally exposed to DES exhibited increased liver weight and altered liver histology in the adult age. The use of deficient male mice revealed that SHP mediates the deleterious effects of DES treatment. These long-term effects of DES were associated with differently timed alterations in the expression of epigenetic factors.

Conclusions
However, the molecular mechanisms by which neonatal exposure persist to affect the adult liver physiology remain to be defined. In conclusion, we demonstrate that neonatal DES exposure alters adult hepatic physiology in an SHP-dependent manner.

Reference

  • Hepatotoxicity induced by neonatal exposure to diethylstilbestrol is maintained throughout adulthood via the nuclear receptor SHP, Expert opinion on therapeutic targets, NCBI PubMed, PMID: 6628266, 2014.
  • Featured image hepmag.
DES DIETHYLSTILBESTROL RESOURCES

2 Replies to “Neonatal DES exposure alters adult hepatic physiology”

  1. Why am I not surprised? High liver enzymes despite being on fairly strict keto for several years….affecting Blood sugars and abdominal fat…still……yet my Vanderbilt educated RN mother never remembered what the OB gave her for her ‘gestational hypothyroidism’ when she was carrying me in 1956….how convenient….she sure did remember that Golden child first born was exposed to DES….

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