Prenatal Dexamethasone Exposure Induced Ovarian Developmental Toxicity and Transgenerational Effect in Rat Offspring.

Abstract:

:Prenatal dexamethasone exposure (PDE) induces multiorgan developmental toxicities in offspring. Here we verified the transgenerational inheritance effect of ovarian developmental toxicity by PDE and explored its intrauterine programming mechanism. Pregnant rats subcutaneously received 0.2 mg/kg/d dexamethasone from gestational day (GD) 9 to GD20. A subgroup was euthanized for fetuses on GD20, and the other group went on to spontaneous labor to produce F1 offspring. The adult F1 females were mated with normal males to produce the F2 and F3 generations. The PDE fetal rats exhibited ovarian mitochondrial structural abnormalities, decreased serum estradiol (E2) levels, and lower expression levels of ovarian steroidogenic factor 1 (SF1), steroidal synthetases, and insulinlike growth factor 1 (IGF1). On postnatal week (PW) 6 and PW12, the PDE F1 offspring showed altered reproductive behavior and ovarian morphology. The serum E2 level and ovarian expression of SF1, steroidal synthetases, and IGF1 were also decreased. The adult F3 offspring showed alterations in reproductive phenotype and ovarian IGF1, SF1, and steroidal synthetase expression similar to those of F1. PDE induces ovarian developmental toxicity and transgenerational inheritance effects. The mechanism by which this toxicity occurs may be related to PDE-induced low-functional programming of fetal ovarian IGF1/SF1 and steroidal synthetases.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Lv F,Wan Y,Chen Y,Pei L,Luo D,Fan G,Luo M,Xu D,Wang H

doi

10.1210/en.2018-00044

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

1401-1415

issue

3

eissn

0013-7227

issn

1945-7170

pii

4822184

journal_volume

159

pub_type

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