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Endocrinology. 2018 Mar 1;159(3):1401-1415. doi: 10.1210/en.2018-00044.

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

Lv F1, Wan Y1, Chen Y1, Pei L1, Luo D2, Fan G1, Luo M2, Xu D1,2, Wang H1,2.

Author information

1
Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
2
Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China.

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.

PMID:
29370380
DOI:
10.1210/en.2018-00044
[Indexed for MEDLINE]

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