Maternal protein restriction during gestation and lactation programs offspring ovarian steroidogenesis and folliculogenesis in the prepubertal gilts.
Maternal malnutrition may disrupt ovarian functions in adult offspring. Steroidogenesis and folliculogenesis in the offspring ovary appear to be the major targets of nutritional programming. Nevertheless, the mechanism by which maternal low-protein diet affects the offspring steroidogenesis and folliculogenesis, and the possible pathway linking these two processes remain unclear. In this study, Landrace×Yorkshire crossbred sows were fed either standard (SP) or low-protein (LP, 50% of the SP) diets throughout gestation and lactation. Female offspring were fed the same diet after weaning until 6 months of age. LP offspring had higher serum 17β-estradiol level (P<0.01), which was accompanied by lower mRNA (P<0.05) but higher protein (P<0.05) expression of cytochrome P450 aromatase (CYP19A1) in the ovary. CYP19A1 protein up-regulation was associated with lower ovarian expression of drosha (P<0.05) and miRNAs targeting CYP19A1 (P<0.05). LP offspring had less graafian follicles with more apoptotic granulosa cells (P<0.05), as well as higher caspase 3 activity (P<0.05) and FasL expression (P<0.05) in the ovary. FasL gene up-regulation was associated with higher ERα protein expression (P<0.05) and binding to FasL gene promoter. These results suggest that a maternal LP diet in pregnancy and lactation elevated serum 17β-estradiol level by activating CYP19A1 through miRNA-mediated mechanism, and induced granulosa apoptosis in graafian follicles through ER-activated Fas/FasL-caspase 3 pathway.
Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China.
Shiyan
S
Sui
Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China.
Bin
B
He
Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China.
Yimin
Y
Jia
Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China.
Runsheng
R
Li
Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China.
Demin
D
Cai
Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China.
Xi
X
Li
Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China.
Haogang
H
Song
Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China.
Longfei
L
Jia
Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China. Electronic address: zhao.ruqian@gmail.com.
Ruqian
R
Zhao
D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006107:Granulosa Cells / Q000378:metabolism / Q000473:pathology; D007774:Lactation / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics; D006080:Ovarian Follicle / Q000378:metabolism* / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012741:Sexual Maturation / Q000502:physiology*; D013552:Swine; D014407:Tumor Cells, Cultured; D000098682:Steroidogenic Acute Regulatory Protein
D012739:Gonadal Steroid Hormones; D035683:MicroRNAs; D010750:Phosphoproteins; D012333:RNA, Messenger; D000098682:Steroidogenic Acute Regulatory Protein; D001141:Aromatase
Folliculogenesis; Maternal low-protein diet; Offspring; Ovary; Prepubertal gilts; Steroidogenesis