Developmental programming: Impact of fetal exposure to endocrine-disrupting chemicals on gonadotropin-releasing hormone and estrogen receptor mRNA in sheep hypothalamus

Journal Article · Wed Sep 01 04:00:00 EDT 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.05.017· OSTI ID:21460202

Mahoney, Megan M ^[1]; Padmanabhan, Vasantha ^[2]

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1. Veterinary Biosciences and Neuroscience Program, University of Illinois, 2001 S. Lincoln Ave., Urbana IL. 61802 (United States)
2. Department of Pediatrics and Reproductive Sciences Q1 Program, University of Michigan, 300 N. Ingalls Bldg., Rm. 1109 SW, Ann Arbor, MI 48109-0404 (United States)

Bisphenol-A (BPA) and methoxychlor (MXC), two endocrine-disrupting chemicals (EDCs) with estrogenic and antiandrogenic effects, disrupt the reproductive system. BPA has profound effects on luteinizing hormone (LH) surge amplitude, and MXC has profound effects on on LH surge timing in sheep. The neural mechanisms involved in the differential disruption of the LH surge by these two EDCs remain to be elucidated. We tested the hypothesis that the differential effects of BPA and MXC on LH surge system involved changes in hypothalamic gonadotropin-releasing hormone (GnRH) and estrogen receptors (ESR), ESR1 and ESR2, mRNA expression. Pregnant sheep were given daily injections of cottonseed oil (controls), MXC, or BPA (5 mg/kg/day) from day 30 to 90 of gestation (term 147 d). Offspring from these animals were euthanized as adults, during the late follicular phase following synchronization of estrus with prostaglandin F{sub 2{alpha}}, just before the expected onset of preovulatory LH surge and changes in mRNA expression of hypothalamic GnRH, ESR1, and ESR2 quantified following in situ hybridization. GnRH mRNA expression was significantly lower in both groups of EDC-treated females compared to controls. ESR1 expression was increased in prenatal BPA- but not MXC-treated females in medial preoptic area relative to controls. In contrast, ESR2 expression was reduced in the medial preoptic area of both EDC-treated groups. Differences in expression of ESR1/ESR2 receptors may contribute to the differential effects of BPA and MXC on the LH surge system. These findings provide support that prenatal exposure to EDCs alters the neural developmental trajectory leading to long-term reproductive consequences in the adult female.

• OSTI ID: 21460202
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 247; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMALS
BODY
BRAIN
CARBOHYDRATES
CENTRAL NERVOUS SYSTEM
DOMESTIC ANIMALS
ESTROGENS
GLYCOPROTEINS
GONADOTROPINS
HORMONES
HYPOTHALAMUS
LIBERINS
LUTEINIZING HORMONE
MAMMALS
MEMBRANE PROTEINS
MESSENGER-RNA
NERVOUS SYSTEM
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PITUITARY HORMONES
PROTEINS
RECEPTORS
REPRODUCTION
RNA
RUMINANTS
SACCHARIDES
SHEEP
STEROID HORMONES
VERTEBRATES