Mice lacking membrane estrogen receptor 1 are protected from reproductive pathologies resulting from developmental estrogen exposure†
| Autor: | Ellis R. Levin, Theresa I. Medrano, Jiude Mao, Paul S. Cooke, Cheryl S. Rosenfeld, Paul D. Caldo, Ana M Mesa, Madison T. Ortega, Manjunatha K. Nanjappa, Jessica A. Kinkade |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Membrane estrogen receptor steroid receptors Messenger Inbred Strains Diethylstilbestrol Uterus Estrogen receptor Reproductive health and childbirth Medical and Health Sciences Mice 0302 clinical medicine Pregnancy estrogen 2.1 Biological and endogenous factors Aetiology Pediatric Mice Knockout xenoestrogens General Medicine Biological Sciences Epididymis medicine.anatomical_structure vagina Genital Diseases Prenatal Exposure Delayed Effects 030220 oncology & carcinogenesis Ovariectomized rat Female Genital Diseases Male Non-Steroidal epididymis Research Article medicine.drug medicine.medical_specialty medicine.drug_class Knockout Mice Inbred Strains testis Biology 03 medical and health sciences Internal medicine medicine Animals Estrogens Non-Steroidal RNA Messenger Obstetrics & Reproductive Medicine uterus Contraception/Reproduction Estrogen Receptor alpha Estrogens Cell Biology 030104 developmental biology Endocrinology Gene Expression Regulation Reproductive Medicine Estrogen Infertility RNA Estrogen receptor alpha |
| Zdroj: | Biol Reprod Biology of reproduction, vol 101, iss 2 |
| ISSN: | 1529-7268 0006-3363 |
| Popis: | Both membrane and nuclear fractions of estrogen receptor 1 (ESR1) mediate 17β-estradiol (E2) actions. Mice expressing nuclear (n)ESR1 but lacking membrane (m)ESR1 (nuclear-only estrogen receptor 1 [NOER] mice) show reduced E2 responsivity and reproductive abnormalities culminating in adult male and female infertility. Using this model, we investigated whether reproductive pathologies caused by the synthetic estrogen diethylstilbestrol (DES) are mitigated by mESR1 ablation. Homozygous and heterozygous wild-type (WT and HET, respectively) and NOER male and female mice were subcutaneously injected with DES (1 mg/kg body weight [BW]) or vehicle daily from postnatal day (PND) 1–5. Uterine histology was assessed in select DES-treated females at PND 5, whereas others were ovariectomized at PND 60 and treated with E2 (10 μg/kg BW) or vehicle 2 weeks later. Neonatal DES exposure resulted in ovary-independent epithelial proliferation in the vagina and uterus of WT but not NOER females. Neonatal DES treatment also induced ovary-independent adult expression of classical E2-induced transcripts (e.g., lactoferrin [Ltf] and enhancer of zeste homolog 2 [Ezh2]) in WT but not NOER mice. At PND 90, DES-treated WT and HET males showed smaller testes and a high incidence of bacterial pyogranulomatous inflammation encompassing the testes, epididymis and occasionally the ductus deferens with spread to lumbar lymph nodes; such changes were largely absent in NOER males. Results indicate that male and female NOER mice are protected from deleterious effects of neonatal DES, and thus mESR1 signaling is required for adult manifestation of DES-induced reproductive pathologies in both sexes. |
| Databáze: | OpenAIRE |
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