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AOP: 445
Title
Estrogen Receptor Alpha Agonism leads to Impaired Reproduction
Short name
Graphical Representation
Point of Contact
Contributors
- John Hoang
Coaches
OECD Information Table
OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
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This AOP was last modified on April 29, 2023 16:03
Revision dates for related pages
Page | Revision Date/Time |
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Increased, Kisspeptin signalling | April 05, 2022 00:47 |
Decreased, Gonadotropins | April 05, 2022 00:49 |
Decreased, Androgen and Progestin | June 06, 2022 13:38 |
Decreased, Maturation Inducing Steroid Surge by Granulosa cells | April 05, 2022 00:54 |
Impaired, Oocyte maturation and ovulation | April 05, 2022 00:54 |
Increased, Oocyte Atresia | April 05, 2022 00:55 |
Impaired, Reproduction | April 05, 2022 00:57 |
Activation, estrogen receptor alpha | August 14, 2024 16:29 |
Activation, estrogen receptor alpha leads to Increased, Kisspeptin signalling | August 15, 2022 02:42 |
Increased, Kisspeptin signalling leads to Decreased, Gonadotropins | August 15, 2022 02:43 |
Activation, estrogen receptor alpha leads to Decreased, Gonadotropins | August 15, 2022 02:43 |
Decreased, Gonadotropins leads to Decreased , Androgen and Progestin | April 05, 2022 00:58 |
Activation, estrogen receptor alpha leads to Impaired, Reproduction | August 15, 2022 02:46 |
Decreased , Androgen and Progestin leads to Decreased, Maturation Inducing Steroids Surge by Granulosa cells | April 05, 2022 00:58 |
Decreased, Maturation Inducing Steroids Surge by Granulosa cells leads to Impaired, Oocyte maturation and ovulation | April 05, 2022 00:59 |
Impaired, Oocyte maturation and ovulation leads to Increased, Oocyte Atresia | April 05, 2022 00:59 |
Increased, Oocyte Atresia leads to Impaired, Reproduction | April 05, 2022 00:59 |
Abstract
Estrogen Receptor Alpha(ERalpha) is a nuclear transcription factor that is activated by estrogens, a group of hormones involved in reproductive development. ERalpha is involved in the transcription and regulation of physiological processes involved in the endocrine system. Birth control pills contain estrogens which often end up in wastewater streams and allow for exogenous exposures to many fish. This AOP connects ERalpha agonism to decreased, cumulative fecundity as a result of impairment within the endocrine system. In particular, the activation of ERalpha in kisspeptin cells located within the hypothalamus causes increased kisspeptin signaling. This increased signaling causes an increase in gonadotropin-releasing hormone(GnRH). The increase of GnRH causes increased negative feedback response on the release of gonadotropins, resulting in a decrease in gonadotropin levels. The decreased gonadotropin levels lead to a decrease in androgen and progestin production by theca cells within the ovary. The decrease in androgen and progestin levels causes a decrease in maturation-inducing steroids by the granulosa cells within the ovary. A reduction in maturation-inducing steroids causes impairment in oocyte maturation and ovulation thereby resulting in an increase in oocyte atresia and a decrease in cumulative fecundity.
AOP Development Strategy
Context
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
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MIE | 1065 | Activation, estrogen receptor alpha | Activation, estrogen receptor alpha |
KE | 1985 | Increased, Kisspeptin signalling | Increased, Kisspeptin signalling |
KE | 1986 | Decreased, Gonadotropins | Decreased, Gonadotropins |
KE | 1987 | Decreased, Androgen and Progestin | Decreased , Androgen and Progestin |
KE | 1988 | Decreased, Maturation Inducing Steroid Surge by Granulosa cells | Decreased, Maturation Inducing Steroids Surge by Granulosa cells |
KE | 1989 | Impaired, Oocyte maturation and ovulation | Impaired, Oocyte maturation and ovulation |
KE | 1990 | Increased, Oocyte Atresia | Increased, Oocyte Atresia |
AO | 1991 | Impaired, Reproduction | Impaired, Reproduction |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
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Activation, estrogen receptor alpha leads to Decreased, Gonadotropins | non-adjacent | Moderate | Moderate |
Activation, estrogen receptor alpha leads to Impaired, Reproduction | non-adjacent | High | Moderate |