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Relationship: 2481
Title
Oocyte meiosis, disrupted leads to Ovarian follicle pool, reduced
Upstream event
Downstream event
AOPs Referencing Relationship
| AOP Name | Adjacency | Weight of Evidence | Quantitative Understanding | Point of Contact | Author Status | OECD Status |
|---|---|---|---|---|---|---|
| Inhibition of ALDH1A (RALDH) leading to impaired fertility via disrupted meiotic initiation of fetal oogonia of the ovary | adjacent | Moderate | Moderate | Cataia Ives (send email) | Under development: Not open for comment. Do not cite | Under Development |
Taxonomic Applicability
Sex Applicability
| Sex | Evidence |
|---|---|
| Female | High |
Life Stage Applicability
| Term | Evidence |
|---|---|
| Foetal | High |
The establishment of the primordial follicle pool is a multistep process that spans from early fetal life to reproductive maturity. This period of time varies greatly between species, lasting only a few weeks in mice and rats, but years in humans (Tingen et al, 2009). One important process is for the mitotic primordial germs cells to enter meiosis prior to cyst formation (Findlay et al, 2015; Tingen et al, 2009). Notably, in females there is a massive loss of oocytes between cyst formation and time of maturity, and the exact mechanisms behind this oocyte degradation is not well understood (Findlay et al, 2015; Sun et al, 2017).
| ID | Experimental Design | Species | Upstream Observation | Downstream Observation | Citation (first author, year) | Notes |
|---|
| Title | First Author | Biological Plausibility |
Dose Concordance |
Temporal Concordance |
Incidence Concordance |
|---|
Biological Plausibility
Dose Concordance Evidence
Temporal Concordance Evidence
Incidence Concordance Evidence
Uncertainties and Inconsistencies
atRA is synthesized from vitamin A in a two-step enzymatic pathway. Vitamin A is required from the diet; hence, dietary changes to vitamin A can greatly affect the level of available atRA and thus modulate atRA-regulated responses.
The quantitative understanding of this KER remains poorly understood, not least because the quantification of actual oocyte numbers at various stages of development are very difficult perform.
Response-response Relationship
The ovarian follicle pool (ovarian reserve) refers to the final number of primordial follicles in the mature ovary and is established through a series of events. In most mammals, it is determined during gestation or just after birth and relies on i) how many germ cells were established during embryogenesis, ii) their proliferation during migration and early ovary development, iii) death rate during oogenesis and iv) formation of primordial follicles at nest breakdown (Findlay et al, 2015). The last two stages, which includes nest formation and breakdown, is largely influenced by the mitotic-meiotic transition, in that oocytes that have failed to enter meiosis may contribute to the cysts population, but only high quality oocytes in meiotic prophase are spared during cyst breakdown (Findlay et al, 2015). Thus, there is a response-response relationship between meiotic entry and final follicle pool, albeit the quantitative relationship is not that well understood.
Time-scale
The time-scale for oocyte mitotic-meiotic transition and subsequent nest breakdown varies between species, but generally takes place from mid gestation to around the time of birth. In mice, meiosis and nest formation is initiated from around E13, whereas in humans it initiates at around GW12-14 (Childs et al, 2012; Findlay et al, 2015; Grive & Freiman, 2015; Pepling, 2006; Tingen et al, 2009). Nest breakdown starts just before birth in mice and completes around postnatal day 5 (Grive & Freiman, 2015; Pepling, 2006). In humans, nest breakdown takes place during second trimester (Grive & Freiman, 2015; Tingen et al, 2009).