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Relationship: 2274
Title
Impaired, Spermatogenesis leads to impaired, Fertility
Upstream event
Downstream event
Key Event Relationship Overview
AOPs Referencing Relationship
AOP Name | Adjacency | Weight of Evidence | Quantitative Understanding | Point of Contact | Author Status | OECD Status |
---|---|---|---|---|---|---|
PPARalpha Agonism Impairs Fish Reproduction | adjacent | High | Not Specified | Ashley Kittelson (send email) | Under development: Not open for comment. Do not cite |
Taxonomic Applicability
Sex Applicability
Sex | Evidence |
---|---|
Male | High |
Life Stage Applicability
Term | Evidence |
---|---|
Adult, reproductively mature | High |
Key Event Relationship Description
Spermatogenesis is a multiphase process of cellular transformation that produces mature male gametes known as sperm for sexual reproduction (Kang et al., 2015). The process of spermatogenesis can be broken down into 3 phases: the mitotic proliferation of spermatogonia, meiosis, and post meiotic differentiation(spermiogenesis) (Boulanger et al., 2015). Male fertility is dependent on the quantity as well as the proper cellular morphology of the sperm formed in the testes (Chen et al., 2020). The fusion of sperm and oocytes is the key step for the beginning of life known as fertilization (Alavi et al., 2019). Impaired spermatogenesis may impact fertility and, consequently, also reduce reproduction.
Evidence Supporting this KER
Evidence supporting the KER is shown below.
Biological Plausibility
Spermatogenesis is one of the most conserved biological processes from Drosophila to humans (Wu et al., 2016). The process itself is well understood and gametes produced from spermatogenesis are required for sexual reproduction.
Empirical Evidence
- Dose concordance
- When exposed to 50 mg DEHP kg-1 via intraperitoneal injection for 10 days, zebrafish (Danio rerio) experienced a reduction in the proportion of spermatozoa present compared to the control group. However, the zebrafish did not experience a significant decrease in fertilization success. Whereas when exposed to 5000 mg of DEHP kg-1 the same method, it experienced both a reduction in spermatozoa and fertilization success (Uren-Webster et al., 2010).
- Spermatozoa from mice (Mus musculus) exposed to 0.0001, 0.01, and 1 µM for 6 hours did not experience any significant changes in sperm motility parameters, fertilization rate, and developmental success. However, when exposed to 100 µM for 6 hours, spermatozoa experienced significant decreases in sperm motility parameters, fertilization rate, and developmental success (Rahman et al., 2014).
- Temporal concordance
- At 40-, 45-, and 65-days post fertilization(dpf), Fshr and lhcgr double mutant zebrafish (Danio rerio) encountered arrest of spermatogonial stage with apoptotic oocyte-like germ cells and at 90 dpf, the double knockouts were completely infertile (Zhang et al., 2015).
- At 65 dpf, zebrafish (Danio rerio) exposed to 10 uM of BPA experienced significantly reduced size of testis and delayed spermatogenesis. At 120 dpf, the same zebrafish were completely infertile and unable to induce egg laying by females (Song et al., 2020).
Uncertainties and Inconsistencies
- When exposed to 10 and 100 ng/L of EE2 for 62 days leading to spawning, Rainbow trout (Oncorhynchus mykiss) experienced a decrease in GSI and increases in sperm concentration and spermatocrit. However, there were no significant changes to spermatogenesis. Despite this, there was a decrease in viability of embryos. (Schultz et al., 2003)
- Male Sprague-Dawley rats (Rattus norvegicus) fed a high fat diet(allowing them to develop Non-alcoholic fatty liver disease) experienced decreased testosterone levels along with reduced sperm number and motility. However, this did not affect fertility of the rats (Li et al., 2013).
Quantitative Understanding of the Linkage
Quantitative understanding is shown bellow.
Response-response Relationship
- Lahnsteiner et al.(1998) determined that fertilization rate in Rainbow Trout (Oncorhynchus mykiss) can be described by sperm motility rate(y=0.72x * 25.99 where y is fertilization rate and x is sperm motility rate, R=0.594, P < 0.001), seminal plasma pH(R2=0.525, P < 0.001), and spermatozoal respiration activation(R2=0.554, P < 0.001). They found a positive correlation between % of motile spermatozoa and total swimming velocity with fertilization rate (P < 0.001) and % of immotile spermatozoa inversely. The 2 parameters accounted for 65% of total variance in fertilization rate.
- Relative sperm velocity(p=0.008) and longevity (p < 0.0001) showed significant association with sperm competition success in Atlantic salmon (Salmo salar). Males with faster spermatozoa achieved greater fertilization success. (Gage et al., 2004)
- Highly significant correlations were found between sperm motility (R=0.932, p < 0.001) and fertilization rate in Rainbow Trout (Oncorhynchus mykiss) (Ciereszko and Dabrowski, 1993).
Time-scale
- The duration of spermatogenesis in humans (Homo sapiens) is reported to be 74 days (Griswold, M.D, 2016). Consequently, effects on spermatogenesis may not manifest as observable impacts on fertility until perhaps 74 days after impacts on spermatogenesis began. This may vary depending on the stage(s) of spermatogenesis that are impacted by the stressor.
- The duration of the meiotic and spermiogenic phases in zebrafish (Danio rerio) is reported to be 6 days which means there could be a delay of at least 6 days before signs of impaired fertility may be detected (Leal et al., 2009).
Known modulating factors
- Fertilization success in Chinook salmon (Oncorhynchus tshawytscha) was significantly biased towards the male whose sperm swam fastest in the female’s ovarian fluid (Rosengrave et al., 2016).
- Seminal plasma pH(R2=0.525) is positively correlated with fertilization rate in Rainbow Trout (Oncorhynchus mykiss) and African catfish (Clarias gariepinus) (Lahnsteiner et al., 1998, Mansour et al., 2005).
Known Feedforward/Feedback loops influencing this KER
Feedforward/feedback loops haven’t been evaluated yet. However, given that fertilization pertains to the interaction between sperm and oocyte, it seems unlikely that fertilization rates (external to the male) would feedback on and impact spermatogenesis.
Domain of Applicability
- Taxonomic Applicability: Spermatogenesis is one of the most conserved biological processes from Drosophila to humans (Wu et al., 2016). As a result, animals who utilize sexual reproduction as their way to produce offspring are heavily reliant on spermatogenesis being effective and normal (Kang et al., 2015). There are studies on reproduction and spermatogenesis across a multitude of taxas.
- Sex Applicability: Spermatogenesis is a male-specific process (Tang et al., 2018, Wu et al., 2015, Kang et al., 2015, Wang et al., 2015). Thus, the present relationship is only relevant for males.
- Life Stage Applicability: Spermatogenesis and reproduction are only relevant for sexually-mature adults.
References
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