<td>Under development: Not open for comment. Do not cite</td>
<td>Under Development: Contributions and Comments Welcome</td>
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<td>1.29</td>
<td>Under Development</td>
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<h2>Abstract</h2>
<p>During sexual differentiation and gonadal development in utero or in ovo, androgenic tissues develop, in part, under the control of testosterone (Viger et al. 2005). Reduction of circulating testosterone during this crucial time of development can result in malformed reproductive tracts in males. Exposure to drugs (e.g., statins) or other compounds may cause male reproductive tract abnormalities by inhibiting HMG-CoA reductase, which is the rate-limiting enzyme in the production of cholesteron, the precursor of testosterone.</p>
<h2>Abstract</h2>
<hr>
<p>During sexual differentiation and gonadal development in utero or in ovo, androgenic tissues develop, in part, under the control of testosterone (Viger et al. 2005). Reduction of circulating testosterone during this crucial time of development can result in malformed reproductive tracts in males. Exposure to drugs (e.g., statins) or other compounds may cause male reproductive tract abnormalities by inhibiting HMG-CoA reductase, which is the rate-limiting enzyme in the production of cholesteron, the precursor of testosterone.
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<h2>Overall Assessment of the AOP</h2>
<p>This AOP was developed primarily from one study of exposure of rats in utero to simvastatin (as well as a phthalate ester; Beverley et al., 2015) and biological plausibility. It currently should be considered putative and untested.
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<p>This AOP was developed primarily from one study of exposure of rats in utero to simvastatin (as well as a phthalate ester; Beverley et al., 2015) and biological plausibility. It currently should be considered putative and untested.</p>
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<h2>References</h2>
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<p>Beverly, B. E. J., et al. (2014). "Simvastatin and Dipentyl Phthalate Lower Ex Vivo Testicular Testosterone Production and Exhibit Additive Effects on Testicular Testosterone and Gene Expression Via Distinct Mechanistic Pathways in the Fetal Rat." Toxicological Sciences.
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<p>Beverly, B. E. J., et al. (2014). "Simvastatin and Dipentyl Phthalate Lower Ex Vivo Testicular Testosterone Production and Exhibit Additive Effects on Testicular Testosterone and Gene Expression Via Distinct Mechanistic Pathways in the Fetal Rat." Toxicological Sciences.</p>
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<h4>How it is Measured or Detected</h4>
<p>The activity of HMG-CoA reductase inhibition may be measured by a commercially available kit which measures a decrease in absorbance at 340 nm, which represents the oxidation of NADPH by the catalytic subunit of HMGR in the presence of the substrate HMG-CoA. Sterol Regulatory element-binding factor 1 (SREBF) is the transcription factor controlling downstream regulation of HMG-CoA reductase. The ToxCast assay ATG_SREBF1_CIS_up is one method of measuring transcriptional control of HMG-CoA reductase.
<h4>How it is Measured or Detected</h4>
<p>The activity of HMG-CoA reductase inhibition may be measured by a commercially available kit which measures a decrease in absorbance at 340 nm, which represents the oxidation of NADPH by the catalytic subunit of HMGR in the presence of the substrate HMG-CoA. Sterol Regulatory element-binding factor 1 (SREBF) is the transcription factor controlling downstream regulation of HMG-CoA reductase. The ToxCast assay ATG_SREBF1_CIS_up is one method of measuring transcriptional control of HMG-CoA reductase.
<p>Taxonomic Applicability: Cholesterol is synthesized in plants but acts as a precursor for different products than in animals (Sonawane et al. 2016). Within the animal kingdom most deuterostomes (including vertebrata, cyclostomata, cephalochordate, and echinodermata, but not chordata) possess the genes necessary for cholesterol biosynthesis. However, most protostomes (including arthropoda and nematomorpha) have lost these genes (Zhang et al., 2019). Thus far vertebrates are the primary consideration for this KE.</p>
<p>Lifestage Applicability: Cholesterol can be measured in organisms at all life stages. However, the size of young organisms may limit the ability to collect plasma for cholesterol analysis. Whole-body measurements or pooled samples may be more feasible.</p>
<p>Sex Applicability: Cholesterol measurements are applicable for all sexes</p>
<h4>Key Event Description</h4>
<p>Most cholesterol synthesis in vertebrates occurs within the endoplasmic reticulum of hepatic cells. First, acetyl-CoA is converted to HMG-CoA via HMG-CoA synthase. Next, HMG-CoA is converted to mevalonate via HMG-CoA reductase. Several other steps follow, but conversion of HMG-CoA to mevalonate is the rate-limiting step of cholesterol synthesis (Cerqueira et al. 2016; Risley 2002). Consequently, Statin drugs inhibit HMG-CoA reductase to reduce cholesterol (Pahan 2006).</p>
<p>Cholesterol synthesis may also occur to a limited extent in steroidogenic cells where it’s used to produce steroid hormones (Azhar et al., 2007)</p>
<p>Once cholesterol is produced in the liver, it’s transported in the plasma. Hydrophobic lipids like cholesterol, cholesteryl ester (a cholesterol molecule bound to a fatty acid), and triglycerides are transported via lipoprotein complexes. There are different groups of lipoproteins which use different proteins and ratios of lipids including high-density lipoprotein (HDL), low-density (LDL), and very low-density (VLDL).</p>
<p>Commerical assay kits are available for measuring cholesterol using either colorimetric or fluorometric detection. Total cholesterol assay kits often include cholesteryl esters in the measurement (<a href="https://www.cellbiolabs.com/total-cholesterol-assay-kit">Cell Bio Labs</a>, <a href="https://www.thermofisher.com/order/catalog/product/A12216#/A12216">ThermoFisher</a>). Additional kits are availalbe for measuring the cholesterol in the different lipoprotein complexes (<a href="https://www.cellbiolabs.com/hdl-and-ldlvldl-cholesterol-assay-kit">Cell Bio Labs</a>). </p>
<p>Oil Red O staining can be used for organisms such as zebrafish larvae that are clear, however it stains triglycerides and lipids not just cholesterol (Zhou et al., 2015). </p>
<p>Plasma cholesterol is a common clinical measurement in humans and the Abell-Kendall technique is the standard chemical determination method (Cox et al. 1990), although there are a wide variety of viable methods.</p>
<h4>References</h4>
<p>Al-Habsi, A.A., A. Massarsky, T.W. Moon (2016) “Exposure to gemfibrozil and atorvastatin affects cholesterol metabolism and steroid production in zebrafish (<em>Danio rerio</em>)”, <em>Comparative Biochemistry and Physiology, Part B, </em>Vol. 199, Elsevier, pp. 87-96. http://dx.doi.org/10.1016/j.cbpb.2015.11.009</p>
<p>Azhar, S., E. Reaven (2007) “Regulation of Leydig cell cholesterol metabolism”, in A.H. Payne, M.P. Hardy (eds.) <em>The Leydig Cell in Health and Disease, </em>Humana Press. https://doi.org/10.1007/978-1-59745-453-7</p>
<p>Cox RA, García-Palmieri MR. Cholesterol, Triglycerides, and Associated Lipoproteins. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 31. Available from: https://www.ncbi.nlm.nih.gov/books/NBK351/</p>
<p>Dai, W. et al. (2015) "High fat plus high cholesterol diet lead to hepatic steatosis in zebrafish larvae: a novel model for screening anti-hepatic steatosis drugs", <em>Nutrition and Metabolism</em>, Vol. 12(42), Springer Nature. DOI 10.1186/s12986-015-0036-z </p>
<p>Du, Z.Y. et al. (2008) “Hypolipidaemic effect of fenofibrate and fasting in the herbivorous grass carp (<em>Ctenopharyngodon idella) </em>fed a high-fat diet”, <em>British Journal of Nutrition, </em>Vol. 100, Cambridge University Press, pp. 1200-1212. doi:10.1017/S0007114508986840</p>
<p>Guo, X. et al. (2015) “Effects of lipid-lowering pharmaceutical clofibrate on lipid and lipoprotein metabolism of grass carp (<em>Ctenopharyngodon idellal </em>Val.) fed with the high non-protein energy diets”, <em>Fish Physiology and Biochemistry, </em>Vol. 41, Springer, pp. 331-343. doi: 10.1007/s10695-014-9986-8</p>
<p>Cerqueira, N. M., Oliveira, E. F., Gesto, D. S., Santos-Martins, D., Moreira, C., Moorthy, H. N., ... & Fernandes, P. A. (2016). Cholesterol biosynthesis: a mechanistic overview. <em>Biochemistry</em>, <em>55</em>(39), 5483-5506.</p>
<p>Prindiville, J.S. et al. (2011) “The fibrate drug gemfibrozil disrupts lipoprotein metabolism in rainbow trout”, <em>Toxicology and Applied Pharmacology, </em>Vol. 251, Elsevier, pp. 201-238. doi:10.1016/j.taap.2010.12.013</p>
<p>Pahan, K. (2006). Lipid-lowering drugs. <em>Cellular and molecular life sciences CMLS</em>, <em>63</em>(10), 1165-1178.</p>
<p>Risley, J. M. (2002). Cholesterol biosynthesis: Lanosterol to cholesterol. <em>Journal of chemical education</em>, <em>79</em>(3), 377.</p>
<p>Velasco-Santamaría, Y.M. et al. (2011) “Bezafibrate, a lipid-lowering pharmaceutical, as a potential endocrine disruptor in male zebrafish (<em>Danio rerio</em>)”, <em>Aquatic Toxicology, </em>Vol. 105, Elsevier, pp. 107-118. doi:10.1016/j.aquatox.2011.05.018</p>
<p>Zhang, T. et al. (2019) “Evolution of the cholesterol biosynthesis pathway in animals”, <em>Molecular Biology and Evolution, </em>Vol. 36(11), Oxford University Press, pp. 2548-2556. doi:10.1093/molbev/msz167</p>
<p>Zhou, J. et al. (2015) "Rapid analysis of hypolipidemic drugs in a live zebrafish assay", <em>Journal of Pharmacological and Toxicological Methods, </em>Vol. 72, Elsevier, pp. 47-52. http://dx.doi.org/10.1016/j.vascn.2014.12.002</p>
<td><a href="/aops/307">Aop:307 - Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring</a></td>
<td>KeyEvent</td>
</tr>
<tr>
<td><a href="/aops/526">Aop:526 - Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis</a></td>
<td>KeyEvent</td>
</tr>
<tr>
<td><a href="/aops/124">Aop:124 - HMG-CoA reductase inhibition leading to decreased fertility</a></td>
<td>KeyEvent</td>
</tr>
<tr>
<td><a href="/aops/18">Aop:18 - PPARα activation in utero leading to impaired fertility in males</a></td>
<td>KeyEvent</td>
</tr>
<tr>
<td><a href="/aops/51">Aop:51 - PPARα activation leading to impaired fertility in adult male rodents </a></td>
<td>KeyEvent</td>
</tr>
<tr>
<td><a href="/aops/496">Aop:496 - Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）</a></td>
<td>KeyEvent</td>
</tr>
<tr>
<td><a href="/aops/64">Aop:64 - Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility</a></td>
<td>KeyEvent</td>
</tr>
<tr>
<td><a href="/aops/120">Aop:120 - Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)</a></td>
<td>KeyEvent</td>
</tr>
<tr>
<td><a href="/aops/288">Aop:288 - Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)</a></td>
<td>KeyEvent</td>
</tr>
<tr>
<td><a href="/aops/570">Aop:570 - Decreased testosterone synthesis leading to hypospadias in male (mammalian) offspring</a></td>
<td>KeyEvent</td>
</tr>
<tr>
<td><a href="/aops/575">Aop:575 - Decreased testosterone synthesis leading to increased nipple retention (NR) in male (rodent) offspring</a></td>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif">This key event (KE) is applicable to all mammals, as the synthesis and role of testosterone are evolutionarily conserved (Vitousek et al., 2018). Both sexes produce and require testosterone, which plays critical roles throughout life, from development to adulthood; albeit there are differences in lief stages when testosterone exert specific effects and function (Luetjens & Weinbauer, 2012; Naamneh Elzenaty et al., 2022). Accordingly, this KE applies to both males and females across all life stages, but life stage should be considered when embedding in AOPs. </span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif">Notably, the key enzymes involved in testosterone production first appeared in the common ancestor of amphioxus and vertebrates (Baker, 2011). This suggests that the KE has a broader domain of applicability, encompassing non-mammalian vertebrates. AOP developers are encouraged to integrate additional knowledge to expand its relevance beyond mammals to other vertebrates.</span></span></p>
<h4>Key Event Description</h4>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><span style="background-color:white"><span style="color:black">Testosterone is an endogenous steroid hormone that acts by binding the androgen receptor (AR) in androgen-responsive tissues (Murashima et al., 2015). As with all steroid hormones, testosterone is produced through steroidogenesis, an enzymatic pathway converting cholesterol into all the downstream steroid hormones. Briefly, androstenedione or androstenediol is converted to testosterone by the enzymes 17β-hydroxysteroid dehydrogenase (HSD) or 3β-HSD, respectively. Testosterone can then be converted to the more potent androgen, dihydrotestosterone (DHT) by 5α-reductase, or aromatized by CYP19A1 (Aromatase) into estrogens. Testosterone secreted in blood circulation can be found free or bound to SHBG or albumin (Trost & Mulhall, 2016). </span></span></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><span style="background-color:white"><span style="color:black">Testosterone is produced mainly by the testes (in males), ovaries (in females) and to a lesser degree in the adrenal glands. The output of testosterone from different tissues varies with life stages. During fetal development testosterone is crucial for the differentiation of male reproductive tissues and the overall male phenotype. In adulthood, testosterone synthesis is controlled by the Hypothalamus-Pituitary-Gonadal (HPG) axis. GnRH is released from the hypothalamus inducing LH pulses secreted by the anterior pituitary. This LH surge leads to increased testosterone production, both in testes (males) and ovaries (females). If testosterone reaches low levels, this axis is once again stimulated to increase testosterone synthesis. This feedback loop is essential for maintenance of appropriate testosterone levels (Chandrashekar & Bartke, 1998; Ellis et al., 1983; Rey, 2021).</span></span></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><span style="background-color:white"><span style="color:black">By disrupting e.g. steroidogenesis or the HPG-axis, testosterone synthesis or homeostasis may be disrupted and can lead to less testosterone being synthesized and released into circulation. </span></span></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><u><span style="background-color:white"><span style="color:black">General role in biology</span></span></u></span></span></p>
<p style="text-align:justify"><span style="font-size:11.0pt"><span style="background-color:white"><span style="font-family:"Calibri",sans-serif"><span style="color:black">Androgens are essential hormones responsible for the development of the male phenotype during fetal life and for sexual maturation at puberty. In adulthood, androgens remain essential for the maintenance of male reproductive function and behavior but is also essential for female fertility. Apart from their effects on reproduction, androgens affect a wide variety of non-reproductive tissues such as skin, bone, muscle, and brain (Heemers et al 2006). Androgens, principally testosterone and DHT, exert most of their effects by interacting with the AR (Murashima et al 2015). </span></span></span></span></p>
<h4>How it is Measured or Detected</h4>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><span style="font-size:10.5pt"><span style="background-color:white"><span style="color:black">Testosterone levels can be quantified in serum (in vivo), cell culture medium (in vitro), or tissue (ex vivo, in vitro). Methods include traditional immunoassays such as ELISA and RIA, advanced techniques like LC-MS/MS, and liquid scintillation spectrometry following radiolabeling (Shiraishi et al., 2008).</span></span></span></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><span style="font-size:10.5pt"><span style="background-color:white"><span style="color:black">The H295R Steroidogenesis Assay (OECD TG 456) is (currently; anno 2025) primarily used to measure estradiol and testosterone production. This validated OECD test guideline uses adrenal H295R cells, with hormone levels measured in the cell culture medium (OECD, 2011). H295R adrenocortical carcinoma cells express the key enzymes and hormones of the steroidogenic pathway, enabling broad analysis of steroidogenesis disruption by quantifying hormones in the medium using LC-MS/MS. Initially designed to assess testosterone and estradiol levels, the assay now extends to additional steroid hormones, such as progesterone and pregnenolone. The U.S. EPA’s ToxCast program further advanced this method, enabling high-throughput measurement of 11 steroidogenesis-related hormones (Haggard et al., 2018). While the H295R assay indirectly reflects disruptions in overall steroidogenesis (e.g., changes in testosterone levels), it does not provide mechanistic insights.</span></span></span></span></span></p>
<p><span style="font-size:10.5pt"><span style="background-color:white"><span style="font-family:"Calibri",sans-serif"><span style="color:black">Testosterone can be measured by immunoassays and by isotope-dilution gas chromatography-mass spectrometry in serum (Taieb et al., 2003; Paduch et al., 2014). Testosterone levels may also be measured by: Fish Lifecycle Toxicity Test (FLCTT) (US EPA OPPTS 850.1500), Male pubertal assay (PP Male Assay) (US EPA OPPTS 890.1500), OECD TG 441: Hershberger Bioassay in Rats (H Assay).</span></span></span></span></p>
<h4>References</h4>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif">Baker, M.E. (2011). Insights from the structure of estrogen receptor into the evolution of estrogens: implications for endocrine disruption. Biochem Pharmacol, 82(1), 1-8. <a href="https://doi.org/10.1016/j.bcp.2011.03.008" style="color:blue; text-decoration:underline">https://doi.org/10.1016/j.bcp.2011.03.008</a> </span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif">Chandrashekar, V., & Bartke, A. (1998). The Role of Growth Hormone in the Control of Gonadotropin Secretion in Adult Male Rats*. Endocrinology, 139(3), 1067–1074. <a href="https://doi.org/10.1210/endo.139.3.5816" style="color:blue; text-decoration:underline">https://doi.org/10.1210/endo.139.3.5816</a> </span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif">Ellis, G. B., Desjardins, C., & Fraser, H. M. (1983). Control of Pulsatile LH Release in Male Rats. Neuroendocrinology, 37(3), 177–183. <a href="https://doi.org/10.1159/000123540" style="color:blue; text-decoration:underline">https://doi.org/10.1159/000123540</a> </span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif">Haggard, D. E., Karmaus, A. L., Martin, M. T., Judson, R. S., Setzer, R. W., & Paul Friedman, K. (2018). High-Throughput H295R Steroidogenesis Assay: Utility as an Alternative and a Statistical Approach to Characterize Effects on Steroidogenesis. Toxicological Sciences, 162(2), 509–534. <a href="https://doi.org/10.1093/toxsci/kfx274" style="color:blue; text-decoration:underline">https://doi.org/10.1093/toxsci/kfx274</a> </span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif">Heemers, H. V, Verhoeven, G., & Swinnen, J. V. (2006). Androgen activation of the sterol regulatory element-binding protein pathway: Current insights. Molecular Endocrinology (Baltimore, Md.), 20(10), 2265–77. doi:10.1210/me.2005-0479 </span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif">Luetjens, C. M., & Weinbauer, G. F. (2012). Testosterone: biosynthesis, transport, metabolism and (non-genomic) actions. In Testosterone (pp. 15–32). Cambridge University Press. <a href="https://doi.org/10.1017/CBO9781139003353.003" style="color:blue; text-decoration:underline">https://doi.org/10.1017/CBO9781139003353.003</a> </span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif">Murashima, A., Kishigami, S., Thomson, A., & Yamada, G. (2015). Androgens and mammalian male reproductive tract development. Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 1849(2), 163–170. <a href="https://doi.org/10.1016/j.bbagrm.2014.05.020" style="color:blue; text-decoration:underline">https://doi.org/10.1016/j.bbagrm.2014.05.020</a> </span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif">Naamneh Elzenaty, R., du Toit, T., & Flück, C. E. (2022). Basics of androgen synthesis and action. Best Practice & Research Clinical Endocrinology & Metabolism, 36(4), 101665. <a href="https://doi.org/10.1016/j.beem.2022.101665" style="color:blue; text-decoration:underline">https://doi.org/10.1016/j.beem.2022.101665</a> </span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif">Paduch, D. A., Brannigan, R. E., Fuchs, E. F., Kim, E. D., Marmar, J. L., & Sandlow, J. I. (2014). The laboratory diagnosis of testosterone deficiency. Urology, 83(5), 980–8. <a href="https://doi.org/10.1016/j.urology.2013.12.024" style="color:blue; text-decoration:underline">https://doi.org/10.1016/j.urology.2013.12.024</a> </span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif">Rey, R. A. (2021). The Role of Androgen Signaling in Male Sexual Development at Puberty. Endocrinology, 162(2). <a href="https://doi.org/10.1210/endocr/bqaa215" style="color:blue; text-decoration:underline">https://doi.org/10.1210/endocr/bqaa215</a> </span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif">Shiraishi, S., Lee, P. W. N., Leung, A., Goh, V. H. H., Swerdloff, R. S., & Wang, C. (2008). Simultaneous Measurement of Serum Testosterone and Dihydrotestosterone by Liquid Chromatography–Tandem Mass Spectrometry. Clinical Chemistry, 54(11), 1855–1863. <a href="https://doi.org/10.1373/clinchem.2008.103846" style="color:blue; text-decoration:underline">https://doi.org/10.1373/clinchem.2008.103846</a> </span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif">Taieb, J., Mathian, B., Millot, F., Patricot, M.-C., Mathieu, E., Queyrel, N., … Boudou, P. (2003). Testosterone measured by 10 immunoassays and by isotope-dilution gas chromatography-mass spectrometry in sera from 116 men, women, and children. Clinical Chemistry, 49(8), 1381–95.</span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif">Trost, L. W., & Mulhall, J. P. (2016). Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials. The Journal of Sexual Medicine, 13(7), 1029–1046. <a href="https://doi.org/10.1016/j.jsxm.2016.04.068" style="color:blue; text-decoration:underline">https://doi.org/10.1016/j.jsxm.2016.04.068</a> </span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif">Vitousek, M. N., Johnson, M. A., Donald, J. W., Francis, C. D., Fuxjager, M. J., Goymann, W., Hau, M., Husak, J. F., Kircher, B. K., Knapp, R., Martin, L. B., Miller, E. T., Schoenle, L. A., Uehling, J. J., & Williams, T. D. (2018). HormoneBase, a population-level database of steroid hormone levels across vertebrates. Scientific Data, 5(1), 180097. <a href="https://doi.org/10.1038/sdata.2018.97" style="color:blue; text-decoration:underline">https://doi.org/10.1038/sdata.2018.97</a> </span></span></p>
<h4><a href="/events/809">Event: 809: malformed, Male reproductive tract</a></h4>
<h5>Short Name: malformed, Male reproductive tract</h5>