The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism
Open accessAbstract
Becoming a phenotypic male is ultimately determined by androgen-induced masculinization. Disorders of fetal masculinization, resulting in hypospadias or cryptorchidism, are common, but their cause remains unclear. Together with the adult-onset disorders low sperm count and testicular cancer, they can constitute a testicular dysgenesis syndrome (TDS). Although masculinization is well studied, no unifying concept explains normal male reproductive development and its abnormalities, including TDS. We exposed rat fetuses to either anti-androgens or androgens and showed that masculinization of all reproductive tract tissues was programmed by androgen action during a common fetal programming window. This preceded morphological differentiation, when androgen action was, surprisingly, unnecessary. Only within the programming window did blocking androgen action induce hypospadias and cryptorchidism and altered penile length in male rats, all of which correlated with anogenital distance (AGD). Androgen-driven masculinization of females was also confined to the same programming window. This work has identified in rats a common programming window in which androgen action is essential for normal reproductive tract masculinization and has highlighted that measuring AGD in neonatal humans could provide a noninvasive method to predict neonatal and adult reproductive disorders. Based on the timings in rats, we believe the programming window in humans is likely to be 8-14 weeks of gestation.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Originating from the embryonic yolk sac, microglia migrate and colonize the brain during early development, around embryonic day (E)9.5 in mice.”
From Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus (2025) · cites this paper as [31]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“This precedes a hormonal surge in the brain, with androgens and estrogens peaking at around E17.5–18 [29–34].”
From Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus (2025) · cites this paper as [31]
Experimental — accuracy not yet measuredIn the citing paper
“Normal masculinization of the fetus is dependent upon androgen secretion by the testis, and androgens act initially during a critical masculinization programming window to ensure normal male reproductive development [3–5].”
From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [5]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The Physiology of Reproduction
Legendre, M., & Jalabert, B. (1988) · Annals of Internal Medicine · doi:10.7326/0003-4819-109-2-176_1 · Cited by 7,876
Skakkebæk, N. E., Meyts, E. R., & Main, K. M. (2001) · Human Reproduction · doi:10.1093/humrep/16.5.972 · Cited by 2,261
Male development of chromosomally female mice transgenic for Sry
Koopman, P. A., Gubbay, J., Vivian, N., Goodfellow, P. N., & Lovell-Badge, R. H. (1991) · Nature · doi:10.1038/351117a0 · Cited by 2,193
Decrease in anogenital distance among male infants with prenatal phthalate exposure
Swan, S. H., Main, K. M., Liu, F., Stewart, S. L., Kruse, R. L., Calafat, A. M., Mao, C. S., Redmon, J. B., Ternand, C. L., Sullivan, S., et al. (2005) · Environmental Health Perspectives · doi:10.1289/ehp.8100 · Cited by 1,586
Brodie, S. E. (1996) · Survey of Ophthalmology · doi:10.1016/s0039-6257(96)80075-0 · Cited by 770
Testosterone Formation and Metabolism During Male Sexual Differentiation in the Human Embryo
Siiteri, P. K., & Wilson, J. D. (1974) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-38-1-113 · Cited by 591
Studies on Sex Differentiation in Mammals
JOST, A., Vigier, B., Prépin, J., & PERCHELLET, J. P. (1973) · Elsevier eBooks · doi:10.1016/b978-0-12-571129-6.50004-x · Cited by 566
Fisher, J. S. (2003) · Human Reproduction · doi:10.1093/humrep/deg273 · Cited by 550
Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries
Boisen, K. A., Kaleva, M. M., Main, K. M., Virtanen, H. E., Haavisto, A.-M., Schmidt, I., Chellakooty, M., Damgaard, I., Kai, C. M., Reunanen, M. S., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)15998-9 · Cited by 510
Testicular dysgenesis syndrome: mechanistic insights and potential new downstream effects
Sharpe, R. M., & Skakkebæk, N. E. (2008) · Fertility and Sterility · doi:10.1016/j.fertnstert.2007.12.026 · Cited by 452
Research works printed but not linked: 10
- Jost, 1972, Johns Hopkins Med. J., 130, 38
- Sharpe, 2008, Fertil. Steril.
- Inomata, 1985, Jikken Dobutsu., 34, 439
- Jirasek, 1977, Birth Defects Orig. Artic. Ser., 13, 13
- Wyndham, 1943, J. Anat., 77, 179
- 10.1210/en.131.3.1149 · DOI
- Jost, 1973, Recent Prog. Horm. Res., 29, 1
- Stinnakre, 1975, Arch. Anat. Microsc. Morphol. Exp., 64, 45
- Murakami, 1987, J. Anat., 153, 223
- Hsieh, 2008, Curr. Urol. Rep.
Cited by
Sorted by citations
Items 401–500 of 782
Hyuga, T., Alcantara, M. C., Kajioka, D., Haraguchi, R., Suzuki, K., Miyagawa, S., Kojima, Y., Hayashi, Y., & Yamada, G. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms21010058 · Cited by 16
Grouping of phthalates for risk characterization of human exposures
Dekant, W. (2020) · Toxicology Letters · doi:10.1016/j.toxlet.2020.05.003 · Cited by 16
Rodriguez, K. F., Mellouk, N., Ungewitter, E. K., Nicol, B., Liu, C., Brown, P. R., Willson, C. J., & Yao, H. H. (2020) · Reproductive Toxicology · doi:10.1016/j.reprotox.2020.05.006 · Cited by 16
“Anogenital distance is an indicator of male reproductive health and a reduction of its length increased the risk of hypospadias and cryptorchidism in human and rodents [30, 31].”
Prenatal Exposure to Cigarette Smoke and Anogenital Distance at 4 Years in the INMA-Asturias Cohort
García‐Villarino, M., Fernández‐Iglesias, R., Galán, I. R., Rodríguez-Dehli, C., Babarro, I., Fernández‐Somoano, A., & Tardón, A. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18094774 · Cited by 15
Sanders, N., Buraundi, S., Balic, A., Southwell, B. R., & Hutson, J. M. (2011) · The Journal of Urology · doi:10.1016/j.juro.2011.04.012 · Cited by 16
Endocrine Disruptors: Time to Act
Fernández, M. F., Román, M., Arrebola, J. P., & Olea, N. (2014) · Current Environmental Health Reports · doi:10.1007/s40572-014-0025-9 · Cited by 16
Comparative testis structure and function in three representative mice strains
de Oliveira, C. F. A., Lara, N. D. L. E. M., Cardoso, B. R. L., França, L. R., & de Avelar, G. F. (2020) · Cell and Tissue Research · doi:10.1007/s00441-020-03239-0 · Cited by 16
“In this regard, the Swiss mice reduced anogenital index is an intriguing finding that is difficult to interpret, requiring further studies aiming to investigate if this mice strain is less exposed to androgens during the MPW.”
InfluentialBalic, A., Nation, T. R., Buraundi, S., Farmer, P. J., Newgreen, D. F., Southwell, B. R., & Hutson, J. M. (2010) · Journal of Pediatric Surgery · doi:10.1016/j.jpedsurg.2009.10.088 · Cited by 16
“The strain also carried a coat-colour marker to identify the affected animals [9].”
Exposure to polychlorinated compounds and cryptorchidism; A nested case-control study
Axelsson, J., Scott, K., Dillner, J., Lindh, C. H., Zhang, H., Rylander, L., & Rignell‐Hydbom, A. (2020) · PLoS ONE · doi:10.1371/journal.pone.0236394 · Cited by 15
Draskau, M. K., Rosenmai, A. K., Scholze, M., Pedersen, M., Boberg, J., Christiansen, S., & Svingen, T. (2021) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2021.115554 · Cited by 15
Amato, C. M., Yao, H. H., & Zhao, F. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.910964 · Cited by 15
Luan, M., Liang, H., Chen, Y., Chen, D., Ji, H., Chen, H., Miao, M., & Yuan, W. (2022) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2022.159050 · Cited by 15
Gómez, C. E. L., Farías, P., Moreno-Macías, H., Romano-Riquer, S. P., & Riojas‐Rodríguez, H. (2017) · Reproductive Toxicology · doi:10.1016/j.reprotox.2017.08.011 · Cited by 15
Rehman, H., Jahan, S., Ullah, I., Thörnqvist, P.-O., Jabbar, M. W., Shoaib, M., Aman, F., & John, N. E. (2020) · Human & Experimental Toxicology · doi:10.1177/0960327120911416 · Cited by 15
van den Driesche, S., Shoker, S., Inglis, F., Palermo, C. M., Langsch, A., & Otter, R. (2020) · Toxicology Letters · doi:10.1016/j.toxlet.2020.10.006 · Cited by 15
Makris, S. L., Euling, S. Y., Gray, L. E., Benson, R., & Foster, P. M. D. (2010) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2010.09.006 · Cited by 15
Jørgensen, K. T., Lindhard, M. S., Toft, G. V., Larsen, A. D., Bonde, J. P., & Hougaard, K. S. (2012) · Scandinavian Journal of Work Environment & Health · doi:10.5271/sjweh.3330 · Cited by 15
Investigation of sexual dimorphisms through mouse models and hormone/hormone-disruptor treatments
Ipulan, L. A., Raga, D., Suzuki, K., Murashima, A., Matsumaru, D., Cunha, G. R., & Yamada, G. (2015) · Differentiation · doi:10.1016/j.diff.2015.11.001 · Cited by 15
Regulation of mRNA Translation Is a Novel Mechanism for Phthalate Toxicity
Ling, J., Lopez-Dee, Z. P., Cottell, C., Wolfe, L. G., & Nye, D. M. R. (2016) · PLoS ONE · doi:10.1371/journal.pone.0167914 · Cited by 15
In utero exposure to hexavalent chromium disrupts rat fetal testis development
Zheng, W., Ge, F., Wu, K., Chen, X., Li, X., Chen, Y., Lv, Y., Lian, Q., & Ge, R. (2018) · Toxicology Letters · doi:10.1016/j.toxlet.2018.10.010 · Cited by 15
Male genital abnormalities in intrauterine growth restriction
Nemec, S. F., Nemec, U., Brugger, P. C., Bettelheim, D., Weber, M., Graham, J. M., Rimoin, D. L., & Prayer, D. (2012) · Prenatal Diagnosis · doi:10.1002/pd.3831 · Cited by 15
Lu, C., Wen, H., Chen, M.-L., Sun, C.-W., Hsieh, C., Wu, M., Wang, S., & TMICS study group (2024) · PLoS ONE · doi:10.1371/journal.pone.0297631 · Cited by 14
Olmos‐Ortiz, A., García‐Quiroz, J., Halhali, A., Avila, E., Zaga‐Clavellina, V., Chavira‐Ramírez, R., Garcı́a-Becerra, R., Caldiño‐Soto, F., Larrea, F., & Dı́az, L. (2018) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2018.10.009 · Cited by 14
Developmental mutant mouse models for external genitalia formation
Hashimoto, D., Hyuga, T., Acebedo, A. R., Alcantara, M. C., Suzuki, K., & Yamada, G. (2018) · Congenital Anomalies · doi:10.1111/cga.12319 · Cited by 14
Development of the Penile Urethra in the Tammar Wallaby
Leihy, M. W., Shaw, G., Wilson, J. D., & Renfree, M. B. (2011) · Sexual Development · doi:10.1159/000334053 · Cited by 14
Probing the germline-dependence of epigenetic inheritance using artificial insemination in mice
Bohacek, J., von Werdt, S., & Mansuy, I. M. (2016) · Current Zoology · doi:10.1093/eep/dvv015 · Cited by 14
Mendiola, J., Oñate-Celdrán, J., Samper-Mateo, P., Árense-Gonzalo, J. J., Roca, M. T., Sánchez-Rodríguez, C., García-Escudero, D., Fontana‐Compiano, L. O., Eisenberg, M. L., Swan, S. H., et al. (2016) · Andrology · doi:10.1111/andr.12202 · Cited by 14
Sheinberg, R., Siegel, E., Keidar, R., Mandel, D., Lubetzky, R., Kohn, E., Livne, A., Tovbin, J., Betser, M., Moskovich, M., et al. (2020) · Reproductive Toxicology · doi:10.1016/j.reprotox.2020.06.005 · Cited by 14
A novel biomarker for anti-androgenic activity in placenta reveals risks of urogenital malformations
Arrebola, J. P., Molina-Molina, J.-M., Fernández, M. F., Sáenz, J. M., Amaya, E., Indiveri, P., Hill, E. M., Scholze, M., Orton, F., Kortenkamp, A., et al. (2015) · Reproduction · doi:10.1530/rep-14-0525 · Cited by 14
McDonnell‐Dowling, K., & Kelly, J. P. (2015) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2015.12.003 · Cited by 13
Huang, L., Huang, S., Luo, X., Li, L., Chen, X., Zan, G., Tan, Y., Liu, C., Hou, Q., Ge, X., et al. (2020) · Environment International · doi:10.1016/j.envint.2020.105900 · Cited by 12
Borrow, A. P., Levy, M., Soehngen, E., & Cameron, N. M. (2013) · Journal of neuroendocrinology · doi:10.1111/jne.12035 · Cited by 13
Ryu, D. S., Cho, W. Y., Chung, J. M., Kang, D. I., Lee, S. D., & Park, S. (2018) · Korean journal of urology · doi:10.4111/icu.2018.59.1.55 · Cited by 13
Kızılay, D. Ö., Aydın, C., Aygün, A., Tuhan, H., & Olukman, Ö. (2020) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2020-0363 · Cited by 13
Kjersgaard, C. L., Arendt, L. H., Ernst, A., Lindhard, M. S., Olsen, J., Henriksen, T. B., Strandberg‐Larsen, K., & Ramlau-Hansen, C. H. (2022) · Clinical Epidemiology · doi:10.2147/clep.s335877 · Cited by 13
Cirillo, T., & Cocchieri, R. A. (2013) · Elsevier eBooks · doi:10.1533/9780857098917.2.334 · Cited by 13
On environmental threats to male infertility
Wilcox, A. J., & Bonde, J. P. (2013) · Asian Journal of Andrology · doi:10.1038/aja.2012.153 · Cited by 13
Su, S., Farmer, P. J., Li, R., Sourial, M., Buraundi, S., Bodemer, D., Southwell, B. R., & Hutson, J. M. (2012) · The Journal of Urology · doi:10.1016/j.juro.2012.02.041 · Cited by 13
Schneuer, F. J., Bower, C. I., Holland, A. J. A., Tasevski, V., Jamieson, S., Barker, A., Lee, L., Majzoub, J. A., & Nassar, N. (2016) · Human Reproduction · doi:10.1093/humrep/dew150 · Cited by 13
Evaluation of the effects of α-cypermethrin on fetal rat testicular steroidogenesis
Saillenfait, A., Sabaté, J., Denis, F., Antoine, G., Robert, A., Roudot, A., Ndiaye, D., & Eljarrat, E. (2017) · Reproductive Toxicology · doi:10.1016/j.reprotox.2017.06.133 · Cited by 13
Freire, C., Hernández, O. O., Dávila-Arias, C., Pérez‐Lobato, R., Calvente, I., Ramos, R., Olea, N., & Fernández, M. F. (2018) · Andrology · doi:10.1111/andr.12544 · Cited by 14
Schwartz, C. L., Vinggaard, A. M., Christiansen, S., Darde, T., Chalmel, F., & Svingen, T. (2019) · Toxicological Sciences · doi:10.1093/toxsci/kfz046 · Cited by 13
The evolution of hypospadias publications: A bibliometric approach
Doğan, G., & İpek, H. (2020) · Revista Internacional de Andrología · doi:10.1016/j.androl.2020.03.002 · Cited by 13
Barrett, E. S., Sharghi, S., Thurston, S. W., Terry, M. S., Loftus, C. T., Karr, C. J., Nguyen, R. H. N., Swan, S. H., & Sathyanarayana, S. (2023) · Environmental Health Perspectives · doi:10.1289/ehp12627 · Cited by 13
Endocrine disruption and human health effects—a call to action
Sharpe, R. M. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.165 · Cited by 12
Neonatal hypothyroidism does not increase Sertoli cell proliferation in iNOS−/− mice
Lara, N. D. L. E. M., & França, L. R. (2017) · Reproduction · doi:10.1530/rep-17-0111 · Cited by 12
Domenici, L., Musella, A., Bracchi, C., Lecce, F., Schiavi, M. C., Colagiovanni, V., Donato, V. D., Marchetti, C., Tomao, F., Palaia, I., et al. (2018) · Journal of Menopausal Medicine · doi:10.6118/jmm.2018.24.2.108 · Cited by 12
Androgens Upregulate Pathogen-Induced Placental Innate Immune Response
Vancolen, S. Y., Ayash, T. A., Segura, M., Allard, M., Robaire, B., & Sébire, G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094978 · Cited by 11
Bellingham, M., Evans, N. P., Lea, R. G., Padmanabhan, V., & Sinclair, K. D. (2024) · Annual Review of Animal Biosciences · doi:10.1146/annurev-animal-111523-102259 · Cited by 12
Luan, M., Ji, H., Miao, M., Liang, H., Wang, Z., Chen, Y., Chen, A., Cao, W., & Yuan, W. (2021) · International Journal of Hygiene and Environmental Health · doi:10.1016/j.ijheh.2021.113706 · Cited by 11
AOP key event relationship report: Linking androgen receptor antagonism with nipple retention
Pedersen, E. B., Christiansen, S., & Svingen, T. (2022) · Current Research in Toxicology · doi:10.1016/j.crtox.2022.100085 · Cited by 11
Maternal protein malnutrition: effects on prostate development and adult disease
Rinaldi, J. D. C., dos Santos, S. A. A., Colombelli, K. T., Birch, L. A., Prins, G. S., Justulin, L. A., & Felisbino, S. L. (2018) · Journal of Developmental Origins of Health and Disease · doi:10.1017/s2040174418000168 · Cited by 11
Tack, L. J. W., Praet, M. M., Dorpe, J. V., Haid, B., Buelens, S., Hoebeke, P. B., LAECKE, E. V., Cools, M., & Spinoit, A. (2019) · Journal of Pediatric Urology · doi:10.1016/j.jpurol.2019.10.031 · Cited by 11
Wu, W., Ziglioli, F., & Maestroni, U. V. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.77761 · Cited by 11
Costa, N. O., Forcato, S., Cavichioli, A. M., Pereira, M. R. F., & Gerardin, D. C. C. (2020) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2020.115077 · Cited by 11
Kajioka, D., Suzuki, K., Matsushita, S., Hino, S., Sato, T., Takada, S., Isono, K., Takeo, T., Kajimoto, M., Nakagata, N., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2024067118 · Cited by 11
Androgen Regulates Dimorphic F-Actin Assemblies in the Genital Organogenesis
Liu, L., Suzuki, K., Chun, E., Murashima, A., Sato, Y., Nakagata, N., Fujimori, T., Yonemura, S., He, W., & Yamada, G. (2017) · Sexual Development · doi:10.1159/000477452 · Cited by 11
“Androgen actions are required in a specific time window, namely the masculinization programming window (MPW), to regulate multiple processes for the formation of male-type reproductive organs [Welsh et al., 2008, 2014].”
InfluentialAlbadawi, E. A., Alzaman, N. S., Elhassan, Y. H., Eltahir, H. M., Abouzied, M. M., & Albadrani, M. S. (2024) · Metabolites · doi:10.3390/metabo14090477 · Cited by 10
Martínez-Peña, A. A., Peña‐Castillo, A., Parra-Forero, L. Y., Hernández‐Ochoa, I., Hernández-Barrientos, L. R., Morimoto, S., & Mendoza-Rodríguez, C. A. (2019) · Reproductive Toxicology · doi:10.1016/j.reprotox.2019.04.005 · Cited by 10
O’Kelly, F., DeCotiis, K., Zu’bi, F., Farhat, W. A., & Koyle, M. A. (2019) · Pediatric Surgery International · doi:10.1007/s00383-019-04600-3 · Cited by 10
Low Perinatal Androgens Predict Recalled Childhood Gender Nonconformity in Men
Shirazi, T. N., Self, H., Rosenfield, K. A., Dawood, K., Welling, L., Cárdenas, R., Bailey, J., Balasubramanian, R., Delaney, A., Breedlove, S., et al. (2021) · Psychology Science · doi:10.1177/09567976211036075 · Cited by 10
Li, J., Yang, L., He, G., Wang, B., Miao, M., Ji, H., Wen, S., Cao, W., Yuan, W., & Liang, H. (2022) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2022.114130 · Cited by 10
Crouch, N. S., Michala, L., Creighton, S. M., & Conway, G. S. (2010) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.2010.02778.x · Cited by 10
Endocrine Disruption and Male Reproductive Health
Darbre, P. D. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-801139-3.00009-0 · Cited by 10
Maternal endometriosis and genital malformations in boys: a Danish register-based study
Arendt, L. H., Lindhard, M. S., Henriksen, T. B., Forman, A., Olsen, J., & Ramlau‐Hansen, C. H. (2017) · Fertility and Sterility · doi:10.1016/j.fertnstert.2017.07.009 · Cited by 10
dos Santos, S. A. A., Porto, E. M., Ribeiro, L. M., Rinaldi, J. D. C., Delella, F. K., Justulin, L. A., & Felisbino, S. L. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.10.022 · Cited by 10
Stretched penile length and its associations with testosterone and infertility
Slade, A. D., Christiansen, A. R., Keihani, S., Brant, W. O., & Hotaling, J. M. (2021) · Translational Andrology and Urology · doi:10.21037/tau-20-788 · Cited by 9
Hlisníková, H., Petrovičová, I., Kolena, B., Šidlovská, M., & Mlynček, M. (2021) · Reproductive Toxicology · doi:10.1016/j.reprotox.2021.04.001 · Cited by 10
Ovine fetal testis stage-specific sensitivity to environmental chemical mixtures
Lea, R. G., Mandon‐Pepin, B., Loup, B., Poumerol, E., Jouneau, L., Egbowon, B. F., Bowden, A., Cotinot, C., Purdie, L., Zhang, Z., et al. (2022) · Reproduction · doi:10.1530/rep-21-0235 · Cited by 11
“Furthermore, a common masculinisation programming period has been identified in rats that occurs just after testis differentiation (Welsh et al. 2008).”
Endocrine disrupters: we need research, biomonitoring and action
Andersson, A., Bay, K., Frederiksen, H. W., & Skakkebæk, N. E. (2016) · Andrology · doi:10.1111/andr.12244 · Cited by 10
Endogenous inhibins regulate steroidogenesis in mouse TM3 Leydig cells by altering SMAD2 signalling
Wang, Y., Bilandzic, M., Ooi, G. T., Findlay, J. K., & Stenvers, K. L. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.07.026 · Cited by 10
Curley, M. K., Gonzalez, Z. N., Milne, L., Hadoke, P. W. F., Handel, I. G., Péault, B., & Smith, L. B. (2019) · Scientific Reports · doi:10.1038/s41598-019-50855-0 · Cited by 10
Colicino, E., Cowell, W., Pedretti, N. F., Joshi, A., Petrick, L. M., Niedzwiecki, M. M., Wright, R. O., & Wright, R. J. (2023) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2023.106395 · Cited by 9
Svingen, T., Andersson, A., Angelova, J., Axelstad, M., Bakker, J., Baumann, L., Beronius, A., Bouftas, N., Chalmel, F., Christiansen, S., et al. (2024) · Open Research Europe · doi:10.12688/openreseurope.17319.1 · Cited by 9
Effects of hazardous chemicals on secondary sex ratio: A comprehensive review
Dermitzakis, I., Theotokis, P., Axarloglou, E., Delilampou, E., Μanthou, M. E., & Meditskou, S. (2024) · Chemosphere · doi:10.1016/j.chemosphere.2024.142467 · Cited by 9
Svingen, T. (2025) · Annales d Endocrinologie · doi:10.1016/j.ando.2025.101787 · Cited by 9
Chatziioannou, A. C., Myridakis, A., & Stephanou, E. G. (2025) · Toxics · doi:10.3390/toxics13121029 · Cited by 10
“…have associated phthalate exposure with adverse effects on reproductive and developmental health, including an increased risk of cancer and anti-androgenic effects on male reproductive development after prenatal exposure, such as undescended testes, asthma, and decreased testes weight [25,26].”
Gannon, A., Darbey, A. L., Chensee, G., Lawrence, B. M., O’Donnell, L., Kelso, J., Reed, N., Parameswaran, S., Smith, S. E., Smith, L. B., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315015 · Cited by 9
The anogenital ratio as an indicator of reproductive performance in dairy heifers
Beci, B., Eetvelde, M. V., Vanlommel, L., & OPSOMER, G. (2023) · Theriogenology · doi:10.1016/j.theriogenology.2023.07.019 · Cited by 9
Liu, X., Ding, D., Shen, M., Yan, D., & Guo, S. (2023) · Biomedicines · doi:10.3390/biomedicines11102618 · Cited by 9
Role of Nodal signalling in testis development and initiation of testicular cancer
Poulsen, K. H., & Jørgensen, A. (2019) · Reproduction · doi:10.1530/rep-18-0641 · Cited by 9
Forcato, S., Montagnini, B. G., de Góes, M. L. M., Novi, D. R. B. S., Kiss, A. C. I., Ceravolo, G. S., & Gerardin, D. C. C. (2019) · Reproductive Toxicology · doi:10.1016/j.reprotox.2019.04.009 · Cited by 9
Impact of maternal overweight on the sexual maturity of male offspring in rats
Galarza, R. A., Rhon‐Calderón, E. A., Bizzozzero-Hiriart, M., Meneghini, M. A., Cortez, A. E., Lux-Lantos, V. A., & Faletti, A. G. (2019) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2019.05.014 · Cited by 9
Tekin, K., Arslan, P., Çil, B., Filazı, A., Akçay, E., & Yurdakök-Di̇kmen, B. (2020) · Cytotechnology · doi:10.1007/s10616-020-00401-y · Cited by 9
Ramos, J. G., Silva, J. P. D. A., Manso, L. A., Rodrigues, G. A., Taboga, S. R., Carvalho, H. F., dos Santos, F. C. A., & Biancardi, M. F. (2020) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2020.104473 · Cited by 9
Palermo, C. M., Foreman, J. E., Wikoff, D. S., & Lea, I. A. (2021) · Current Research in Toxicology · doi:10.1016/j.crtox.2021.07.002 · Cited by 9
Collet, B., Desalegn, A. A., Swart, K., Naderman, M., Iszatt, N., Stigum, H., Jensen, T. K., Brouwer, A., Eggesbø, M. Å., & van der Burg, B. (2021) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2021.149746 · Cited by 9
The Impact of Activin A on Fetal Gonocytes: Chronic Versus Acute Exposure Outcomes
Moody, S. C., Whiley, P. A. F., Western, P. S., & Loveland, K. L. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.896747 · Cited by 10
“5 these testes exhibit an abnormal accumulation of lipid droplets within the testis cords and an elevated A4/T ratio (9), both indicating a profound impact of activin A signalling pathway on processes central to masculinization in a key developmental window (24).”
Anogenital distance as a measure of male competitive ability in Rwenzori Angolan colobus
Teichroeb, J. A., Stead, S. M., Edwards, P. D., Landry, F., Palme, R., & Boonstra, R. (2020) · American Journal of Primatology · doi:10.1002/ajp.23111 · Cited by 9
Tunc‐Ozcan, E., Ferreira, A., & Redei, E. E. (2016) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13090 · Cited by 9
“Only the expressions of Igf2 and Insr show sex differences in cultured hippocampal neurons, while more extensive sex differences were found in the fetal hippocampi harvested after the prenatal testosterone surge on GD18 to 19 (Welsh et al., 2008).”
Nepelska, M., Odum, J., & Munn, S. (2017) · Applied In Vitro Toxicology · doi:10.1089/aivt.2017.0004 · Cited by 9
“128 Therefore, the AOP focuses on the exposures within the MPW (15.5–18.5 GD days in rats).”
InfluentialHazards of Food Contact Material: Phthalates
Benson, R. W. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-378612-8.00219-5 · Cited by 9
Uldbjerg, C. S., Lim, Y., Beck, A. L., Petersen, J. H., Sorensen, K. M., Kristensen, D. M., Rantakokko, P., Coull, B. A., Lindh, C. H., Skakkebæk, N. E., et al. (2025) · Environment International · doi:10.1016/j.envint.2025.109762 · Cited by 9
“While timing of exposure is particularly relevant for TGCC, as the critical period of fetal masculinization occurs during 8–14 weeks (Welsh et al., 2008); our samples were collected close to this period, and longitudinal analyses show that PFAS levels are remarkably constant over months in an…”
Human Relevance of Rodent Leydig Cell Tumors
Steinbach, T., Maronpot, R. R., & Hardisty, J. F. (2015) · John Wiley & Sons, Inc. eBooks · doi:10.1002/9781118834015.ch109 · Cited by 8
Nation, T. R., Buraundi, S., Balic, A., Southwell, B. R., Newgreen, D. F., & Hutson, J. M. (2011) · Journal of Pediatric Surgery · doi:10.1016/j.jpedsurg.2010.11.035 · Cited by 8
“This gestational period is thought to be when masculinization of the GFN occurs [3], as it is when flutamide inhibits inguinoscrotal TD [8].”
Jeje, S. O., & Raji, Y. (2016) · Journal of Developmental Origins of Health and Disease · doi:10.1017/s2040174416000453 · Cited by 8
Scrotal base distance: A new key genital measurement in males with hypospadias and cryptorchidism
Abbas, T. O., & Ali, M. J. (2021) · Current Urology · doi:10.1097/cu9.0000000000000031 · Cited by 8
Identification and validation of reference genes for RT-qPCR analysis in fetal rat pancreas
Dai, Y., Kou, H., Guo, X.-L., Gong, Z., Liu, H., Liu, Y., Wang, H., & Guo, Y. (2021) · Reproductive Toxicology · doi:10.1016/j.reprotox.2021.09.009 · Cited by 8
The Impact of Nutrition and Environmental Epigenetics on Human Health and Disease
Tiffon, C. (2020) · Vide Leaf, Hyderabad eBooks · doi:10.37247/pamolscs.1.2020.18 · Cited by 8
Shen, X., Meng, X., Wang, C., Chen, X., Chen, Q., Cai, J., Zhang, J., Zhang, Q., & Fan, L. (2023) · Environmental Health · doi:10.1186/s12940-023-00969-w · Cited by 8
Metadata
- Authors
- Welsh, M., Saunders, P. T. K., Fisken, M., Scott, H. M., Hutchison, G. R., Smith, L. B., & Sharpe, R. M.
- Affiliations
- The Queen's Medical Research Institute (GB)
- Corresponding author
- Welsh, Michelle
- Venue
- Journal of Clinical Investigation
- Published
- 2008-04-01
- Volume
- 118
- Issue
- 4
- Pages
- 1479-1490
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2267017
- OpenAlex
- W2003163696
- Cited by
- 781
- References
- 61
- Citations by year
- 2026: 23 · 2025: 39 · 2024: 27 · 2023: 54 · 2022: 58 · 2021: 43 · 2020: 54 · 2019: 47 · 2018: 49 · 2017: 38 · 2016: 45 · 2015: 48 · 2014: 45 · 2013: 42 · 2012: 39
- FWCI
- 17.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Edinburgh Napier Research Repository (Edinburgh Napier University) (submittedVersion, cc-by-nc)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Medical Research Council
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Urology › Urological Disorders and Treatments
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Keywords
- fetal programming, hypospadias, cryptorchidism, testicular dysgenesis, androgen action, androgen receptor antagonists, androgens, anogenital distance, penile length, fetal development, pregnancy timing
- MeSH terms
- Androgens, Animals, Cryptorchidism, Embryo, Mammalian, Female, Gonads, Hypospadias, Male, Receptors, Androgen, Sex Characteristics, Sex Differentiation, Testosterone, Rats, Wistar, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
