Cited by 782Sexual Differentiation and DisordersUrological Disorders and TreatmentsEffects and risks of endocrine disrupting chemicals

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 access

Welsh, Michelle, Saunders, Philippa T.K., Fisken, Mark, Scott, Hayley M., Hutchison, Gary R., Smith, Lee B., Sharpe, Richard M.·2008·Journal of Clinical Investigation

DOI 10.1172/jci34241PMC PMC2267017

Open this paper in CoChat — free account Open PDF

Abstract

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.

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

Crossref · 10.1172/jci34241

Cites

63 of 63 references verified0 citation errors · 0 not checkable

Statistics

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

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
Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects: Opinion
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
Book review
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
Human 'testicular dysgenesis syndrome': a possible model using in-utero exposure of the rat to dibutyl phthalate
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

Flagged first, then by citations

Show all 61 references

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.

Sorted by citations

Items 501–600 of 782

Timing of pubertal development in boys born with cryptorchidism and hypospadias: a nationwide cohort study
Arendt, L. H., Ernst, A., Lauridsen, L. L. B., Brix, N., Olsen, J., & Ramlau‐Hansen, C. H. (2019) · Asian Journal of Andrology · doi:10.4103/aja.aja_3_19 · Cited by 8
Androgen receptor antagonist flutamide modulates estrogen receptor alpha expression in distinct regions of the hypospadiac rat penis
Elmelund, E., Draskau, M. K., Berg, M., Strand, I. W., Black, J. R., Axelstad, M., Pask, A. J., & Svingen, T. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1654965 · Cited by 7
“In humans, ER a protein expression is also restricted to speci ﬁ c regions of the developing penis, mainly around the preputial lamina and in the canalizing urethral plate from around gestational week 15 (11, 34), which is after the MPW in humans (suggested to be gestational weeks 8-14) (6, 35).”
Transcription factors dysregulated in three complex birth defects datasets
Chen, Z., Gao, Y., Xie, H., Huang, Y., Chen, F., & Lei, Y. (2022) · Reproductive and Developmental Medicine · doi:10.1097/rd9.0000000000000018 · Cited by 7
Anogenital distance in a cohort of 169 infant boys with uni- or bilateral cryptorchidism including 18 boys with vanishing testes
Cortes, D., Fischer, M. B., Hildorf, A. E., Clasen‐Linde, E., Hildorf, S. E., Juul, A., Main, K. M., & Thorup, J. M. (2024) · Human Reproduction · doi:10.1093/humrep/deae025 · Cited by 7
“This is in agreement with the hypothesis of AGD being determined in gestational week 8 to 14 and with testicular dysgenesis (Larsen, 1997; Welsh et al. , 2008).”
Influential
HSD17B1 Compensates for HSD17B3 Deficiency in Fetal Mouse Testis but Not in Adults
Junnila, A., Zhang, F., Nieto, G. M., Hakkarainen, J., Mäkelä, J., Ohlsson, C., Sipilä, P., & POUTANEN, M. H. (2024) · Endocrinology · doi:10.1210/endocr/bqae056 · Cited by 7
IMPACT OF REAL-LIFE ENVIRONMENTAL EXPOSURES ON REPRODUCTION: Biosolids and male reproduction
Bellingham, M., & Evans, N. P. (2024) · Reproduction · doi:10.1530/rep-24-0119 · Cited by 7
The impact of impaired intrauterine growth on male fertility: A systematic review and meta‐analysis
Meng, F., Yao, M., Li, S., Tian, A., Zhang, C., & Luo, X. (2024) · Andrology · doi:10.1111/andr.13690 · Cited by 8
Reconstitution of rat fetal testis during the masculinisation programming window induces focal dysgenesis consistent with testicular dysgenesis syndrome
Smart, E., Macdonald, J., Smith, L. B., & Mitchell, R. T. (2020) · Scientific Reports · doi:10.1038/s41598-020-75803-1 · Cited by 7
Associations of maternal anthropometrics with newborn anogenital distance and the 2:4 digit ratio
Kloboves, M. E., Pacyga, D. C., Gardiner, J. C., Flaws, J. A., Schantz, S. L., & Strakovsky, R. S. (2022) · Human Reproduction · doi:10.1093/humrep/deac143 · Cited by 7
Evaluation of di-n-butyl phthalate reproductive toxicity in pregnant rats and their offspring and assessment of vitamin E administration in reducing toxicity.
Heidari, T., Batavani, R. A., Malekinejad, H., & Hobbenaghi, R. (2022) · PubMed Central · doi:10.30466/vrf.2020.118147.2806 · Cited by 7
Anogenital Distance: Features, Measures, and Uses as a Biomarker for Toxicity In Utero
Svingen, T., Hass, U., Schwartz, C. L., & Christiansen, S. (2023) · Biomarkers in disease · doi:10.1007/978-3-031-07392-2_37 · Cited by 7
Imprinting and Reproductive Health: A Toxicological Perspective
Chauhan, R., Archibong, A. E., & Ramesh, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242316559 · Cited by 7
Androgen/Wnt/β‐catenin signal axis augments cell proliferation of the mouse erectile tissue, corpus cavernosum
Kajimoto, M., Suzuki, K., Ueda, Y., Fujimoto, K., Takeo, T., Nakagata, N., Hyuga, T., Isono, K., & Yamada, G. (2022) · Congenital Anomalies · doi:10.1111/cga.12465 · Cited by 7
Association of pre-pregnancy body mass index and gestational weight gain with neonatal anogenital distance in a Chinese birth cohort
Wang, Z., Niu, J., Ji, H., Miao, M., Yang, L., Chen, X., Li, X., Song, X., Chen, A., Liang, H., et al. (2022) · Reproductive Health · doi:10.1186/s12978-022-01458-y · Cited by 7
“In humans, shorter AGD has been associated with adverse reproductive outcomes, including poorer semen quality [15], lower female fertility [16], undescended testis [17], and hypospadias [18], suggesting that AGD could be a good indicator of neonatal and adult reproductive function [19].”
Les phtalates dans les dispositifs médicaux destinés à la nutrition artificielle
Bagel, S., Décaudin, B., Neuville, S., Chopineau, J., Odou, P., & Sautou, V. (2011) · Nutrition Clinique et Métabolisme · doi:10.1016/j.nupar.2010.11.001 · Cited by 7
Methodology for developing data-rich Key Event Relationships for Adverse Outcome Pathways exemplified by linking decreased androgen receptor activity with decreased anogenital distance
Holmer, M. L., Zilliacus, J., Draskau, M. K., Hlisníková, H., Beronius, A., & Svingen, T. (2024) · Reproductive Toxicology · doi:10.1016/j.reprotox.2024.108662 · Cited by 6
Correlation of anogenital distance from childhood to age 9 years—a prospective population-based birth cohort—the Odense Child Cohort
Andreasen, S. M., Gehrt, L., Hagen, C. P., Juul, A., Mola, G., Fischer, M. B., Andersen, M., Kristensen, D. M., & Jensen, T. K. (2024) · Human Reproduction Open · doi:10.1093/hropen/hoae050 · Cited by 6
Environmental interference and declining male fertility
Lea, R. G. (2025) · Reproduction Fertility and Development · doi:10.1071/rd25047 · Cited by 6
Evaluation of the testis function of mice exposed in utero and during lactation to Pfaffia glomerata (Brazilian ginseng)
Auharek, S. A., Carollo, C. A., Oliveira, R. J., Cunha‐Laura, A. L., Monreal, A. C. D., de Siqueira, J. M., Costa, D. S., Condé, T. R. D. P., Wollf, D. I. L., & Amaral, E. A. (2019) · Andrologia · doi:10.1111/and.13328 · Cited by 6
“Investigations in rodents and humans suggest that anogenital distance and penis size provide an excellent idea of the exposure to androgens and their action during intrauterine life (Sharpe, 2011; Welsh et al., 2008).”
Does anogenital distance change with age?
Toprak, T., & Tokat, E. (2019) · Andrologia · doi:10.1111/and.13431 · Cited by 6
Maternal CBZ exposure impairs testicular development, spermatogenesis and sperm parameters in male offspring at puberty
de Oliva, S. U., Engelbrecht, R. D. M., & Miraglia, S. M. (2020) · Andrologia · doi:10.1111/and.13657 · Cited by 6
Repression of Mafb promotes foreskin fibroblast proliferation through upregulation of CDK2, cyclin E and PCNA
Kong, X., Liu, Z., Long, C., Shen, L., Liu, X., & Wei, G. (2022) · Andrologia · doi:10.1111/and.14411 · Cited by 6
Cocktails of NSAIDs and 17α Ethinylestradiol at Environmentally Relevant Doses in Drinking Water Alter Puberty Onset in Mice Intergenerationally
Philibert, P., Déjardin, S., Girard, M., Durix, Q., Gonzalez, A., Mialhe, X., Tardat, M., Poulat, F., & Boizet‐Bonhoure, B. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065890 · Cited by 6
Placental pathology and hypospadias
Chen, Y., Sun, L., Geng, H., Lei, X., & Zhang, J. (2016) · Pediatric Research · doi:10.1038/pr.2016.246 · Cited by 6
Oral contraceptive use and genital anomalies in sons. A Danish cohort study
Buur, L., Laurberg, V., Ernst, A., Arendt, L. H., Andersen, A.-M. N., Olsen, J., & Ramlau‐Hansen, C. H. (2019) · Reproductive Toxicology · doi:10.1016/j.reprotox.2019.07.004 · Cited by 6
Endocrine-disrupting Chemicals (EDCs) in Mammals
Pelch, K. E., Beeman, J. M., Niebruegge, B. A., Winkeler, S. R., & Nagel, S. C. (2011) · Elsevier eBooks · doi:10.1016/b978-0-12-374932-1.00061-5 · Cited by 6
Reference Values for and Correlation Analysis of the Anogenital Distance of Chinese Han Full-Term Singleton Neonates
Cao, W., Ding, X., Dong, Z., & Tang, H. (2022) · Frontiers in Pediatrics · doi:10.3389/fped.2022.905421 · Cited by 6
“genital development, resulting in reproductive malformations such as short AGD, hypospadias, and cryptorchidism (2, 3).”
Environmental Influences on Male Reproductive Health
Brinkworth, M. H., & Handelsman, D. J. (2010) · Springer eBooks · doi:10.1007/978-3-540-78355-8_19 · Cited by 6
Developmental genetics of the male reproductive system
O'Neill, M. A., Ruthig, V. A., Haller, M., Zhelyazkova, B. H., White, J. T., Thirumavalavan, N., & Lamb, D. J. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-91380-5.00021-6 · Cited by 5
Development and verification of machine learning model based on anogenital distance, penoscrotal distance, and 2D:4D finger ratio before puberty to predict hypospadias classification
He, Z., Yang, B., Tang, Y., & Wang, X. (2024) · Frontiers in Pediatrics · doi:10.3389/fped.2024.1297642 · Cited by 5
Hypospadias: One Defect, Multiple Causes, Acting Through Shared Pathways
Palmsten, K. K., & Chambers, C. (2015) · Current Epidemiology Reports · doi:10.1007/s40471-014-0034-0 · Cited by 5
Perturbateurs endocriniens environnementaux et fertilité
Gaspari, L., Paris, F., Soyer‐Gobillard, M., Kalfa, N., Sultan, C., & Hamamah, S. (2021) · Gynécologie Obstétrique Fertilité & Sénologie · doi:10.1016/j.gofs.2021.09.009 · Cited by 5
A Comparative Multi-System Approach to Characterizing Bioactivity of Commonly Occurring Chemicals
Rivera, B. N., Wilson, L. B., Kim, D. N., Pande, P., Anderson, K. A., Tilton, S. C., & Tanguay, R. L. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19073829 · Cited by 5
Maternal Protein Restriction Alters the Expression of Proteins Related to the Structure and Functioning of the Rat Offspring Epididymis in an Age-Dependent Manner
Cavariani, M. M., Santos, T. D. M., Chuffa, L. G. D. A., Pinheiro, P. F. F., Scarano, W. R., & Domeniconi, R. F. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.816637 · Cited by 5
The alternate pathway of androgen metabolism and window of sensitivity
Renfree, M. B., & Shaw, G. (2023) · Journal of Endocrinology · doi:10.1530/joe-22-0296 · Cited by 6
Maternal Bereavement and Cryptorchidism in Offspring
Ingstrup, K. G., Olsen, J., Wu, C. S., Nohr, E. A., Bech, B. H., Li, J., Susser, E., & Lindhard, M. S. (2014) · Epidemiology · doi:10.1097/ede.0000000000000194 · Cited by 5
An immunohistochemical analysis of the effects of androgen receptor knock out on gubernacular differentiation in the mouse
Perera, N., Szarek, M., Vannitamby, A., Vikraman, J., Huan, G., Durston, A., Hutson, J., & Li, R. (2017) · Journal of Pediatric Surgery · doi:10.1016/j.jpedsurg.2017.11.063 · Cited by 5
Testosterone therapy in children and adolescents: to whom, how, when?
Arbeláez, M. C. S., Israeli, J. M., Kresch, E., Telis, L., & Nassau, D. E. (2022) · International Journal of Impotence Research · doi:10.1038/s41443-021-00525-5 · Cited by 5
Development and Characterization of Cell-Specific Androgen Receptor Knockout Mice
O’Hara, L., & Smith, L. B. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-3724-0_14 · Cited by 5
In Utero Exposure to Environmental Chemicals: Lessons from Maternal Cigarette Smoking and Its Effects on Gonad Development and Puberty
McKinlay, R., O’Shaughnessey, P., Sharpe, R. M., & Fowler, P. (2011) · Humana Press eBooks · doi:10.1007/978-1-60761-561-3_2 · Cited by 4
Reduced Expression of Androgen Receptor and Myosin Heavy Chain mRNA in Cremaster Muscle of Boys with Nonsyndromic Cryptorchidism
Barthold, J. S., Wang, Y., Reilly, A., Robbins, A. K., Figueroa, T. E., BaniHani, A. H., Hagerty, J. A., & Akins, R. E. (2012) · The Journal of Urology · doi:10.1016/j.juro.2012.06.033 · Cited by 5
Effects of Vitamin D Restricted Diet Administered during Perinatal and Postnatal Periods on the Penis of Wistar Rats
Fernandes-Lima, F., Gregório, B. M., Nascimento, F. A. M., Costa, W. S., GALLO, C. B. M., & Sampaio, F. J. B. (2018) · BioMed Research International · doi:10.1155/2018/6030646 · Cited by 5
Low Sperm Counts May Be Preventable
Sharpe, R. M. (2011) · Science · doi:10.1126/science.333.6048.1380-b · Cited by 5
WITHDRAWN: Prenatal exposure to perfluoroalkyl substances and anogenital distance at 3 months of age as marker of endocrine disruption
Lind, D. V., Priskorn, L., Lassen, T. H., Nielsen, F., Kyhl, H. B., Kristensen, D. M., Christesen, H. T., Steener, J., Grandjean, P., & Jensen, T. K. (2016) · Reproductive Toxicology · doi:10.1016/j.reprotox.2016.07.008 · Cited by 5
“AGD is considered a sensitive marker of fetal androgen exposure, and reductions in this distance may therefore indicate anti-androgenic action during early stages of development of male reproductive organs (Welsh et al., 2008).”
Retracted
Effects of maternal poor ovarian response on the reproductive endocrine profiles of the next generation: a prospective cohort study in China
Feng, W., Ren, Y., Zhou, J., Zhu, H., Zhao, H., Qin, Y., Li, J., Xia, M., Xu, L., Li, M., et al. (2025) · Human Reproduction Open · doi:10.1093/hropen/hoaf019 · Cited by 4
“…androgen exposure may affect the masculinization of the genitalia in male offspring, including increased risk of hypospadias and cryptorchidism, as well as a decreased anogenital distance (Menon and Khatwa, 2000; Dom � ınguez-Salazar et al. , 2002; Welsh et al. , 2008; Sunman et al. , 2019).”
Single-cell resolution uncovers neighboring cell subtypes that share steroidogenic capacity during fetal testis development
Jiang, K., Fu, Z., Tsourkas, P. K., Kothandapani, A., Kearse, T. W., McIlwain, S. J., Mayère, C., Nef, S., & Jorgensen, J. S. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2501392122 · Cited by 4
AOP report: adverse outcome pathway network for developmental androgen signaling inhibition leading to short anogenital distance in male offspring
Svingen, T., Elmelund, E., Holmer, M. L., Bindel, A. O., Holbech, H., & Draskau, M. K. (2025) · Environmental Toxicology and Chemistry · doi:10.1093/etojnl/vgaf221 · Cited by 4
Association of exposure to prenatal perﬂuoroalkyl substances and estrogen receptor 1 polymorphisms with the second to fourth digit ratio in school-aged children: The Hokkaido study
Nishimura, Y., Moriya, K., Kobayashi, S., Araki, A., Sata, F., Mitsui, T., Itoh, S., Miyashita, C., Cho, K., Kon, M., et al. (2022) · Reproductive Toxicology · doi:10.1016/j.reprotox.2022.02.002 · Cited by 4
Exploratory Assessment of Interunit Dominance Relationships in a Rwenzori colobus (Colobus angolensis ruwenzorii) Multilevel Society: The Importance of Social Network Position
Teichroeb, J. A., Huang, P., Adams, F. V., Habumuremyi, S., Mujjuzi, E., & Landry, F. (2024) · International Journal of Primatology · doi:10.1007/s10764-024-00444-4 · Cited by 4
Testicular toxicity in mice exposed to terephthalic acid in utero and during lactation
Monteiro, G. N., Monteiro, D. S., de Oliveira, R. C., Cunha‐Laura, A. L., Amaral, E. A., & Auharek, S. A. (2023) · Environmental Science and Pollution Research · doi:10.1007/s11356-023-26849-x · Cited by 4
Long exposure to a mixture of endocrine disruptors prediposes the ventral prostate of rats to preneoplastic lesions
Sousa, T. C., de Souza, L. P., Ricardo, M. L. S., Yoshigae, A. Y., Hinokuma, K. D., Gorzoni, A. B. R., de Aquino, A. M., Scarano, W. R., Castillho, A. C. D., Tavares, M. E. A., et al. (2023) · Environmental Science and Pollution Research · doi:10.1007/s11356-023-29768-z · Cited by 4
Longitudinal Evaluation of Fetal and Infant AGD in Healthy Children: Association With Penile Size, Testosterone, and DHT
Fischer, M. B., Mola, G., Priskorn, L., Scheel, L., Hegaard, H. K., Sundberg, K., Frederiksen, H. W., Andersson, A., Juul, A., & Hagen, C. P. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae342 · Cited by 5
Development and maturation of the normal male reproductive system
Sharpe, R. M. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511674686.005 · Cited by 4
Comparability between adult female anogenital distance and perineal measurements standardized by POP‐Q system (GH and PB)
Sánchez-Ferrer, M. L., Prieto‐Sánchez, M. T., Moya-Jiménez, L. C., Adoamnei, E., Mendiola, J., & Torres-Cantero, A. M. (2018) · Neurourology and Urodynamics · doi:10.1002/nau.23798 · Cited by 4
No difference in cognitive performance or gender role behavior between men with and without hypospadias
Strandqvist, A., Örtqvist, L., Frisén, L., Nordenskjöld, A., Herlitz, A., & Nordenström, A. (2019) · Hormones and Behavior · doi:10.1016/j.yhbeh.2019.02.004 · Cited by 4
“In rats, this has been shown to depend on androgen action during a temporally restricted “sensitive period”, corresponding to 8–14 weeks in human development (Welsh et al., 2008).”
In-utero Exposure to Maternal Stressful Life Events and Risk of Cryptorchidism: The Raine Study
Bräuner, E. V., Hickey, M., Hansen, Å. M., Doherty, D. A., Handelsman, D. J., Juul, A., & Hart, R. J. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00530 · Cited by 4
Prenatal Exposure to Endocrine Disrupting Chemicals and Their Effect on Health Later in Life
Engdahl, E., & Rüegg, J. (2020) · Springer eBooks · doi:10.1007/978-3-030-35213-4_4 · Cited by 5
Sulfasalazine exposure during pregnancy and lactation induces alterations in reproductive behavior in adult female rat offspring
Forcato, S., Aquino, A., Camparoto, N. D. M., Lens, H. H. M., Guarnier, F. A., Kiss, A. C. I., & Gerardin, D. C. C. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120303 · Cited by 4
Exposure to the Organophosphate Pesticide Fenitrothion Directly Induced Defects in Mouse Embryonic External Genitalia
Acebedo, A. R., Alcantara, M. C., Nakanishi, T., Ogawa, T., Yamada, G., & Suzuki, K. (2022) · Toxicological Sciences · doi:10.1093/toxsci/kfac085 · Cited by 4
Sulfasalazine exposure during pregnancy and lactation: reproductive outcomes in male rat offspring
Forcato, S., Aquino, A., Borges, L. I., Thomé, M. L. F. L., Bilibio, J. O., Lens, H. H. M., Erthal, R. P., Guarnier, F. A., Fernandes, G. S. A., & Gerardin, D. C. C. (2023) · Reproduction Fertility and Development · doi:10.1071/rd22240 · Cited by 4
Environmental Causes of Testicular Dysfunction
Sharpe, R. M. (2017) · Springer eBooks · doi:10.1007/978-3-319-53298-1_14 · Cited by 4
Long-term under-masculinization in male rabbits due to maternal stress is reversed by prenatal administration of testosterone
Bánszegi, O., Szenczi, P., Dúcs, A., Hudson, R., & Altbäcker, V. (2015) · Behavioural Processes · doi:10.1016/j.beproc.2015.03.013 · Cited by 4
Tératozoospermie : mythe ou réalité ? Étude d’une cohorte de 101 404 examens de sperme
Prisant, N., Cohen-Bacrie, P., Amar, E., Belaisch-Allart, J. C., Cohen-Bacrie, M., Olivennes, F. J., Aubriot, F.-X., & Belloc, S. (2011) · Gynécologie Obstétrique & Fertilité · doi:10.1016/j.gyobfe.2010.11.005 · Cited by 4
Neurotrophin signaling in a genitofemoral nerve target organ during testicular descent in mice
Cousinery, M., Li, R., Vannitamby, A., Vikraman, J., Southwell, B. R., & Hutson, J. M. (2015) · Journal of Pediatric Surgery · doi:10.1016/j.jpedsurg.2015.11.009 · Cited by 4
Retardation of Preputial Wound Healing in Rats with Hypospadias Induced by Flutamide
Zhou, Y., Peng, J., Cao, X., Yan, C., Huang, F., Shen, L., Long, C., Liu, X., & Wei, G. (2018) · Journal of Investigative Surgery · doi:10.1080/08941939.2018.1483448 · Cited by 4
Origin of Testicular Dysgenesis Syndrome Disorders in the Masculinization Programming Window: Relevance to Final Testis Size (=Sperm Production)
Sharpe, R. M., Auharek, S. A., Scott, H. M., França, L. R., Drake, A. J., & van den Driesche, S. (2011) · Research and perspectives in endocrine interactions · doi:10.1007/978-3-642-22775-2_11 · Cited by 4
“Although we have shown both of these concepts in earlier studies (Welsh et al. 2008; Scott et al. 2008; Drake et al. 2009), the present data go some way beyond these earlier studies because they are more detailed and involve a much wider spectrum of experimental treatments.”
Influential
Trends in Male Reproductive Health and Decreasing Fertility: Possible Influence of Endocrine Disrupters
Lassen, T. H., Iwamoto, T., Jensen, T. K., & Skakkebæk, N. E. (2014) · Springer eBooks · doi:10.1007/978-94-017-9226-4_7 · Cited by 4
Evolution and Prenatal Development
Coall, D. A., Callan, A. C., Dickins, T. E., & Chisholm, J. S. (2015) · Wiley eBooks · doi:10.1002/9781118963418.childpsy303 · Cited by 4
Biological Approaches to Studying Gender Development
Pasterski, V., & Bibonas, D. (2022) · Focus on sexuality research · doi:10.1007/978-3-030-84273-4_3 · Cited by 2
Toxicokinetics and reproductive toxicity of maternal bisphenol AF exposure during gestation in offspring of Sprague Dawley rats
Zhu, Y., Liu, X., Liu, X., Shi, Y., Li, H., Ru, S., & Tian, H. (2025) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2025.111424 · Cited by 3
Flame retardant tricresyl phosphate gestational exposure induced endocrine and metabolic disruptions in rat
Valentino, S., Sabaté, J., Perceau, M., Viton, S., Grossmann, S., Mascherin, M., Rousseau‐Ralliard, D., Ndiaye, D., Cosnier, F., & Gaté, L. (2025) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2025.117493 · Cited by 3
The relationship between anogenital distance and benign prostate hyperplasia‐related lower urinary tract symptoms
Kutluhan, M. A., Şahin, A., Ürkmez, A., Toprak, T., Akgül, K. T., Topaktaş, R., Sertkaya, Z., & Verit, A. (2020) · Andrologia · doi:10.1111/and.13589 · Cited by 3
Anogenital distance and anal position index in cadaveric human fetuses
Taşkınlar, H., Elvan, Ö., İşbir, C., KILLI, İ., & Naycı, A. (2022) · Anatomical Science International · doi:10.1007/s12565-022-00680-9 · Cited by 3
Deletion of GABAB receptors from Kiss1 cells affects glucose homeostasis without altering reproduction in male mice
Giorgio, N. P. D., Bizzozzero-Hiriart, M., Surkin, P. N., Repetto, E. M., Bonaventura, M. M., Tabares, F. N., Bourguignon, N. S., Converti, A., Gómez, J. M. R., Bettler, B., et al. (2023) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00129.2022 · Cited by 3
Hypospadias
Mouriquand, P. D. E., Gorduza, D. B., & Mure, P. (2023) · Springer eBooks · doi:10.1007/978-3-662-43567-0_191 · Cited by 3
Evaluation of the endocrine disrupting potential of Di-isodecyl phthalate
Lea, I. A., Feifarek, D. J., Mihalchik, A., Heintz, M. M., Haws, L. C., Nyambego, H., Goyak, K. O., Palermo, C. M., & Borghoff, S. J. (2025) · Current Research in Toxicology · doi:10.1016/j.crtox.2025.100221 · Cited by 3
“Rat phthalate syndrome can be experimentally induced in rats by exposure to chemicals that block androgen synthesis or action during the embryonic period, GD 15.5 – 18.5 in rat (van den Driesche et al., 2017; Welsh et al., 2008).”
Influential
I am a child, i learn through play; play-based character education
GÖRÜN, L., Kaya, H. B., ALPER, R., Koç, M., Çelen, A., Akpınar, S., Pepe, Ş., & Eskicioğlu, Y. E. (2025) · Frontiers in Psychology · doi:10.3389/fpsyg.2025.1613650 · Cited by 3
Testicule non descendu
Hameury, F., Nicolino, M. P., & Mouriquand, P. D. E. (2012) · EMC - Pédiatrie - Maladies infectieuses · doi:10.1016/s1637-5017(12)49642-9 · Cited by 3
Transabdominal Migration of the Testis
Hutson, J. M., Thorup, J. M., & Beasley, S. W. (2015) · Springer eBooks · doi:10.1007/978-3-319-25910-9_2 · Cited by 3
Altérations environnementales du développement du testicule foetal: zoom sur les phtalates
Habert, R., Muczynski, V., Lehraiki, A., Moison, D., Lambrot, R., Levacher, C., Lécureuil, C., Frydman, R., & Rouiller, V. (2011) · Basic and Clinical Andrology · doi:10.1007/s12610-011-0121-8 · Cited by 3
Disorders of sex development—the tip of the iceberg?
Juul, A., Main, K. M., & Skakkebæk, N. E. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.115 · Cited by 3
¿Son las hipospadias la expresión de diferentes enfermedades? MAMLD1 : un nuevo gen candidato para hipospadias
Fernández, N., Pérez, J., & Zarante, I. (2015) · Revista Urología Colombiana / Colombian Urology Journal · doi:10.1016/j.uroco.2015.06.005 · Cited by 3
Androgen Receptor Genotype in Humans and Susceptibility to Endocrine Disruptors
Giwercman, Y. L. (2016) · Hormone Research in Paediatrics · doi:10.1159/000443686 · Cited by 3
Human risk assessment of single exposure in chemical incidents
Bos, P. M. J., Ruijten, M., Bull, S., Nielsen, E., Gundert‐Remy, U., Wood, M. H., Vincent, J.-M., Santonen, T., & Leffler, P. E. (2012) · Toxicology Letters · doi:10.1016/j.toxlet.2012.03.467 · Cited by 3
Influencia de contaminantes ambientales en la gestación humana: Causante de patologías en el adulto
Tchernitchin, A. N., & Gaete, L. (2018) · Revista chilena de pediatría · doi:10.4067/s0370-41062018005001203 · Cited by 3
Estimations of total serum testosterone levels in Nigerian term neonates at birth using anogenital distance measurements
Kareem, A. J., Owa, J. A., & Elusiyan, J. B. E. (2020) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2019-0516 · Cited by 3
Anogenital distance in newborn infants conceived by assisted reproduction and natural conception
Erçin, S., Ertaş, S., Akın, O. D., Öktem, Ö., & Yakın, K. (2020) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2020.04.019 · Cited by 3
Endocrine-disrupting chemical removal by carbon nanocomposites
Hui, T., Ibrahim, N. A., Zhi, L. L., & Zaini, M. A. A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822121-1.00003-5 · Cited by 3
Environmental Phthalate Exposure in Relation to Reproductive Outcomes and Other Health Endpoints in Humans
Badroo, I. A., Khanday, A. H., Ali, Z. K., & Badroo, S. A. (2019) · Advances in environmental engineering and green technologies book series · doi:10.4018/978-1-5225-9452-9.ch015 · Cited by 3
Wolffian Duct Development
Hinton, B. T., & Avellar, M. C. W. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.64367-2 · Cited by 3
Phthalates mixtures in bottled water in Iran: human health risk assessment using direct and indirect exposure assessment
Jeddi, M. Z. (2018) · doi:10.18174/459150 · Cited by 3
Fetal programming by sodium saccharin and damage on male offspring reproductivePreprint
Godoi, A. R., Fioravante, V. C., Santos, B. M., Martinez, F. E., & Pinheiro, P. F. F. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.15.464538 · Cited by 3
Epididymis
Avellar, M. C. W., & Hinton, B. T. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.65180-2 · Cited by 3
Association of prenatal chlorpyrifos exposure with sexually dimorphic differences in anogenital distance among Thai farmworker children
Dang, T., Sehgal, N., Barr, D. B., Panuwet, P., Liang, D., Smarr, M. M., Naksen, W., Fiedler, N. L., Promkam, N., Prapamontol, T., et al. (2024) · Environmental Research · doi:10.1016/j.envres.2024.118325 · Cited by 2
Disruption of gonocyte development following neonatal exposure to di (2-ethylhexyl) phthalate
Reyes-Cruz, E., Rojas‐Castañeda, J. C., Landero‐Huerta, D. A., Hernández-Jardón, N., Reynoso-Robles, R., Mosqueda, M. D. L. J., Medrano, A., & Vigueras‐Villaseñor, R. M. (2024) · Reproductive Biology · doi:10.1016/j.repbio.2024.100877 · Cited by 2
Reproductive Hormones During Minipuberty Suggest Subtle Testicular Impairments in Boys With Hypospadias
Leunbach, T. L., Ernst, A., Johannsen, T. H., Berglund, A., Albrethsen, J., Frederiksen, H. W., Juul, A., & Rawashdeh, Y. F. (2025) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaf618 · Cited by 2
Anogenital Distance in Newborns with Hypospadias
Patil, S., Ghagane, S. C., Sharma, M., Rajendra, N., Pingale, N., & Gupta, P. (2021) · American Journal of Pediatrics · doi:10.11648/j.ajp.20210701.15 · Cited by 2
The use of anogenital distance as a non‐invasive predictor of seminal quality in captive squirrel monkey (Saimiri collinsiOsgood 1961)
Leão, D. L., Sampaio, W. V., Sousa, P. D. C., Oskam, I. C., dos Santos, R. R., & Domingues, S. F. S. (2021) · Journal of Medical Primatology · doi:10.1111/jmp.12541 · Cited by 2
Androgenic induction of penile features in postnatal female mouse external genitalia from birth to adulthood: Is the female sexual phenotype ever irreversibly determined?
Cunha, G. R., Cao, M., Derpinghaus, A., & Baskin, L. S. (2023) · Differentiation · doi:10.1016/j.diff.2023.02.001 · Cited by 2
Effects of Sex Hormones on Vascular Reactivity in Boys With Hypospadias
Lucas-Herald, A. K., Montezano, A. C. I., Alves-Lopes, R., Haddow, L., O’Toole, S., Flett, M. E., Lee, B., Amjad, S. B., Steven, M. J., McNeilly, J., et al. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad525 · Cited by 2

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
ORCID: Welsh, Michelle
Saunders, Philippa T.K.
Scott, Hayley M.
Smith, Lee B.
Sharpe, Richard M.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2008-04-01
Volume: 118
Issue: 4
Pages: 1479-1490
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci34241
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

Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks