Alterations in male rats following in utero exposure to betamethasone suggests changes in reproductive programming
Open accessAbstract
Antenatal betamethasone is used for accelerating fetal lung maturation for women at risk of preterm birth. Altered sperm parameters were reported in adult rats after intrauterine exposure to betamethasone. In this study, male rat offspring were assessed for reproductive development after dam exposure to betamethasone (0.1mg/kg) or vehicle on Days 12, 13, 18 and 19 of pregnancy. The treatment resulted in reduction in the offspring body weight, delay in preputial separation, decreased seminal vesicle weight, testosterone levels and fertility, and increased testicular weight. In the testis, morphologically abnormal seminiferous tubules were observed, characterized by an irregular cell distribution with Sertoli cell that were displaced towards the tubular lumen. These cells expressed both Connexin 43 (Cx43) and Proliferative Nuclear Cell Antigen (PCNA). In conclusion, intrauterine betamethasone treatment appears to promote reproductive programming and impairment of rat sexual development and fertility due to, at least in part, unusual testicular disorders.
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In utero betamethasone exposure acts mainly on the HPG axis, as the same pattern of hormonal alteration was observed in male and female pups and in the following two generations.
“Indeed, in utero betamethasone exposure confirmed its effects acting mainly on the HPG axis, since the same pattern of hormonal alteration was observed in both, male and female pups, as well as in the following two generations106–109.”
From Emerging insights into hypothalamic‐pituitary‐gonadal axis regulation and interaction with stress signalling (2018) · cites this paper as [108]
The Discussion (page unavailable) reports altered testosterone and LH levels in male offspring after in utero betamethasone exposure. It does not establish that the drug acts mainly on the HPG axis; it also discusses possible testicular alterations. The paper does not report the same hormonal pattern in female pups or across the following two generations. (LLM, conf=0.88)
Experimental — accuracy not yet measuredReduction of seminiferous tubule diameter and reduced T production were also observed after betamethasone exposure.
“Reduction of the seminiferous tubules diameter as well as reduced T production were also observed by Borges et al107,108.”
From Emerging insights into hypothalamic‐pituitary‐gonadal axis regulation and interaction with stress signalling (2018) · cites this paper as [108]
The Results report reduced seminiferous tubule diameter at both ages and lower serum testosterone at PND45 after prenatal betamethasone exposure. They report no testosterone difference at PND110. The paper measured circulating testosterone, not testosterone production directly, so the claim omits an important age qualifier and overstates what was measured. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIntrauterine betamethasone exposure promoted drastic alterations in seminiferous tubule morphology, compromising its cytoarchitecture and spermatogenesis.
“Moreover, the intrauterine exposure to betamethasone promoted drastic alterations in the seminiferous tubule morphology, compromising its cytoarchitecture and spermatogenesis108.”
From Emerging insights into hypothalamic‐pituitary‐gonadal axis regulation and interaction with stress signalling (2018) · cites this paper as [108]
The Results report abnormal seminiferous-tubule morphology, reduced tubule diameter, delayed germ-cell maturation, and fewer tubules at stages VII–VIII. But abnormalities affected approximately 20% of tubules; the paper says spermatogenesis remained active and cellular organization appeared maintained within the displaced cells. Thus, “drastic” disruption of cytoarchitecture and spermatogenesis overstates the findings. (LLM, conf=0.86)
Experimental — accuracy not yet measuredFetal programming by betamethasone exposure was seen at birth as low pup weight, at puberty as reduced serum T levels and delayed puberty onset, and at adulthood as effects on gonadal morphology and function, sperm quality, and fertility.
“Borges et al. reinforced these findings and also demonstrated that the impact of fetal programming promoted by betamethasone exposure was seen at birth, as low pup weight, at puberty, as reduced serum T levels and delayed puberty onset, and at adulthood, as direct effects on gonadal morphology and function, sperm quality and fertility106–108.”
From Emerging insights into hypothalamic‐pituitary‐gonadal axis regulation and interaction with stress signalling (2018) · cites this paper as [108]
The Results report lower offspring weight at PND1, delayed preputial separation and lower testosterone at PND45, as well as adult testicular abnormalities and reduced fertility. The Discussion links these findings to altered sperm quality, but describes reduced sperm quality as a possible explanation for the fertility result and refers to a previous study; this paper did not directly demonstrate a change in sperm quality. (LLM, conf=0.87)
Experimental — accuracy not yet measuredTreatment with glucocorticoids during a critical developmental window promotes alterations to the reproductive system in both male and female offspring that continue into adulthood.
“Overall, treatment with glucocorticoids during a critical window of development promotes alterations to the reproductive system, for both, male and female offspring, which continued into adulthood.”
From Emerging insights into hypothalamic‐pituitary‐gonadal axis regulation and interaction with stress signalling (2018) · cites this paper as [108]
The Discussion reports that betamethasone exposure during a sensitive developmental window caused reproductive alterations in male rat offspring that persisted into adulthood. The study assessed male offspring; our copy does not establish the claimed adult reproductive effects in female offspring. (LLM, conf=0.90)
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References 54 · Cited by 21
Research works printed but not linked: 2
- G.R.H. Klinefelter, R.A., Toxicology of the Male Excurrent Ducts and Accessory Sex Glands, in: K. K.S. (Ed.), Reproductive and Developmental Toxicology (1998), pp. 553-592.
- L.D.E. Russell, R.A., Sinha-Hikim, A.P., Clegg, E.D., in: C.R. Press (Ed.), Histological and Histopathological Evaluation of the Testis, Montreal, 1990, pp. 201-202.
- Authors
- Borges, C. S., Dias, A. F. M. G., Rosa, J. L., Silva, P. V., Silva, R. F., Barros, A. L., Sanabria, M., Guerra, M. T., Gregory, M., Cyr, D. G., & De G. Kempinas, W.
- Affiliations
- Universidade Estadual Paulista (Unesp) (BR)
- Institut National de la Recherche Scientifique (CA)
- Venue
- Reproductive Toxicology
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 63
- Pages
- 125-134
- ISSN
- 0890-6238 (ISSN-L)
- OpenAlex
- W2416459533
- Cited by
- 21
- References
- 54
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 2 · 2017: 3
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Reproductive Toxicology (publishedVersion, other-oa)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Americanae (AECID Library) (submittedVersion, other-oa)
- EspaceINRS (National Institute for Scientific Research (Canada)) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- FAPESP—The State of São Paulo Research Foundation (2012/25350-1, 2013/26557-1)
- CNPq—National Council for Scientific and Technological Development (308842/2013-8)
- FQRNT—The Fonds de recherche du Québec—Nature et technologies (155065-06)
- The Natural Sciences Research Council of Canada
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Keywords
- betamethasone, prenatal exposure, male reproductive development, fertility, testicular abnormalities, seminiferous tubules, Sertoli cells, connexin 43, PCNA, testosterone, preputial separation, glucocorticoids, rats
- MeSH terms
- Animals, Betamethasone, Body Weight, Female, Fertility, Male, Maternal-Fetal Exchange, Pregnancy, Prenatal Exposure Delayed Effects, Testis, Rats, Wistar, Connexin 43, Proliferating Cell Nuclear Antigen, Sexual Development, Fetal Development
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