Betamethasone causes intergenerational reproductive impairment in male rats

Borges, Cibele dos Santos; Pacheco, Tainá Louise; Silva, Katiussia Pinho da; Fernandes, Fábio Henrique; Gregory, Mary; Pupo, André S.; Salvadori, Daisy M.F.; Cyr, Daniel G.; Kempinas, Wilma De Grava

doi:10.1016/j.reprotox.2017.04.012

Cited by 7 publications

(7 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pedrana et al also observed that in utero betamethasone exposure directly affected the development of sheep testes, decreasing the size of the testicular cords and interstitial space, suggesting an impact on Leydig cells, since they express GR 110 . Reduction of the seminiferous tubules diameter as well as reduced T production were also observed by Borges et al 107,108 . Moreover, the intrauterine exposure to betamethasone promoted drastic alterations in the seminiferous tubule morphology, compromising its cytoarchitecture and spermatogenesis 108 .…”

Section: Stress and Reproduction: Bidirectional Interactionssupporting

confidence: 64%

Emerging insights into hypothalamic‐pituitary‐gonadal axis regulation and interaction with stress signalling

Acevedo-Rodriguez

Kauffman

Cherrington

et al. 2018

J Neuroendocrinology

141

132

View full text Add to dashboard Cite

Reproduction and fertility are regulated via hormones of the hypothalamic-pituitary-gonadal (HPG) axis. Control of this reproductive axis occurs at all levels, including the brain and pituitary, and allows for the promotion or inhibition of gonadal sex steroid secretion and function. In addition to guiding proper gonadal development and function, gonadal sex steroids also act in negative- and positive-feedback loops to regulate reproductive circuitry in the brain, including kisspeptin neurones, thereby modulating overall HPG axis status. Additional regulation is also provided by sex steroids made within the brain, including neuroprogestins. Furthermore, because reproduction and survival need to be coordinated and balanced, the HPG axis is able to modulate (and be modulated by) stress hormone signalling, including cortiscosterone, from the hypothalamic-pituitary-adrenal (HPA) axis. This review covers recent data related to the neural, hormonal and stress regulation of the HPG axis and emerging interactions between the HPG and HPA axes, focusing on actions at the level of the brain and pituitary.

show abstract

Section: Stress and Reproduction: Bidirectional Interactionssupporting

confidence: 64%

Emerging insights into hypothalamic‐pituitary‐gonadal axis regulation and interaction with stress signalling

Acevedo-Rodriguez

Kauffman

Cherrington

et al. 2018

J Neuroendocrinology

141

132

View full text Add to dashboard Cite

show abstract

“…Despite its beneficial effects on the fetal lung maturation (Jobe & Soll, ; Drake et al ., ), it is known to cause a reduction in fetal testosterone levels (Ward & Weisz, ; Corbier et al ., ; Page et al ., ; Hardy et al ., ). We have previously reported fetal reprogramming in the F1 and F2 generations of rats after gestational exposure to BM, characterized by altered testicular development and morphology and also impaired sperm quality and fertility (Borges et al ., , 2017a,b).…”

Section: Discussionmentioning

confidence: 99%

“…There are no studies showing the role of Cx43 in epididymis contractility; however, given the importance of Cx43 gap junctions in uterine contractions, it is likely to play a similar role in the epididymis. This could explain, at least in part, the effects of BM on increased sperm transit time in F1 and smaller ejaculation plugs in F2 previously observed (Borges et al ., , 2017a,b).…”

Section: Discussionmentioning

confidence: 99%

“…Rats received an intramuscular injection of vehicle or BM on days 12, 13, 18, and 19 of pregnancy. This dosing paradigm was previously used (Souza et al ., ; Piffer et al ., 2009a,b; Borges et al ., , 2017a,b) and takes into account the beginning of the critical window of male rat reproductive tract development (McIntyre et al ., ; Wilson et al ., ) and brain sexual differentiation of male fetuses (Pereira et al ., ; Pereira & Piffer, ; Piffer et al ., 2009a,b).…”

Section: Methodsmentioning

confidence: 99%

“…In recent studies, we showed that prenatal BM exposure promoted fetal reproductive reprogramming of male rat offspring, as characterized by reduction of anogenital distance, altered testicular and epididymal development, testicular morphology, impaired sperm quality, and fertility of treated animals (Borges et al ., , 2017a,b; Barros et al ., ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Prenatal exposure to betamethasone causes intergenerational impairment of epididymal development in the rat

et al. 2019

View full text Add to dashboard Cite

Background: Studies on epididymal toxicology are scarce. Betamethasone (BM) is a glucocorticoid used in clinical practice for antenatal therapy. We previously reported changes to testicular morphology, altered sperm quality, and fertility in adult rats following intrauterine administration of BM. Objectives: Given that high levels of corticosteroids during gestation lead to fetal androgen depletion, and the essential role of testosterone during epididymal development, here we investigated epididymal morphology and physiology in the F1 and F2 male offspring of female rats treated with BM during gestation. Materials and methods: Pregnant rats were randomly divided into two experimental groups: control (saline vehicle, n = 11) and BM-treated group (0.1 mg/kg betamethasone 21-phosphate disodium, n = 13). Rats received an intramuscular injection of vehicle or BM on gestational days 12, 13, 18, and 19. This encompasses the beginning of the critical window of male rat reproductive tract development. A subset of three males from each litter (n = 5 litters/group) was used: One rat per litter was euthanized at puberty, one was euthanized at adulthood, while the others were mated with a non-treated female to obtain the F2 generation. The same protocol described for the F1 was applied for F2, except for the mating protocol. Results: In both F1 and F2 generations, prenatal BM exposure resulted in delayed differentiation of the cauda epididymal epithelium, characterized by increased cribriform appearance on PND 45, and displayed weaker or non-detectable Cx43 immunostaining. Furthermore, in the F1 generation only, immunostaining of TP63, a transcription factor expressed in basal cells, appeared more intense with a greater number of TP63-positive cells observed in the cauda epididymis. In adults, the epithelial area was reduced in the F1 BM rats. The contractile activity of isolated epididymal ducts was comparable between groups. Discussion and Conclusion: Prenatal BM exposure leads to intergenerational impairment in the development and structure of the rat epididymis.

show abstract

Effects of social environments on male primate HPG and HPA axis developmental programming

Brown,

Gettler,

Rosenbaum

2024

Developmental Psychobiology

View full text Add to dashboard Cite

Developmental plasticity is particularly important for humans and other primates because of our extended period of growth and maturation, during which our phenotypes adaptively respond to environmental cues. The hypothalamus–pituitary–gonadal (HPG) and hypothalamus–pituitary–adrenal (HPA) axes are likely to be principal targets of developmental “programming” given their roles in coordinating fitness‐relevant aspects of the phenotype, including sexual development, adult reproductive and social strategies, and internal responses to the external environment. In social animals, including humans, the social environment is believed to be an important source of cues to which these axes may adaptively respond. The effects of early social environments on the HPA axis have been widely studied in humans, and to some extent, in other primates, but there are still major gaps in knowledge specifically relating to males. There has also been relatively little research examining the role that social environments play in developmental programming of the HPG axis or the HPA/HPG interface, and what does exist disproportionately focuses on females. These topics are likely understudied in males in part due to the difficulty of identifying developmental milestones in males relative to females and the general quiescence of the HPG axis prior to maturation. However, there are clear indicators that early life social environments matter for both sexes. In this review, we examine what is known about the impact of social environments on HPG and HPA axis programming during male development in humans and nonhuman primates, including the role that epigenetic mechanisms may play in this programming. We conclude by highlighting important next steps in this research area.

show abstract

Betamethasone causes intergenerational reproductive impairment in male rats

Cited by 7 publications

References 46 publications

Emerging insights into hypothalamic‐pituitary‐gonadal axis regulation and interaction with stress signalling

Emerging insights into hypothalamic‐pituitary‐gonadal axis regulation and interaction with stress signalling

Prenatal exposure to betamethasone causes intergenerational impairment of epididymal development in the rat

Effects of social environments on male primate HPG and HPA axis developmental programming

Contact Info

Product

Resources

About