The Effect of Gender-Affirming Hormone Therapy on the Risk of Subclinical Atherosclerosis in the Transgender Population: A Systematic Review.

OBJECTIVE: The impact of gender-affirming hormone therapy (GAHT) on cardiovascular (CV) health is still not entirely established. A systematic review was conducted to summarize the evidence on the risk of subclinical atherosclerosis in transgender people receiving GAHT. METHODS: A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and data were searched in PubMed, LILACS, EMBASE, and Scopus databases for cohort, case-control, and cross-sectional studies or randomized clinical trials, including transgender people receiving GAHT. Transgender men and women before and during/after GAHT for at least 2 months, compared with cisgender men and women or hormonally untreated transgender persons. Studies reporting changes in variables related to endothelial function, arterial stiffness, autonomic function, and blood markers of inflammation/coagulation associated with CV risk were included. RESULTS: From 159 potentially eligible studies initially identified, 12 were included in the systematic review (8 cross-sectional and 4 cohort studies). Studies of trans men receiving GAHT reported increased carotid thickness, brachial-ankle pulse wave velocity, and decreased vasodilation. Studies of trans women receiving GAHT reported decreased interleukin 6, plasminogen activator inhibitor-1, and tissue plasminogen activator levels and brachial-ankle pulse wave velocity, with variations in flow-mediated dilation and arterial stiffness depending on the type of treatment and route of administration. CONCLUSIONS: The results suggest that GAHT is associated with an increased risk of subclinical atherosclerosis in transgender men but may have either neutral or beneficial effects in transgender women. The evidence produced is not entirely conclusive, suggesting that additional studies are warranted in the context of primary prevention of CV disease in the transgender population receiving GAHT. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier CRD42022323757.

Fisiologia reprodutiva aplicada ao cultivo de peixes neotropicais / Reproductive physiology applied to neotropical fish rearing

A reprodução dos peixes teleósteos é regulada pela interação dos sistemas nervoso e endócrino, e essa interação é realizada pelo eixo hipotálamo-hipófise-gônadas (H-H-G). No entanto, sabe-se que os sinais ambientais (fotoperíodo, temperatura, pluviosidade entre outros fatores), são responsáveis por modular este processo. O eixo H-H-G, sintetiza e libera fatores internos (neuro-hormônios e neurotransmissores) e hormônios hipotalâmicos, hipofisários e gonadais que permitem a sincronização dos reprodutores aptos, que com condições ambientais adequadas permitem a reprodução em momento propício, com consequentemente maior sobrevivência da prole. O entendimento da fisiologia do eixo H-H-G tem sido muito importante para compreender os mecanismos regulatórios do controle neuroendócrino da reprodução em peixes teleósteos, possibilitando entender as razões do bloqueio da reprodução em cativeiro (piscicultura), ou quando a interrupção da migração reprodutiva (peixes reofílicos) por barragens é bloqueada, o que pode levar à extinção de espécies endêmicas. Esta revisão abordará o controle fisiológico do eixo H-H-G, com ênfase nas espécies neotropicais nacionais (espécies marinhas e dulciaquícolas) e discutirá as disfunções reprodutivas observadas nestes animais, quando em cativeiro. Neste contexto, a partir deste conhecimento teórico na fisiologia reprodutiva, a aplicação e/ou sugestões de tecnologias com o objetivo de obter sucesso na reprodução de espécies ameaçadas de extinção em cativeiro também serão abordados. É importante salientar que esta revisão não pretende cobrir todo o conhecimento sobre a fisiologia reprodutiva dos peixes teleósteos.

Teleost fish reproduction is regulated by the interaction of the nervous and endocrine systems, and this interaction is performed by the hypothalamic-pituitary-gonadal axis (H-H-G). However, it is known that environmental signals (photoperiod, temperature, rainfall, among other factors), are responsible to modulate this entire process. The H-H-G axis, synthesizes and releases internal factors (neurohormones and neurotransmitters) and hypothalamic, pituitary, and gonadal hormones that allow the synchronization of the able broodstocks and that, with adequate environmental conditions allow reproduction in the right time, and consequently, with a greater offspring survival. Understanding the physiology of the H-H-G axis has been important to understand the regulatory mechanisms of neuroendocrine control of reproduction in teleost fish, making it possible to understand the reasons for blocking reproduction in captivity (fish farming), or when the interruption of reproductive migration (reophilic fish) by dams is blocked, taking to the extinction of endemic species. This review will address the physiological control of the H-H-G axis, with an emphasis on National neotropical species (marine and freshwater species) and will discuss the reproductive dysfunctions observed in these animals when they are in captivity. In this context, from this theoretical knowledge about reproductive physiology, the application and/or suggestions of technologies with the objective of obtaining success in the reproduction of endangered species in captivity will also be considered. It is important to note that this review does not intend to cover all knowledge about the reproductive physiology of teleost fish.

Fisiologia reprodutiva aplicada ao cultivo de peixes neotropicais / Reproductive physiology applied to neotropical fish rearing

A reprodução dos peixes teleósteos é regulada pela interação dos sistemas nervoso e endócrino, e essa interação é realizada pelo eixo hipotálamo-hipófise-gônadas (H-H-G). No entanto, sabe-se que os sinais ambientais (fotoperíodo, temperatura, pluviosidade entre outros fatores), são responsáveis por modular este processo. O eixo H-H-G, sintetiza e libera fatores internos (neuro-hormônios e neurotransmissores) e hormônios hipotalâmicos, hipofisários e gonadais que permitem a sincronização dos reprodutores aptos, que com condições ambientais adequadas permitem a reprodução em momento propício, com consequentemente maior sobrevivência da prole. O entendimento da fisiologia do eixo H-H-G tem sido muito importante para compreender os mecanismos regulatórios do controle neuroendócrino da reprodução em peixes teleósteos, possibilitando entender as razões do bloqueio da reprodução em cativeiro (piscicultura), ou quando a interrupção da migração reprodutiva (peixes reofílicos) por barragens é bloqueada, o que pode levar à extinção de espécies endêmicas. Esta revisão abordará o controle fisiológico do eixo H-H-G, com ênfase nas espécies neotropicais nacionais (espécies marinhas e dulciaquícolas) e discutirá as disfunções reprodutivas observadas nestes animais, quando em cativeiro. Neste contexto, a partir deste conhecimento teórico na fisiologia reprodutiva, a aplicação e/ou sugestões de tecnologias com o objetivo de obter sucesso na reprodução de espécies ameaçadas de extinção em cativeiro também serão abordados. É importante salientar que esta revisão não pretende cobrir todo o conhecimento sobre a fisiologia reprodutiva dos peixes teleósteos.(AU)

Teleost fish reproduction is regulated by the interaction of the nervous and endocrine systems, and this interaction is performed by the hypothalamic-pituitary-gonadal axis (H-H-G). However, it is known that environmental signals (photoperiod, temperature, rainfall, among other factors), are responsible to modulate this entire process. The H-H-G axis, synthesizes and releases internal factors (neurohormones and neurotransmitters) and hypothalamic, pituitary, and gonadal hormones that allow the synchronization of the able broodstocks and that, with adequate environmental conditions allow reproduction in the right time, and consequently, with a greater offspring survival. Understanding the physiology of the H-H-G axis has been important to understand the regulatory mechanisms of neuroendocrine control of reproduction in teleost fish, making it possible to understand the reasons for blocking reproduction in captivity (fish farming), or when the interruption of reproductive migration (reophilic fish) by dams is blocked, taking to the extinction of endemic species. This review will address the physiological control of the H-H-G axis, with an emphasis on National neotropical species (marine and freshwater species) and will discuss the reproductive dysfunctions observed in these animals when they are in captivity. In this context, from this theoretical knowledge about reproductive physiology, the application and/or suggestions of technologies with the objective of obtaining success in the reproduction of endangered species in captivity will also be considered. It is important to note that this review does not intend to cover all knowledge about the reproductive physiology of teleost fish.(AU)

Developmental programming of the female neuroendocrine system by steroids.

Developmental programming refers to processes that occur during early life that may have long-term consequences, modulating adult health and disease. Complex diseases, such as diabetes, cancer and cardiovascular disease, have a high prevalence in different populations, are multifactorial, and may have a strong environmental component. The environment interacts with organisms, affecting their behaviour, morphology and physiology. This interaction may induce permanent or long-term changes, and organisms may be more susceptible to environmental factors during certain developmental stages, such as the prenatal and early postnatal periods. Several factors have been identified as responsible for inducing the reprogramming of various reproductive and nonreproductive tissues. Among them, both natural and synthetic steroids, such as endocrine disruptors, are known to have either detrimental or positive effects on organisms depending on the dose of exposure, stage of development and biological sexual background. The present review focuses on the action of steroids and endocrine disruptors as agents involved in developmental programming and on their modulation and effects on female neuroendocrine functions.

Leporinus elongatus induced spawning using carp pituitary extract or mammalian GnRH analogue combined with dopamine receptor antagonists

Several studies have been developed to support the replacement of the crude carp pituitary extract (CPE) by synthetic products for induced reproduction of South American rheophilic species. However, results have been quite heterogeneous and there is no consensus or a routine use of synthetic products in these species. Thus, the aim of this study was to evaluate the ovulatory process in L. elongatus using different protocols of hormonal induction. Thus, fifteen wild mature females maintained at the Experimental Fish Station, Salto Grande, SP, Brazil were submitted to three different hormonal treatments: CPE (fractioned dose: 0.5 and 5.0 mg kg-1 ); mGnRHa (single dose: 3.5 µg kg-1 ) and mGnRHa (single dose: 5.0 µg kg-1 ). The spawning rate and absolute fecundity were similar among the treatments, but fertility rates were higher for CPE treatment (23.60 ± 9.40) then for mGnRHa treatments (close to or zero zero). Although females ovulated in all treatments, none of them provided viable embryos, showing hatching rates close to zero or zero. Both mGnRHa treatments were more potent for inducing the ovulatory process then CPE treatment, which was evidenced by the fact that the formers showed higher volume density of postovulatory follicles (POF). Accordingly, E2 and 17α-OHP plasma levels were higher for the mGnRHa treated females compared to the CPE one at the time of ovulation. In this study we confirmed previous scientific evidence that, regardless of whether promoting ovulation, the use of conventional CPE and GnRH doses are not appropriate for some South American migratory species, due to the nonattainment of viable embryos. Moreover, we have brought new information about the relationship between reproductive performance and gonadal steroids concentrations using different hormonal therapies, contributing to understand the reasons for Leporinus elongatus embryo loss in induced spawning.

Leporinus elongatus induced spawning using carp pituitary extract or mammalian GnRH analogue combined with dopamine receptor antagonists

Several studies have been developed to support the replacement of the crude carp pituitary extract (CPE) by synthetic products for induced reproduction of South American rheophilic species. However, results have been quite heterogeneous and there is no consensus or a routine use of synthetic products in these species. Thus, the aim of this study was to evaluate the ovulatory process in L. elongatus using different protocols of hormonal induction. Thus, fifteen wild mature females maintained at the Experimental Fish Station, Salto Grande, SP, Brazil were submitted to three different hormonal treatments: CPE (fractioned dose: 0.5 and 5.0 mg kg-1 ); mGnRHa (single dose: 3.5 µg kg-1 ) and mGnRHa (single dose: 5.0 µg kg-1 ). The spawning rate and absolute fecundity were similar among the treatments, but fertility rates were higher for CPE treatment (23.60 ± 9.40) then for mGnRHa treatments (close to or zero zero). Although females ovulated in all treatments, none of them provided viable embryos, showing hatching rates close to zero or zero. Both mGnRHa treatments were more potent for inducing the ovulatory process then CPE treatment, which was evidenced by the fact that the formers showed higher volume density of postovulatory follicles (POF). Accordingly, E2 and 17α-OHP plasma levels were higher for the mGnRHa treated females compared to the CPE one at the time of ovulation. In this study we confirmed previous scientific evidence that, regardless of whether promoting ovulation, the use of conventional CPE and GnRH doses are not appropriate for some South American migratory species, due to the nonattainment of viable embryos. Moreover, we have brought new information about the relationship between reproductive performance and gonadal steroids concentrations using different hormonal therapies, contributing to understand the reasons for Leporinus elongatus embryo loss in induced spawning.(AU)

Leporinus elongatus induced spawning using carp pituitary extract or mammalian GnRH analogue combined with dopamine receptor antagonists.

Several studies have been developed to support the replacement of the crude carp pituitary extract (CPE) by synthetic products for induced reproduction of South American rheophilic species. However, results have been quite heterogeneous and there is no consensus or a routine use of synthetic products in these species. Thus, the aim of this study was to evaluate the ovulatory process in L. elongatus using different protocols of hormonal induction. Thus, fifteen wild mature females maintained at the Experimental Fish Station, Salto Grande, SP, Brazil were submitted to three different hormonal treatments: CPE (fractioned dose: 0.5 and 5.0 mg kg-1); mGnRHa (single dose: 3.5 µg kg-1) and mGnRHa (single dose: 5.0 µg kg-1). The spawning rate and absolute fecundity were similar among the treatments, but fertility rates were higher for CPE treatment (23.60 ± 9.40) then for mGnRHa treatments (close to or zero zero). Although females ovulated in all treatments, none of them provided viable embryos, showing hatching rates close to zero or zero. Both mGnRHa treatments were more potent for inducing the ovulatory process then CPE treatment, which was evidenced by the fact that the formers showed higher volume density of postovulatory follicles (POF). Accordingly, E2 and 17α-OHP plasma levels were higher for the mGnRHa treated females compared to the CPE one at the time of ovulation. In this study we confirmed previous scientific evidence that, regardless of whether promoting ovulation, the use of conventional CPE and GnRH doses are not appropriate for some South American migratory species, due to the non-attainment of viable embryos. Moreover, we have brought new information about the relationship between reproductive performance and gonadal steroids concentrations using different hormonal therapies, contributing to understand the reasons for Leporinus elongatus embryo loss in induced spawning.

Endocrine disruption of phenanthrene in the protogynous dusky grouper Epinephelus marginatus (Serranidae: Perciformes).

The dusky grouper Epinephelus marginatus is a protogynous hermaphrodite fish, that maintains high levels of plasma steroids as juveniles, as substrates for sex inversion. These fish are exposed to marine pollution from oil spills during cargo handling. Polycyclic aromatic hydrocarbons (PAHs), such as phenanthrene (Phe), are the main crude oil components and are toxic to fish, acting as endocrine disruptors (ED). This is the first study that investigated impacts of Phe as an ED in E. marginatus juveniles. An in vivo sublethal exposure (96h) to Phe was carried out at two concentrations (0.1mg/L and 1mg/L); exposure to the vehicle (ethanol; ETOH) was also performed. Plasma levels of 17ß-estradiol (E2), testosterone (T) and 11-ketotestosterone (11-KT) were measured by ELISA. Gonads, liver and spleen were processed for histological analysis. In an in vitro bioassay, gonad fragments were incubated with Phe (8.91mg/L) or ETOH. Steroid levels in the culture media were measured by ELISA. The in vivo exposure to Phe triggered an increase of the area of the hepatocytes, increased number of melanomacrophagic centers and hemosiderosis in the spleen; ETOH induced similar effects on spleen. E2 and T levels did not change in plasma or in vitro media. In plasma, ETOH decreased 11-KT levels. Phenanthrene sharply reduced 11-KT levels in vitro. Although in vivo bioassay results were not unequivocal owing to ethanol effects, Phe might disrupt steroidogenesis in juvenile grouper, possibly causing dysfunctions during sex change and gonadal maturity, considering the importance of 11-KT in developing ovaries.

Controle neuroendócrino da ovogênese em peixes teleósteos / Neuroendocrine control of oogenesis in teleost fish

O estudo sobre o controle neuroendócrino da reprodução em teleósteos tem sido importante paracompreender os mecanismos regulatórios da atividade reprodutiva destes animais e possibilitado entender asrazões do bloqueio da reprodução no cativeiro. A reprodução em peixes é modulada por fatores ambientais econtrolada endogenamente por um sistema neuroendócrino, principalmente pelo eixo hipotálamo-hipófisegônadas(H-H-G). Este eixo coordena a síntese de hormônios liberadores, inibidores, gonadotropinas, esteroidesgonadais, regulando assim a reprodução. Este controle endócrino se altera quando espécies migradoras sãotransferidas para o cativeiro, pois neste ambiente confinado, algumas espécies não conseguem eliminar os seusgametas. Neste caso, intervenções hormonais exógenas em diferentes níveis do eixo H-H-G são necessárias paradar continuidade ao processo de maturação gonadal. Esta revisão aborda a fisiologia do eixo H-H-G, com ênfasenos estudos realizados nas espécies neotropicais nacionais e discute disfunções decorrentes do bloqueio dareprodução em animais em cativeiro.

The study on the neuroendocrine control of teleost reproduction has been important to understand theregulatory mechanisms of reproductive activity of these animals, allowing the understanding the reasons ofreproduction impairment when they are under captivity conditions. The reproduction in fish is modulated byenvironmental factors and endogenously controlled by a neuroendocrine system, mainly by the hypothalamicpituitary-gonadsaxis (H-P-G). This axis coordinates the synthesis of releasing and inhibitory hormones,gonadotropins, gonadal steroids, controlling therefore reproduction. The endocrine control is altered whenmigratory species are transferred to captivity, where some species cannot release their gametes. In this case,exogenous hormones interventions at different levels of the H-P-G axis are necessary to continue the gonadalmaturation process. This review addresses the physiology of the H-P-G axis, emphasizing the studies with thenational neotropical species and discusses dysfunctions resulting from reproduction impairment in captivity.

Controle neuroendócrino da ovogênese em peixes teleósteos / Neuroendocrine control of oogenesis in teleost fish

O estudo sobre o controle neuroendócrino da reprodução em teleósteos tem sido importante paracompreender os mecanismos regulatórios da atividade reprodutiva destes animais e possibilitado entender asrazões do bloqueio da reprodução no cativeiro. A reprodução em peixes é modulada por fatores ambientais econtrolada endogenamente por um sistema neuroendócrino, principalmente pelo eixo hipotálamo-hipófisegônadas(H-H-G). Este eixo coordena a síntese de hormônios liberadores, inibidores, gonadotropinas, esteroidesgonadais, regulando assim a reprodução. Este controle endócrino se altera quando espécies migradoras sãotransferidas para o cativeiro, pois neste ambiente confinado, algumas espécies não conseguem eliminar os seusgametas. Neste caso, intervenções hormonais exógenas em diferentes níveis do eixo H-H-G são necessárias paradar continuidade ao processo de maturação gonadal. Esta revisão aborda a fisiologia do eixo H-H-G, com ênfasenos estudos realizados nas espécies neotropicais nacionais e discute disfunções decorrentes do bloqueio dareprodução em animais em cativeiro.(AU)

The study on the neuroendocrine control of teleost reproduction has been important to understand theregulatory mechanisms of reproductive activity of these animals, allowing the understanding the reasons ofreproduction impairment when they are under captivity conditions. The reproduction in fish is modulated byenvironmental factors and endogenously controlled by a neuroendocrine system, mainly by the hypothalamicpituitary-gonadsaxis (H-P-G). This axis coordinates the synthesis of releasing and inhibitory hormones,gonadotropins, gonadal steroids, controlling therefore reproduction. The endocrine control is altered whenmigratory species are transferred to captivity, where some species cannot release their gametes. In this case,exogenous hormones interventions at different levels of the H-P-G axis are necessary to continue the gonadalmaturation process. This review addresses the physiology of the H-P-G axis, emphasizing the studies with thenational neotropical species and discusses dysfunctions resulting from reproduction impairment in captivity.(AU)

The Receptive Endometrial Transcriptomic Signature Indicates an Earlier Shift from Proliferation to Metabolism at Early Diestrus in the Cow.

This study aimed to characterize the endometrial transcriptome and functional pathways overrepresented in the endometrium of cows treated to ovulate larger (≥13 mm) versus smaller (≤12 mm) follicles. Nelore cows were presynchronized prior to receiving cloprostenol (large follicle [LF] group) or not (small follicle [SF] group), along with a progesterone (P4) device on Day (D) -10. Devices were withdrawn and cloprostenol administered 42-60 h (LF) or 30-36 h (SF) before GnRH agonist treatment (D0). Tissues were collected on D4 (experiment [Exp.] 1; n = 24) or D7 (Exp. 2; n = 60). Endometrial transcriptome was obtained by RNA-Seq, whereas proliferation and apoptosis were assessed by immunohistochemistry. Overall, LF cows developed larger follicles and corpora lutea, and produced greater amounts of estradiol (D-1, Exp. 1, SF: 0.7 ± 0.2; LF: 2.4 ± 0.2 pg/ml; D-1, Exp. 2, SF: 0.5 ± 0.1; LF: 2.3 ± 0.6 pg/ml) and P4 (D4, Exp. 1, SF: 0.8 ± 0.1; LF: 1.4 ± 0.2 ng/ml; D7, Exp. 2, SF: 2.5 ± 0.4; LF: 3.7 ± 0.4 ng/ml). Functional enrichment indicated that biosynthetic and metabolic processes were enriched in LF endometrium, whereas SF endometrium transcriptome was biased toward cell proliferation. Data also suggested reorganization of the extracellular matrix toward a proliferation-permissive phenotype in SF endometrium. LF endometrium showed an earlier onset of proliferative activity, whereas SF endometrium expressed a delayed increase in glandular epithelium proliferation. In conclusion, the periovulatory endocrine milieu regulates bovine endometrial transcriptome and seems to determine the transition from a proliferation-permissive to a biosynthetic and metabolically active endometrial phenotype, which may be associated with the preparation of an optimally receptive uterine environment.

Metabolic and endocrine changes during the reproductive cycle of dermatophagic caecilians in captivity.

The amphibian order Gymnophiona is poorly known, and studies about their reproduction are mainly comparative and descriptive, focusing on the structure of testes, ovaries and oviducts. However, to understand the reproductive processes, including those of the oviparous dermatophagic species, it is important to know the dynamics of storage and mobilization of energetic substrates to gonads and skin during the reproductive cycle of males and females, as well as the endocrine control associated. For the present study, total lipids and proteins were measured during the annual cycle in the plasma, liver, muscle, testes, ovaries and skin of Siphonops annulatus in captivity. Plasma levels of gonadal steroids (estradiol, testosterone and progesterone) were quantified by radioimmunoassay. Histological analyses of ovaries and testes were performed to classify the maturation stages of the animals during the reproductive cycle. Gonadal maturation in males and females of S. annulatus was accompanied by metabolic changes in reserve tissues, which supported gonadal development and prepared the females' epidermis for skin feeding by the offspring. Even in confinement conditions, females and males synchronized the reproductive period. However, due to the absence of environmental cues in captivity inadequate levels of the hormones responsible for gamete release were triggered, leading to a lack of reproductive success.

Involvement of pituitary gonadotropins, gonadal steroids and breeding season in sex change of protogynous dusky grouper, Epinephelus marginatus (Teleostei: Serranidae), induced by a non-steroidal aromatase inhibitor.

Two experiments were performed using the aromatase inhibitor (AI) letrozole (100mg/kg) to promote sex change, from female-to-male, in protogynous dusky grouper. One experiment was performed during the breeding season (spring) and the other at the end of the breeding season (summer). During the spring, AI promoted sex change after 9 weeks and the sperm produced was able to fertilize grouper oocytes. During the summer, the sex change was incomplete; intersex individuals were present and sperm was not released by any of the animals. Sex changed gonads had a lamellar architecture; cysts of spermatocytes and spermatozoa in the lumen of the germinal compartment. In the spring, after 4 weeks, 11ketotestosterone (11KT) levels were higher in the AI than in control fish, and after 9 weeks, coincident with semen release, testosterone levels increased in the AI group, while 11KT returned to the initial levels. Estradiol (E2) levels remained unchanged during the experimental period. Instead of decreasing throughout the period, as in control group, 17 α-OH progesterone levels did not change in the AI-treated fish, resulting in higher values after 9 weeks when compared with control fish. fshß and lhß gene expression in the AI animals were lower compared with control fish after 9 weeks. The use of AI was effective to obtain functional males during the breeding season. The increase in androgens, modulated by gonadotropins, triggered the sex change, enabling the development of male germ cells, whereas a decrease in E2 levels was not required to change sex in dusky grouper.