Intervenções psicológicas necessárias: a prática como residente no serviço de medicina fetal / Necessary psychological interventions: the practice as a resident in the fetal medicine service / Intervenciones psicológicas necesarias: la práctica como residente en el servicio de medicina fetal

Com os avanços tecnológicos e o aprimoramento da prática médica via ultrassonografia, já é possível detectar possíveis problemas no feto desde a gestação. O objetivo deste estudo foi analisar a prática do psicólogo no contexto de gestações que envolvem riscos fetais. Trata-se de um estudo qualitativo sob formato de relato de experiência como psicólogo residente no Serviço de Medicina Fetal da Maternidade Escola da Universidade Federal do Rio de Janeiro (UFRJ). Os registros, feitos por observação participante e diário de campo, foram analisados em dois eixos temáticos: 1) intervenções psicológicas no trabalho em equipe em consulta de pré-natal, exame de ultrassonografia e procedimento de amniocentese; e 2) intervenções psicológicas em casos de bebês incompatíveis com a vida. Os resultados indicaram que o psicólogo nesse serviço é essencial para atuar de forma multiprofissional na assistência pré-natal para gravidezes de alto risco fetal. Ademais, a preceptoria do residente é relevante para sua formação e treinamento para atuação profissional no campo da psicologia perinatal.(AU)

Face to the technological advances and the improvement of medical practice via ultrasound, it is already possible to detect possible problems in the fetus since pregnancy. The objective of this study was to analyze the psychologist's practice in the context of pregnancies which involve fetal risks. It is a qualitative study based on an experience report as a psychologist trainee at the Fetal Medicine Service of the Maternity School of UFRJ. The records, based on the participant observation and field diary, were analyzed in two thematic axes: 1) psychological interventions in the teamwork in the prenatal attendance, ultrasound examination and amniocentesis procedure; and 2) psychological interventions in cases of babies incompatible to the life. The results indicated that the psychologist in this service is essential to work in a multidisciplinary way at the prenatal care for high fetal risk pregnancies. Furthermore, the resident's preceptorship is relevant to their education and training for professional performance in the field of Perinatal Psychology.(AU)

Con los avances tecnológicos y la mejora de la práctica médica a través de la ecografía, ya se puede detectar posibles problemas en el feto desde el embarazo. El objetivo de este estudio fue analizar la práctica del psicólogo en el contexto de embarazos de riesgos fetal. Es un estudio cualitativo basado en un relato de experiencia como residente de psicología en el Servicio de Medicina Fetal de la Escuela de Maternidad de la Universidade Federal do Rio de Janeiro (UFRJ). Los registros, realizados en la observación participante y el diario de campo, se analizaron en dos ejes temáticos: 1) intervenciones psicológicas en el trabajo en equipo, en la consulta prenatal, ecografía y los procedimientos de amniocentesis; y 2) intervenciones psicológicas en casos de bebés incompatibles con la vida. Los resultados señalaron como fundamental la presencia del psicólogo en este servicio trabajando de forma multidisciplinar en la atención prenatal en el contexto de embarazos de alto riesgo fetal. Además, la tutela del residente es relevante para su educación y formación para el desempeño profesional en el campo de la Psicología Perinatal.(AU)

Percepções e expectativas de homens trans acerca dos relacionamentos afetivo-sexuais pós-transição / Trans men's perceptions and expectations of post-transition affective-sexual relationships / Percepciones y expectativas de los hombres trans sobre las relaciones afectivo-sexuales después de la transición

As identidades transmasculinas ganharam visibilidade social e acadêmica no Brasil a partir de 2010, contudo, as questões subjetivas dos homens trans ainda são pouco debatidas, em particular temas associados aos relacionamentos afetivos na experiência desses sujeitos. Este estudo qualitativo tem por objetivo identificar as percepções e expectativas dos homens trans acerca dos relacionamentos afetivo-sexuais no cenário pós-transição de gênero. Participaram da pesquisa 15 homens transexuais hormonizados, com idades entre 20 e 41 anos. A coleta de dados foi realizada por meio de entrevista semiestruturada nas modalidades presencial e on-line. Empregou-se análise temática reflexiva, que resultou em dois temas analíticos. Os resultados apontam que os homens trans, ao contrário de suas expectativas iniciais, percebem que tiveram menos oportunidades de relacionamentos afetivo-sexuais depois de sua transição de gênero. Os participantes atribuem essa dificuldade especialmente ao fato de não terem se submetido à cirurgia de redesignação sexual. O desconforto é acentuado por sua materialidade corpórea divergente da cisnormatividade, sistema regulador que associa pessoas pertencentes ao gênero masculino à presença de um pênis. Outra fonte de desconforto é o repúdio social, que alimenta a abjeção, exotização e fetichização dos corpos transmasculinos. Também são descritas as especificidades do relacionamento dos homens trans com mulheres cisgênero, heterossexuais e lésbicas. Os resultados evidenciam que a fixação persistente no genital, como referente e signo determinante do gênero e da sexualidade, modula e regula a busca e o encontro de parceira(o) íntima(o).(AU)

Transmasculine identities have gained social and academic visibility in Brazil since 2010, but subjective issues, especially those associated with affective relationships, are still little discussed. This qualitative study sought to identify trans men's perceptions and expectations regarding post-transition affective-sexual relationships. A total of 15 transsexual men undergoing hormone therapy, aged between 20 and 41 years, participated in the research. Data were collected by means of in-person and online semi-structured interviews and analysed using reflexive thematic analysis, which resulted in two analytical themes. Results show that trans men, differently from their initial expectations, perceive fewer opportunities for affective-sexual relationships after their gender transition. The participants attribute this difficulty, especially, to the fact that they have not undergone sexual reassignment surgery. Discomfort isaccentuated by their bodily materiality diverging from cisnormativity, the regulatory system that associates people belonging to the male gender with the presence of a penis. Another source of discomfort is the social repudiation, which reinforces the abjection, exoticization, and fetishization of transmasculine bodies. The specifics of trans men's relationships with cisgender, heterosexual, and lesbian women are also described. The results show that the persistent fixation on the genital, as a referent and determinant sign of gender and sexuality, modulates and regulates the search for and encounter of intimate partners.(AU)

Las identidades transmasculinas han ganado visibilidad social y académica en Brasil desde 2010, sin embargo, las cuestiones subjetivas de los hombres trans son aún poco discutidas, en particular las cuestiones asociadas a las relaciones afectivas en la experiencia de estos sujetos. Este estudio cualitativo tiene como objetivo identificar las percepciones y expectativas de los hombres trans sobre las relaciones afectivo-sexuales después de la transición de género. Participaron en la investigación 15 hombres transexuales hormonados, de edades comprendidas entre los 20 y los 41 años. La recopilación de datos se realizó mediante una entrevista semiestructurada en las modalidades presencial y en línea. Se realizó un análisis temático reflexivo, que dio como resultado dos temas analíticos. Los resultados muestran que los hombres trans, al contrario de sus expectativas iniciales, perciben que han tenido menos oportunidades de relaciones afectivo-sexuales después de su transición de género. Los participantes atribuyen esta dificultad especialmente al hecho de no haberse sometido a cirugía de reasignación sexual. La incomodidad se acentúa por su materialidad corpórea divergente de la cisnormatividad, un sistema normativo según el cual las personas pertenecientes al género masculino deben tener pene. Otra fuente de malestar es el repudio social, que alimenta la abyección, la exotización y la fetichización de los cuerpos transmasculinos. También se describen las especificidades de las relaciones de los hombres trans con las mujeres heterosexuales, cisgénero y lesbianas. Los resultados muestran que la persistente fijación en los genitales, como referente y signo determinante del género y la sexualidad, modula y regula la búsqueda y el encuentro de parejas íntimas.(AU)

Percepção sobre o cuidado à perda gestacional: estudo qualitativo com casais brasileiros / Perceptions on pregnancy loss care: a qualitative study with brazilian couples / Percepción sobre la atención a la pérdida del embarazo: estudio cualitativo con parejas brasileñas

Este artigo analisou a percepção e os sentimentos de casais sobre o atendimento recebido nos serviços de saúde acessados em função de perda gestacional (óbito fetal ante e intraparto). O convite para a pesquisa foi divulgado em mídias sociais (Instagram e Facebook). Dos 66 casais que contataram a equipe, 12 participaram do estudo, cuja coleta de dados ocorreu em 2018. Os casais responderam conjuntamente a uma ficha de dados sociodemográficos e uma entrevista semiestruturada, realizada presencialmente (n=4) ou por videochamada (n=8). Os dados foram gravados em áudio e posteriormente transcritos. A Análise Temática indutiva das entrevistas identificou cinco temas: sentimento de impotência, iatrogenia vivida nos serviços, falta de cuidado em saúde mental, não reconhecimento da perda como evento com consequências emocionais negativas, e características do bom atendimento. Os achados demonstraram situações de violência, comunicação deficitária, desvalorização das perdas precoces, falta de suporte para contato com o bebê falecido e rotinas pouco humanizadas, especialmente durante a internação após a perda. Para aprimorar a assistência às famílias enlutadas, sugere-se qualificação profissional, ampliação da visibilidade do tema entre diferentes atores e reorganização dos serviços, considerando uma diretriz clínica para atenção ao luto perinatal, com destaque para o fortalecimento da inserção de equipes de saúde mental no contexto hospitalar.(AU)

This study analyzed couples' perceptions and feelings about pregnancy loss care (ante and intrapartum fetal death). A research invitation was published on social media (Instagram and Facebook) and data collection took place in 2018. Of the 66 couples who contacted the research team, 12 participated in the study by filling a sociodemographic questionnaire and answering a semi-structured interview in person (n=04) or by video call (n=08). All interviews were audio recorded, transcribed, and examined by Inductive Thematic Analysis, which identified five themes: feelings of impotence, iatrogenic experiences in health services, lack of mental health care, not recognizing pregnancy loss as an emotionally overwhelming event, and aspects of good healthcare. Analysis showed experiences of violence, poor communication, devaluation of early losses, lack of support for contact with the deceased baby, and dehumanizing routines, especially during hospitalization after loss. Professional qualification, extended pregnancy loss visibility among different stakeholders, and reorganization of health services are needed to improve the care offered to grieving families, considering a clinical guideline for perinatal grief care with emphasis on strengthening the insertion of mental health teams in the hospital context.(AU)

Este estudio analizó las percepciones y sentimientos de parejas sobre la atención recibida en los servicios de salud a los que accedieron debido a la pérdida del embarazo (muerte fetal ante e intraparto). La invitación al estudio se publicó en las redes sociales (Instagram y Facebook). De las 66 parejas que se contactaron con el equipo, 12 participaron en el estudio, cuya recolección de datos se realizó en 2018. Las parejas respondieron un formulario de datos sociodemográficos y realizaron una entrevista semiestructurada presencialmente (n=4) o por videollamada (n=08). Los datos se grabaron en audio para su posterior transcripción. El análisis temático inductivo identificó cinco temas: Sentimiento de impotencia, experiencias iatrogénicas en los servicios, falta de atención a la salud mental, falta de reconocimiento de la pérdida como un evento con consecuencias emocionales negativas y características de buena atención. Los hallazgos evidenciaron situaciones de violencia, comunicación deficiente, desvalorización de las pérdidas tempranas, falta de apoyo para el contacto con el bebé fallecido y rutinas poco humanizadas, especialmente durante la hospitalización tras la pérdida. Para mejorar la atención a las familias en duelo, se sugiere capacitación profesional, ampliación de la visibilidad del tema entre los diferentes actores y reorganización de los servicios, teniendo en cuenta una guía clínica para la atención del duelo perinatal, enfocada en fortalecer la inserción de los equipos de salud mental en el contexto hospitalario.(AU)

Hypomorphism of a Novel Long ERα Isoform Causes Severe Reproductive Dysfunctions in Female Mice.

Estrogen receptor alpha (ERα)-mediated estrogen signaling plays a pivotal role in both reproductive and nonreproductive functions. Transcriptional regulation of the ERα gene is highly complex, with multiple transcript variants being differentially produced across the tissues. However, tissue-specific variation and physiological specificity of the ERα variants are not yet fully understood. In an attempt to generate a Cre-dependently restorable ERα-null mouse for functional genetic studies, we unexpectedly produced ERα hypomorphic mice with biased downregulation of a previously unappreciated long ERα isoform that is enriched in the female reproductive organs (uterus and ovaries) and the pituitary but minimally expressed in the brain. Female homozygous mutant mice were capable of pregnancy but displayed irregular estrus cycle and rarely kept newborn pups alive. No significant morphological and pathological changes in reproductive system or disruption of body weight homeostasis were seen in female homozygous mutant mice. Collectively, our results define a tissue-specific enriched long ERα isoform and its preferential role in female reproductive function rather than body weight homeostasis.

Parto domiciliar planejado assistido por enfermeira obstétrica: significados, experiências e motivação para essa escolha / Parto domiciliario planificado asistido por enfermera obstétrica: significados, experiencias y motivación para esta elección / Planned home birth assisted by a midwife nurse: meanings, experiences and motivation for this choice

RESUMO Objetivo: compreender os significados e experiências de mulheres que vivenciaram o parto domiciliar planejado assistido por enfermeira obstétrica e a motivação (das mulheres) para essa escolha. Metodologia: estudo qualitativo, exploratório e descritivo, com 16 mulheres, realizado por meio de entrevista semiestruturada e analisado pelos pressupostos da análise temática de conteúdo. Resultados: as mulheres vivenciaram o parto com tranquilidade, autonomia e respeito, escolheram as posições e as pessoas de sua preferência. O parto teve significado de vitória e de libertação, cuja experiência foi descrita como inesquecível, fantástica, intensa e protagonizada pela mulher. O descontentamento com o modelo de assistência vigente, a participação em grupo de gestantes, o acesso a informações e a vivência de violência obstétrica anterior motivaram as mulheres a optarem pelo parto domiciliar. Considerações finais: as experiências das mulheres convergem para o exercício da autonomia e respeito à individualidade. Evidencia-se o protagonismo das mulheres que vivenciaram um parto natural e livre de intervenções. A assistência obstétrica foi centrada nas necessidades da parturiente, proporcionou confiança, segurança, tranquilidade e respeito às suas escolhas. Aponta-se a necessidade de ampliar a assistência ao parto por enfermeiras obstétricas às mulheres que desejam o parto domiciliar planejado. Políticas públicas de assistência ao parto podem viabilizar isso.

RESUMEN Objetivo: comprender los significados y las experiencias de las mujeres que vivieron el parto domiciliario planificado asistido por enfermera obstétrica y la motivación (de las mujeres) para esta elección. Metodología: estudio cualitativo, exploratorio y descriptivo, con 16 mujeres, realizado a través de entrevista semiestructurada y analizado por los supuestos del análisis de contenido temático. Resultados: las mujeres experimentaron el parto con tranquilidad, autonomía y respeto, eligieron las posiciones y las personas de su preferencia. El parto tuvo un significado de victoria y liberación, cuya experiencia se describió como inolvidable, fantástica, intensa y protagonizada por la mujer. La insatisfacción con el modelo de atención actual, la participación en grupo de mujeres embarazadas, el acceso a informaciones y la experiencia de violencia obstétrica anterior motivaron a las mujeres a optar por el parto domiciliario. Consideraciones finales: las experiencias de las mujeres convergen para el ejercicio de la autonomía y respeto a la individualidad. Se evidencia el protagonismo de las mujeres que experimentaron un parto natural y libre de intervenciones. La atención obstétrica se centró en las necesidades de la parturienta, proporcionó confianza, seguridad, tranquilidad y respeto con sus elecciones. Se señala la necesidad de ampliar la atención al parto por enfermeras obstétricas a las mujeres que desean el parto domiciliario planificado. Las políticas públicas de atención al parto pueden hacer esto posible.

ABSTRACT Objective: to understand the meanings and experiences of women who dealt with planned home birth assisted by a nurse midwife and the motivation (of these women) for this choice. Methodology: qualitative, exploratory and descriptive study, with 16 women, performed by means of semi-structured interviews and analyzed by the assumptions of thematic content analysis. Results: the women experienced childbirth with tranquility, autonomy and respect, and they chose the positions and people of their preference. Childbirth had a meaning of victory and liberation, whose experience was described as unforgettable, fantastic, intense and carried out by the woman. The dissatisfaction with the current model of care, the participation in a group for pregnant women, the access to information and the experience of previous obstetric violence motivated women to choose home birth. Final considerations: the women's experiences converge towards the exercise of autonomy and respect for individuality. The leading role of women who experienced a natural birth and free of interventions, should be highlighted. Obstetric care was focused on the parturient woman's needs, provided confidence, security, tranquility and respect for her choices. There is a need to expand childbirth care provided by nurse midwives to women who wish to have a planned home birth. Public policies for childbirth care can make this possible.

Circadian effects of ionizing radiation on reproductive function and clock genes expression in male mouse.

BACKGROUND: Exposure to the ionizing radiation (IR) encountered outside the magnetic field of the Earth poses a persistent threat to the reproductive functions of astronauts. The potential effects of space IR on the circadian rhythms of male reproductive functions have not been well characterized so far. METHODS: Here, we investigated the circadian effects of IR exposure (3 Gy X-rays) on reproductive functional markers in mouse testicular tissue and epididymis at regular intervals over a 24-h day. For each animal, epididymis was tested for sperm motility, and the testis tissue was used for daily sperm production (DSP), testosterone levels, and activities of testicular enzymes (glucose-6-phosphate dehydrogenase (G6PDH), sorbitol dehydrogenase (SDH), lactic dehydrogenase (LDH), and acid phosphatase (ACP)), and the clock genes mRNA expression such as Clock, Bmal1, Ror-α, Ror-ß, or Ror-γ. RESULTS: Mice exposed to IR exhibited a disruption in circadian rhythms of reproductive markers, as indicated by decreased sperm motility, increased daily sperm production (DSP), and reduced activities of testis enzymes such as G6PDH, SDH, LDH, and ACP. Moreover, IR exposure also decreased mRNA expression of five clock genes (Clock, Bmal1, Ror-α, Ror-ß, or Ror-γ) in testis, with alteration in the rhythm parameters. CONCLUSION: These findings suggested potential health effects of IR exposure on reproductive functions of male astronauts, in terms of both the daily overall level as well as the circadian rhythmicity.

Clinical Potential of Kisspeptin in Reproductive Health.

Kisspeptins are a family of hypothalamic neuropeptides that are essential for the regulation of reproductive physiology. Their importance in reproductive health became apparent in 2003, when loss-of-function variants in the gene encoding the kisspeptin receptor were reported to result in isolated congenital hypogonadotropic hypogonadism (CHH). It has since been ascertained that hypothalamic kisspeptin neurons regulate gonadotropin-releasing hormone (GnRH) secretion to thus stimulate the remainder of the reproductive endocrine axis. In this review, we discuss genetic variants that affect kisspeptin receptor signaling, summarize data on KISS1R agonists, and posit possible clinical uses of native and synthetic kisspeptin receptor agonists for the investigation and treatment of reproductive disorders.

Correlação entre sexo, idade e estado reprodutivo com o comportamento canino avaliado pela ferramenta C-BARQ / Correlation between gender, age and reproductive status with canine behavior assessed by the C-BARQ tool

Este estudo objetivou avaliar o comportamento de cães de responsáveis brasileiros, através do Canine Behavioral Assessment and Research Questionnaire (C-BARQ) e estabelecer se estes comportamentos apresentam relação significativa com a idade, sexo e castração do animal. O questionário foi respondido pelos participantes entre novembro de 2018 a abril de 2020. As amostras foram divididas de acordo com o sexo (fêmeas ou machos), a idade (um ano ou menos, de um a três anos, de três a sete anos, de sete a dez anos ou mais de dez anos) e o status reprodutivo do animal (castrados ou inteiros). Para cada questionário respondido, foram calculados os escores das 14 categorias de comportamento investigados pelo C-BARQ e, através do programa Biostat 5.3, utilizou-se o coeficiente de correlação de Spearman com nível de significância de 5% para avaliar a correlação entre estes escores com os fatores idade, sexo e status reprodutivo dos animais. Os resultados sugerem maiores escores de comportamentos agressivos em cães mais velhos e em cães castrados. A castração também obteve associação com maiores escores de medo de outros cães. Os achados evidenciam necessidade de estudos que busquem investigar de que modo a castração se vincula com estes comportamentos que podem comprometer a convivência entre o responsável e seu cão.

This study investigated Brazilian’s dogs behavior through the Canine Behavioral Assessment and Research Questionnaire (C-BARQ) and establish if these behaviors have a significant relationship with the age, sex and neutering status of the animal. The questionnaire was answered by owners between November 2018 and April 2020. The sample was divided according to sex (female or male), age (one year or less, from one to three years, from three to seven years, from seven to ten years or more than ten years) and the reproductive status of the animal (neutered or not). For each questionnaire answered, the scores of the 14 behavior categories investigated by C-BARQ were calculated and Spearman’s correlation coefficient with a significance level of 5% was used to assess the correlation between these scores with the factors age, sex and reproductive status of the animals (Biostat 5.3 program). The results suggest higher scores for aggressive behavior in older dogs and in neutered dogs. Neutering was also associated with higher scores of fear from other dogs. The findings suggest the need for studies that seek to investigate how castration is linked to these behaviors that can deteriorate the owner-dog relationship.

State of assisted reproduction technology in the coronavirus disease 2019 era and consequences on human reproductive system.

The outbreak of the coronavirus disease 2019 (COVID-19) has created havoc on the socio-economic aspect of the world. With billions of lives being affected by this wrecking pandemic, global fertility services were also not left untouched by its impact. The possibility of sexual transmission of SARS-CoV-2 virus, its impact on male and female fertility, pregnancy, its potential teratogenic effect, and handling of gametes in the clinical laboratories were major concerns among reproductive medicine specialists, which led down all the reproductive health services, including IUI, IVF/ICSI in most of the countries. Even the people did not intend to conceive during the pandemic crisis and were hesitant to avail such services. Discrete evidence regarding the pathophysiology of COVID-19 infection and its impact on the human reproductive system is not very clear. In this review article, we intend to incorporate all the evidence related to the COVID-19 infection and its impact on human reproduction available to date. It is our responsibility to provide rightful information and to keep our patients familiar with the existing lack of clear evidence. In this COVID-19 era, it is important that the fertility management be prioritized in sub-fertile couples with diminished fertility reserve and high-risk conditions, like malignancies, that may affect their long-term fertility prospects.

Reproductive and metabolic adaptation to multistressor training in women.

Hypothalamic-pituitary-gonadal (HPG) axis suppression in exercising women can be caused by low energy availability (EA), but the impact of a real-world, multistressor training environment on reproductive and metabolic function is unknown. This study aimed to characterize reproductive and metabolic adaptation in women undertaking basic military training. A prospective cohort study in women undertaking 11-month initial military training (n = 47) was carried out. Dynamic low-dose 1-h gonadotrophin-releasing hormone (GnRH) tests were completed after 0 and 7 mo of training. Urine progesterone was sampled weekly throughout. Body composition (dual X-ray absorptiometry), fasting insulin resistance (homeostatic modeling assessment 2, HOMA2), leptin, sex steroids, anti-Müllerian hormone (AMH), and inhibin B were measured after 0, 7, and 11 mo with an additional assessment of body composition at 3 mo. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responses were suppressed after 7 mo (both P < 0.001). Among noncontraceptive users (n = 20), 65% had regular (23-35 days) cycles preenrollment, falling to 24% by 7 mo of training. Of women in whom urine progesterone was measured (n = 24), 87% of cycles showed no evidence of ovulation. There was little change in AMH, LH, and estradiol, although inhibin B and FSH increased (P < 0.05). Fat mass fluctuated during training but at month 11 was unchanged from baseline. Fat-free mass did not change. Visceral adiposity, HOMA2, and leptin increased (all P < 0.001). HPG axis suppression with anovulation occurred in response to training without evidence of low EA. Increased insulin resistance may have contributed to the observed pituitary and ovarian dysfunction. Our findings are likely to represent an adaptive response of reproductive function to the multistressor nature of military training.NEW & NOTEWORTHY We characterized reproductive endocrine adaptation to prolonged arduous multistressor training in women. We identified marked suppression of hypothalamic-pituitary-gonadal (HPG) axis function during training but found no evidence of low energy availability despite high energy requirements. Our findings suggest a complex interplay of psychological and environmental stressors with suppression of the HPG axis via activation of the hypothalamic-pituitary adrenal (HPA) axis. The neuroendocrine impact of nonexercise stressors on the HPG axis during arduous training should be considered.

Breast cancer risk factors in relation to molecular subtypes in breast cancer patients from Kenya.

BACKGROUND: Few studies have investigated risk factor heterogeneity by molecular subtypes in indigenous African populations where prevalence of traditional breast cancer (BC) risk factors, genetic background, and environmental exposures show marked differences compared to European ancestry populations. METHODS: We conducted a case-only analysis of 838 pathologically confirmed BC cases recruited from 5 groups of public, faith-based, and private institutions across Kenya between March 2012 to May 2015. Centralized pathology review and immunohistochemistry (IHC) for key markers (ER, PR, HER2, EGFR, CK5-6, and Ki67) was performed to define subtypes. Risk factor data was collected at time of diagnosis through a questionnaire. Multivariable polytomous logistic regression models were used to determine associations between BC risk factors and tumor molecular subtypes, adjusted for clinical characteristics and risk factors. RESULTS: The median age at menarche and first pregnancy were 14 and 21 years, median number of children was 3, and breastfeeding duration was 62 months per child. Distribution of molecular subtypes for luminal A, luminal B, HER2-enriched, and triple negative (TN) breast cancers was 34.8%, 35.8%, 10.7%, and 18.6%, respectively. After adjusting for covariates, compared to patients with ER-positive tumors, ER-negative patients were more likely to have higher parity (OR = 2.03, 95% CI = (1.11, 3.72), p = 0.021, comparing ≥ 5 to ≤ 2 children). Compared to patients with luminal A tumors, luminal B patients were more likely to have lower parity (OR = 0.45, 95% CI = 0.23, 0.87, p = 0.018, comparing ≥ 5 to ≤ 2 children); HER2-enriched patients were less likely to be obese (OR = 0.36, 95% CI = 0.16, 0.81, p = 0.013) or older age at menopause (OR = 0.38, 95% CI = 0.15, 0.997, p = 0.049). Body mass index (BMI), either overall or by menopausal status, did not vary significantly by ER status. Overall, cumulative or average breastfeeding duration did not vary significantly across subtypes. CONCLUSIONS: In Kenya, we found associations between parity-related risk factors and ER status consistent with observations in European ancestry populations, but differing associations with BMI and breastfeeding. Inclusion of diverse populations in cancer etiology studies is needed to develop population and subtype-specific risk prediction/prevention strategies.

Efecto de la temperatura sobre la morfología y reproducción en el erizo de mar Arbacia dufresnii (Echinodermata: Echinoidea) / Effect of temperature on morphology and reproduction of sea urchin, Arbacia dufresnii (Echinodermata: Echinoidea)

Introducción: El aumento de los valores del CO2 atmosférico y el consecuente calentamiento del agua de mar constituyen factores de estrés para los ecosistemas marinos, renovando el interés en la fisiología de los equinoideos. El equinoideo Arbacia dufresnii es una especie ampliamente estudiada y con amplia distribución en los golfos norpatagónicos. Objetivo: Evaluar el efecto de temperatura del agua de mar sobre su morfología y reproducción. Métodos: Individuos de A. dufresnii fueron expuestos durante 10 semanas (Abril-Junio 2016) a tres tratamientos de temperatura (13 °C control, 15 °C y 17 °C) de acuerdo con las condiciones actuales del agua de mar y los valores esperados para el próximo siglo, según diferentes escenarios estimados. Al finalizar el experimento, diámetro y peso del individuo así como los pesos de los órganos internos fueron estadística e histológicamente analizados. Resultados: Se observó una mayor mortalidad en los individuos expuestos a las mayores temperaturas lo que podría deberse a un estrés en el individuo. Para el tratamiento control y el de 17 °C no se observaron cambios en los pesos secos de gónadas e intestino. En cambio, los individuos expuestos a 15 °C presentaron un aumento en el diámetro del caparazón y en el peso seco de gónadas e intestino. Los estadios gonadales aesta temperatura (15 °C) para machos fueron similares al ambiente a diferencia de las hembras que se observaron estadios más avanzados. Conclusiones: Esto indicaría que 15 °C podría ser la temperatura óptima para la asimilación del alimento y obtención de energía. A esta temperatura se observan cambios a corto plazo en los órganos de metabolismo rápido pero no en los órganos calcificados (caparazón y linterna de Aristóteles).

Introduction: The increase in atmospheric CO2 values and the consequent warming of seawater constitute stressors for marine ecosystems, renovating interest in echinoid physiology. The echinoid Arbacia dufresnii is a widely studied species with a wide distribution in the North Patagonian gulfs. Objective: Evaluate the effect of seawater temperature on its morphology and reproduction. Methods: Individuals were exposed for 10 weeks (April-June 2016) to three temperature treatments (13 °C control, 15 °C and 17 °C) according to the current conditions of seawater and the expected values for the next century. At the end of the experiment, diameter and weight of the whole individual and of its internal organs were statistically and histologically analyzed. Results: Individuals exposed to higher temperatures died in greater numbers. The control, and the 17 °C treatment, had no changes in dry gonad and intestine weights. However, the 15 °C group had wider diameter of test and a higher dry weight of gonads and intestine. At this temperature, the gonadal stages for males were similar to the environment, but females had more advanced stages. Conclusions: Temperature of 15°C could be optimal for assimilating food and obtaining energy. Gonads and intestine would be showing changes in the short term, unlike the calcified organs (test and Aristotle's lantern).

Molecular docking and dynamics simulation to screen interactive potency and stability of fungicide tebuconazole with thyroid and sex hormone-binding globulin: Implications of endocrine and reproductive interruptions.

Tebuconazole is a widely used fungicide in agriculture, and it may easily enter in the human food chain. In addition, tebuconzaol skin permeation coefficient (Log Kp) is -5.55 cm/s and it does not violate Lipinski's rule. It may mimic as a ligand for various endocrine and reproductive receptor leading to toxicological response or disease manifestation. We studied interactive potential of tebuconazole with thyroid and sex hormone-binding globulin. The main methods for this in silico analyses are molecular docking and molecular dynamic (MD) simulation. This paper explores how agriculture fungicide tebuconzaol exposure can be a risk for endocrine and reprotoxicity due to its stable interactive potency with thyroid and sex hormone-binding globulin (2CEO and 1D2S). Thyroid impairment is one of the most common endocrine issues in human health. In molecular docking analyses, tebuconazole exhibited binding potency of -6.28 kcal/mol with 2CEO compared to its native ligand thyroxin and inhibitor propylthiouracil which had the binding potency of -9.9 and -4.49 kcal/mol, respectively. The binding score of tebuconzaol with 1D2S was found to be -7.54 kcal/mol compared to native ligand dihydrotestosteron and inhibitor aminoglutethimide which exhibited the binding score of -6.84 and -11.41 kcal/mol, respectively. Therefore, each complex was subjected to MD simulation for comparative assessment of physical movement. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), Radius of Gyration and hydrogen bonding exhibited that fluconazole had stable binding pattern with 2CEO and 1D2S which was almost similar to native ligand and its inhibitor. Study revealed that tebuconazole may lead to potent endocrine and reproductive disruptions.

A case-control study of the joint effect of reproductive factors and radiation treatment for first breast cancer and risk of contralateral breast cancer in the WECARE study.

OBJECTIVE: To examined the impact of reproductive factors on the relationship between radiation treatment (RT) for a first breast cancer and risk of contralateral breast cancer (CBC). METHODS: The Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study is a multi-center, population-based case-control study where cases are women with asynchronous CBC (N = 1521) and controls are women with unilateral breast cancer (N = 2211). Rate ratios (RR) and 95% confidence intervals (CI) were estimated using conditional logistic regression to assess the independent and joint effects of RT (ever/never and location-specific stray radiation dose to the contralateral breast [0, >0-<1Gy, ≥1Gy]) and reproductive factors (e.g., parity). RESULTS: Nulliparous women treated with RT (≥1Gy dose) were at increased risk of CBC compared with nulliparous women not treated with RT, although this relationship did not reach statistical significance (RR = 1.34, 95% CI 0.87, 2.07). Women treated with RT who had an interval pregnancy (i.e., pregnancy after first diagnosis and before second diagnosis [in cases]/reference date [in controls]) had an increased risk of CBC compared with those who had an interval pregnancy with no RT (RR = 4.60, 95% CI 1.16, 18.28). This was most apparent for women with higher radiation doses to the contralateral breast. CONCLUSION: Among young female survivors of breast cancer, we found some evidence suggesting that having an interval pregnancy could increase a woman's risk of CBC following RT for a first breast cancer. While sampling variability precludes strong interpretations, these findings suggest a role for pregnancy and hormonal factors in radiation-associated CBC.

Pulmonary Emphysema Impairs Male Reproductive Physiology Due To Testosterone and Oxidative Stress Imbalance in Mesocricetus auratus.

This study evaluated whether pulmonary emphysema affects sperm quality, male reproductive organs, and testosterone levels in adult male hamsters. Mesocricetus auratus males (130-150 g) were subdivided into a control group (C group) and an emphysema group (E group). The C group received an intratracheal instillation of saline solution (0.3 mL/100 g of body weight), and the E group received papain (40 mg/100 g of body weight). After 60 days, the biometric, pulmonary, and reproductive parameters of each group were evaluated. The E group developed pulmonary emphysema, which decreased body weight and sperm quality compared to the C group. In oxidative stress-related assays, lipid peroxidation was increased in the testis and epididymis (caput and cauda) in the E group compared with the C group. However, only the caput epididymis showed a reduction in glutathione levels. Pulmonary emphysema also affected the testicle by inducing an increase in abnormal seminiferous tubules, accompanied by a decrease in seminiferous epithelium height. Spermatogenesis kinetics were also modified by pulmonary emphysema. The number of Leydig and Sertoli cells decreased in the E group, accompanied by an increase in the nuclear volume of Leydig cells. Testosterone concentration was increased in the E group. Similarly, pulmonary emphysema altered epididymal components in all regions. In conclusion, pulmonary emphysema affected the reproductive system in this experimental model, as shown by testicular and epididymal morphophysiology changes, hormonal alteration, and oxidative stress imbalance, inducing the loss of correct function in the male reproductive system.

Effects of BRCA gene mutation on female reproductive potential: A systematic review.

Mutation of BRCA genes significantly increases the lifetime risk of breast, ovarian, fallopian tube and primary peritoneal cancers. In addition to the increased risk of these multiple malignancies, the recent literature suggests that mutations in BRCA genes may lead to decreased reproductive potential. In this systematic review, we focus on the effect of BRCA gene mutation on reproductive potential. The main outcomes included the rate of nulliparity, ovarian reserve, ovarian response, and the age at natural menopause. A total of 23 observational studies were included for quality analysis. The certainty of evidence was low to moderate: the main limitations were imprecision and statistically significant heterogeneity. Meta-analysis suggested that the rate of nulliparity, serum anti-müllerian hormone levels, antral follicle counts and ovarian response were not significantly affected in BRCA gene mutation carriers (P > 0.05). BRCA gene mutation carriers tended to have a lower number of primordial follicles (P = 0.0002) and lower age at natural menopause than non-carriers. In conclusion, there is no compelling evidence indicating that the rate of nulliparity, serum AMH, antral follicle counts and ovarian response are affected in BRCA mutation carriers.

Decreased bone mineral density and reproductive axis dysfunction: more than oestrogen.

Decreased bone mineral density (BMD) in oestrogendeficient states has long been thought to be a direct outcome of the reduction in oestrogen. In physiologic and many pathologic hypo-oestrogenic states, oestrogen supplementation improves BMD. However, the relationship between oestrogen replacement and BMD is less clear in the case of reproductive axis dysfunction secondary to decreased caloric intake or increased energy expenditure, such as in female athletes or anorexia nervosa. This decrease in oestrogen is associated with decreased BMD, but oestrogen replacement in these states fails to conclusively improve BMD. This suggests that the decrease in BMD in these states is not driven solely by low oestrogen. Cortisol and other markers of inflammation may play a role in BMD reduction but further research is needed. What is clear is that increased caloric consumption and restoration of menses and the reproductive axis are essential to improving BMD, while pharmacologic therapy, including oestrogen replacement through hormone therapy or contraceptives, does not provide conclusive benefit.

Reproductive Risk Factors of Inflammatory Breast Cancer according to Luminal, HER2-Overexpressing, and Triple-Negative Subtypes: A Case Comparison Study.

OBJECTIVE: We evaluated the risk factors of inflammatory breast cancer (IBC) compared to non-IBC and according to histological subtype. METHODS: Cases of IBC (n = 160) and controls of non-IBC (n = 580) were collected from the cohort of breast cancer patients treated in two oncology centers matched based on age at cohort entry. Data about breast cancer risk factors were collected. We evaluated correlation and ORs using conditional logistic regression analysis for each case group versus the control group. We also evaluated those factors in three further subgroups: luminal (HR+, HER2-), HER2-overexpressing (HER2+, HR-), and triple-negative (TN) patients. RESULTS: Long duration of breastfeeding of ≥12 months (OR = 4.64, 95% CI 2.97-7.26), body mass index ≤25 (OR = 2.48, 95% CI 1.71-3.58), and use of oral contraceptives (OR = 2.48, 95% CI 1.62-3.84) were the most significant risk factors in favor of IBC compared to non-IBC. There was no impact of contraceptives use in the luminal subgroup and no impact of long duration of breastfeeding in the TN subgroup. The role of socioeconomic and educational levels was unclear. Age at menarche, age at first pregnancy, and age at menopause were nonsignificant risk factors of IBC. CONCLUSION: Reproductive risk factors were distinct in IBC patients reflecting the clinical entity of IBC.

Establishment of NOAEL for intracavernous injections of human bone marrow-derived mesenchymal stem cells in rats.

Purpose: To assess the possible negative health effects of human bone marrow-derived mesenchymal stem cells (hBMSCs) on fertility and early embryonic development following intracavernous injections in rats. Materials and Methods: A total of 88 Crl:CD(SD) male and female rats were equally divided into 4 groups in a random manner: control group (normal saline), low-dose group (2×105 hBMSCs), moderate-dose group (1×106 hBMSCs), and high-dose group (2×106 hBMSCs). hBMSCs or normal saline was injected into the penis of the rats 3 times at 2-week-intervals prior to mating. We compared each group with respect to parameters of reproduction and histopathology. Results: For male rats, various degrees of flushing and swelling were observed at the penile injection site in all the groups, although the severity increased in a dose-dependent manner in the hBMSC injection groups. There were no statistically significant differences in mean body weights and food consumption among all the groups of both sexes. There were no statistically significant differences in reproductive parameters among all the groups of both sexes. The absolute and relative organ weights did not significantly differ among the groups. At the time of necropsy, no remarkable findings were observed in gross examinations in all groups. On histopathological analysis, minimal mononuclear cell infiltration was observed in the right epididymis of each rat in the moderate- and high-dose groups. Conclusions: The non-toxic amount of hBMSCs for male fertility and early embryogenesis in rats under the test conditions was determined to be 2×106 cells/head.

Reproductive Senescence and Ischemic Stroke Remodel the Gut Microbiome and Modulate the Effects of Estrogen Treatment in Female Rats.

Our previous work has shown that reproductively senescent (or middle-aged; 10-12-month-old) Sprague-Dawley female rats, that are naturally estrogen-deficient, have worse stroke outcomes as compared to normally estrous-cycling adult (5-6-month-old) females. Paradoxically, estrogen replacement to this middle-aged group exacerbates stroke outcomes, while it is neuroprotective in adult females. Recent studies reveal an important role for the gut microbiome and gut metabolites in cardiovascular health, including stroke outcomes. To determine whether gut dysbiosis underlies stroke severity in reproductive senescent females, and underlies the anomalous effects of estrogen on stroke, we compared the gut microbiota and gut metabolites pre and post stroke in (a) gonadally intact adult and middle-aged females, (b) in ovariectomized and estrogen-treated (OVX+E) adult and OVX+E middle-aged females, and (c) in middle-aged OVX+E females after fecal microbiome transfer. Our data show significant gut dysbiosis in reproductive senescent females at baseline and after stroke as indicated by an elevated ratio of the major phyla, Firmicutes/Bacteroidetes (F:B), reduced alpha diversity, and significant shifts in beta diversity as compared with adult females. Specific bacterial families were also altered as a result of reproductive aging, as well as gut metabolites, including elevated serum endotoxin levels and decreased short-chain fatty acids (SCFAs), with a concomitant increase in IL-17A, indicating that reproductive senescence significantly affects gut communities under pathologic conditions. Despite the differences in gonadally intact adult and middle-aged females, estrogen-treated ovariectomized (OVX+E) females of either age group displayed no differences in the major phyla, but there was increased abundance in specific bacterial taxa, including Prevotella and Lactobacillus. The SCFA butyrate was significantly reduced at baseline in the middle-aged OVX+E females, while circulating endotoxin LPS were elevated in this group after stroke, suggesting that gut metabolites were differently affected by estrogen treatment in the two age groups. A fecal transfer from adult OVX+E females to middle-aged OVX+E females significantly reduced infarct volume, improved behavioral recovery and transiently reduced IL-17A expression. These data provide the first evidence that microbial gut communities and metabolites are altered by reproductive senescence in female rats at baseline and after stroke, and suggest that estrogen may impact stroke recovery differently in adult and reproductive senescent females due to an age-specific effect on gut microbiota and metabolites.