Removal Of Gonads Research Articles

Androgen insensitivity syndrome: preventive gonadectomy, pros and cons

Androgen insensitivity syndrome is a genetic disorder characterized by complete or partial androgen insensitivity in individuals with a 46XY genotype. It is also the most common cause of disorders of sexual differentiation in patients with a 46XY karyotype. This condition is caused by a defect in the androgen receptor gene (AR), leading to abnormal development of male genitalia, impaired formation of male secondary sexual characteristics, and phenotypic features resembling the female sex.One of the important aspects related to the management of androgen insensitivity syndrome is the necessity of preventive gonadectomy. However, the rationale for prophylactic removal of gonads remains a subject of debate. This article presents a clinical case of a 37-year-old woman with complete androgen insensitivity syndrome who, despite recommendations for gonadectomy based on suspicious MRI characteristics of the gonads, made the decision to decline surgical intervention, justifying her choice by the positive impact of gonadal hormonal activity on her external appearance and physical characteristics. This clinical case highlights the complexity of decision-making in the management of androgen insensitivity syndrome, where patient preferences and needs may play a significant role, despite potential risks and concerns surrounding the preservation of gonads.

Comparative evaluation of the serum biochemical and lipid profile changes in spayed male and female rats

Background and aims: This study investigated the effects of gonadal removal in male and female rats on changes in serum biochemical parameters. Methods: Twenty-eight adult male and female rats were divided into four groups of 7 animals for a period of 9 weeks. The first and second groups of intact male and female rats, as well as the third and fourth groups of male and female rats, were gonadectomized, respectively. At the end of the ninth week of the study, the rats were anesthetized with chloroform, and the amount of glucose, some lipid parameters in serum, and the activity of a number of serum enzymes were measured after taking blood from the heart. Results: Alanine aminotransferase, and alkaline phosphatase (ALP) levels were higher in intact male rats than in intact female rats, respectively (P=0.03, P=0.015). The amounts of glucose and cholesterol of low-density lipoprotein (LDL) in intact female rats were higher than in the ovariectomized rats, respectively (P=0.07, P=0.039, P=0.03). The amount of lactate dehydrogenase (LDH) in spayed female rats demonstrated a significant increase compared to other groups (P=0.001). However, there was a significant decrease in calcium levels in gonadectomized rat groups in comparison to intact female rats (P=0.02). Finally, a significant increase was found in phosphorous levels in the intact male rats group compared to other groups (P=0.002). Conclusion: Decreased sex hormones in gonadectomized rats compared with intact rats could lead to increased serum levels of LDH, ALP, and LDL cholesterol that may result in the development of metabolic and atherogenesis syndromes and acute liver failure.

SAT395 Gender Dysphoria In A Patient With Ovotesticular Disorder Of Sex Development

Abstract Disclosure: T. Moreno: None. P. Rodrigues: None. S. Ribeiro: None. D.M. Carvalho: None. Introduction: Ovotesticular disorder of sex development (OT-DSD) is a rare condition characterized by the presence of both ovarian and testicular tissue in the gonads. Management and sex designation of these patients depend on several factors and an underlying potential for gender dysphoria should be acknowledged.Clinical Case: A 12-month-old patient from Guinea-Bissau, born from consanguineous parents, was referred to Pediatric Surgery due to atypical genitalia. Karyotype was 46,XX and SRY gene analysis was negative. Genitoscopy showed absence of a vagina and a uterus was not found on magnetic resonance imaging. An exploratory laparotomy and biopsy of the gonads was performed. The pathology report confirmed the presence of gonadal ovarian and testicular tissue, establishing the diagnosis of OT-DSD. Surgical removal of both gonads and clitoroplasty was performed and a female sex designation was attributed. Endocrinology follow-up was started at the age of 8 and the first physical examination revealed weight 48.6 kg (> P97), height 135.5 cm (P90–97); Tanner stage I (P1A1M0) and a blind vagina with normal clitoris size. Blood tests showed FSH 12.53 mUI/L, LH 1.07 mUI/L, estradiol 5.8 pg/mL and total testosterone 0.04 ng/mL. Reconstructive surgery for a neovagina was performed at 13-years-old and, two years later, the patient was started on hormone replacement therapy with transdermic estradiol. At the age of 16, the patient manifested gender dysphoria issues, decided to stop estradiol and was referred for psychiatric evaluation. Two years later, intramuscular testosterone enanthate was initiated but treatment was stopped after a six-month trial, as the patient claims to identify as male but is not interested in seeking hormone treatment at this point.Conclusion: OT-DSD is an uncommon condition, raising issues of gender assignment that are dependent on factors such as age at diagnosis, phenotype, internal structures and reproductive potential. Scarce data exists on long-term outcomes in OT-DSD, including the frequency of gender dysphoria in these patients. Gender identity is an important factor to consider on long-term follow-up of OT-DSD patients. Presentation: Saturday, June 17, 2023

Correlates of estimated lifetime cruciate ligament survival inform potential rupture risk reduction strategies: findings from the Exceptional Aging in Rottweilers Study

Cranial cruciate ligament (CCL) rupture is one of the most commonly diagnosed orthopedic conditions of pet dogs, making estimated lifetime cruciate ligament survival an attractive endpoint for studies attempting to define clinical and genetic correlates of rupture risk reduction. Early life experiences contribute significantly to the origins of adult health outcomes, yet our current understanding of modifiable susceptibility factors that drive the high frequency of CCL rupture remains limited. We reasoned that combining lifetime medical history with standardized late-life assessment of lifetime cruciate ligament survival and detailed phenotyping of each dog for selected risk variables would provide a sensitive approach to identify factors that would differentiate between lifelong avoidance versus susceptibility to ligament rupture. Here, we report results of Kaplan–Meier analysis of estimated lifetime cruciate ligament survival and Cox proportional hazards modeling to assess risk variables in a lifetime cohort study of 123 purebred Rottweilers, a breed at high risk for veterinarian-diagnosed CCL rupture. We show that gonad removal during the 24-month developmental period is adversely associated with three measures of susceptibility—increased incidence of CCL rupture, multiplicity (bilateral rupture), and accelerated time to initial CCL failure. Our analysis reveals two other phenotypes—short adult height and the production of offspring (in females)—are associated with significant CCL rupture risk reduction. Together, the results provide clues to an early endocrine influence on lifetime cruciate ligament survival. Further, we identify two distinct clinical syndromes of CCL failure, providing a disease subtyping framework to advance future progress in genetic epidemiology, pathogenesis, and prediction. By conducting an evaluation of estimated lifetime CCL survival in dogs, we show that cruciate ligament survival may be jeopardized by gonad removal during the developmental period. Avoidance of such early environmental adversity may represent an actionable method for the control of canine CCL disease in certain breeds.

Interest In and Prior Receipt of Counseling on Fertility Preservation in Transgender Patients Presenting for Gender-affirming Orchiectomy

To describe the characteristics of patients presenting for gender-affirming bilateral simple orchiectomy including interest in and prior education on reproductive options prior to gonad removal. A retrospective chart review evaluated patients seeking gender-affirming bilateral orchiectomy. Data collected included age, family history, history of fertility preservation education prior to gender-affirming hormone therapy initiation, prior fertility preservation, interest in fertility preservation, and postorchiectomy surgical pathology results where applicable. The cohort included 78 patients. 22% (n=17) indicated reproductive options were not discussed prior to surgical consultation. 85% (n=66) were not interested in fertility preservation. Reasons included not having an interest in biological children (74%), not wanting to delay transition (47%), and cost (36%). Patients who were married or in long-term relationships had a higher interest in fertility preservation compared to patients who were not in long-term relationships. 40% of patients with pathology data available had at least some level of spermatogenesis present in their testicular tissue. Fertility preservation counseling prior to surgical referral was lower than expected. This lack of counseling could result in patients not wanting to sperm bank prior to orchiectomy as it could delay their surgical care. Increased adherence to the WPATH guidelines may improve fertility preservation interest. Our data shows a low utilization and interest in sperm preservation for transwomen and nonbinary patients seeking bilateral simple orchiectomy at our institution. Improving counseling regarding fertility preservation options earlier in transition could improve utilization of sperm cryopreservation.

Understanding the effects of sustained supraphysiologic concentrations of luteinizing hormone in gonadectomized dogs: What we know and what we still need to learn

Removal of the gonads with surgical sterilization results in a loss of negative feedback to the hypothalamus and anterior pituitary. The sustained supraphysiologic luteinizing hormone (LH) concentrations in gonadectomized dogs can significantly alter organ function and even induce neoplastic changes. For example, gonad removal has a profound effect on thyroid function and is reported to be the most significant cause for the development of hypothyroidism in dogs. Thirty percent more gonadectomized dogs develop hypothyroidism compared with intact dogs. Within the canine thyroid, LH receptors are co-localized with thyroid stimulating hormone (TSH) receptors. Continuous LH receptor activation in gonadectomized dogs may interfere TSH receptor function by consuming second messengers involved in G-protein receptor cell signaling, preventing the action of TSH when it binds to its receptor in the thyroid, resulting in hypothyroidism. The incidence of anterior cruciate ligament ruptures is significantly increased following gonad removal independent of breed, sex, weight or body condition. Luteinizing hormone receptors are expressed in the cruciate ligament and continuous LH receptor activation may increase laxity in these ligaments, resulting in joint instability. Both male and female gonadectomized dogs are at a significantly increased risk for lymphoma and hemangiosarcoma. Luteinizing hormone receptors are also abundant in these tissues. Research in four canine hemangiosarcoma cell lines found that LH receptor activation induces cell proliferation. In addition, research in three canine T-cell lymphoma cell lines found that LH receptor activation induces cell proliferation, adhesion, and invasion as well as increases LH receptor expression. Research is needed to determine if LH reducing strategies using gonadotropin releasing hormone agonists will increase remission times in gonadectomized dogs with LH receptor-positive tumors. In conclusion, among the non-reproductive functions of gonads, suppression of LH secretion and resulting LH receptor overexpression appear necessary in maintaining endocrine, musculoskeletal, and anti-neoplastic health.

성분화질환자의 성별 자기결정권 확보방안

The gender of the son, according to the purpose of United Nations Convention on the Rights of the Child, Article 12, should be determined after considering his opinion in accordance with age and maturity, and then, the son should determine the gender with accurate and enough information to form his opinion about the gender. The son has the right to acquire his gender from the birth, and the parents have the right and obligation to determine the gender of their son, and government should not interrupt the gender determination by parents and their son. Therefore, the son whose gender is undecided when he was born also has the right not to be compelled to determine the gender. Under current law, male and female dichotomous system, recognition of third sex, and also the relation of birth registration should be considered to guarantee the right to gender determination of the son who was born sexually undifferentiated, and they are summarized as follows. First, Under current law, male and female dichotomous system of gender shall maintain in principle, and permanent lifetime third sex shall not be recognized. In addition, the establishment of permanent third sex is also not recognized, but maintenance of legal status as gender undetermination should be recognized until when the final decision is made by himself. Second, Under Act on the Registration, etc. of Family Relationship or its practice, the device of birth registration in gender undetermination condition should be prepared, that is to say, not only “male” or “female” but also “gender undetermination” should be prepared for selection option in birth registration form. These writing method is not to recognize permanent third sex but to recognize temporary until when the son grows up and performs his right to gender determination, and completes the gender subsequently in birth registration form. Third, in terms of law, gender determination of the son is the matter how to harmonize the right of the son who lives on and the right and obligation of the parents who bring up. The basic structure is that the right of the parents decreases gradually according to maturity of understanding and judgement of the son, and the right of the parents terminates when the judgement of the son matures enough. In other words, the step theory of gender, which gender is determined by maturity of the son, is that the decision right of the parents terminates and the son has the right to decide when the son has the judgement enough to decide the solution to the problem. However, the gender determination, even if the son can make a final decision applying the principle of mature minor, would influence all over his lifetime and simultaneously his mind and body for a long time unlike consent or refusal of one-time surgical operation. The sexual differentiation of brain of people shall confirm at the age of 2 or 3, so if sexual signs appeared at this time, the parents could determine ‘the sex of nurturing’ and complete the birth registration form subsequently. However, although the gender in birth registration form was completed subsequently at that time, the application of gender change should be recognized in case the son selects the opposite sex. For this, except inevitable reasons, the parents should not perform irreversible surgical operation like gonad removal which would interrupt the final gender determination of the son.

Feminizing genitoplasty for prepubertal children and teenagers female

The aim of this study was to report our experience after 10 years of practice of feminizing genitoplasty in prepubertal and adolescent patients with disorders of sex development (DSD) assigned females as females in a developing country. This was a cross-sectional, descriptive and retrospective study over a period of 9 years. All pre-pubertal (8-12 years) and adolescent patients female sex assigned with DSD who had willfully consented to the surgery with their guardians and underwent feminizing genital surgery were enrolled in the study. Data collection included: age at presentation, precise diagnosis, surgical procedures, complications, cosmetic result and duration of follow-up. Each patient had a precise diagnosis and the surgery was planned after discussion with the multidisciplinary team. Cosmetic results were assessed based on: appearance of the clitoris and separation of the vaginal and urethral openings. Nine patients raised as females with a median age of 8 years (IR: 10.75) were recorded. Surgery was performed at a median age of 11 years (IR: 9.5). In this series, 6 had a 46, XY karyotype with varying diagnoses: partial androgen insensitivity syndrome (n=2); 5-alphareductase insufficiency (n=2); 17-ketoreductase insufficiency (n=2); gonadal dysgenesis with a mutation in the NR5A1 gene (n=2), 2 had ovostesticular DSD, (karyotypes 46, XX), and 1 had mixed gonadal dysgenesis (karyotype 45, X/46, XY). Partial or total gonad(s) removal in accordance with assigned gender was the most common associated procedure. It was bilateral in 7 cases and unilateral in 2 cases. Follow-up ranged from 3 months to 4.5 years (median: 26 months, IR:18.25). One patient had acute urinary retention in the early follow-up. No other complication such as incision bleeding was recorded. The cosmetic appearance of the external genitalia was satisfactory in all patients. Feminizing genital surgery in Cameroon remains a major challenge and should seldom be realized without a precise diagnosis. Late age at presentation is peculiar to our setting; however, it gives room for the patients' participation and input to decisions that will have a life-long personal impact on their lives in terms of psychosocial development and fertility. 3.

17-α-Estradiol Has Sex-Specific Effects on Neuroinflammation That Are Partly Reversed by Gonadectomy.

17-α-Estradiol (17aE2) treatment from 4 months of age extends life span in male mice and can reduce neuroinflammatory responses in the hypothalamus of 12-month-old males. Although 17aE2 improves longevity in males, female mice are unaffected, suggesting a sexually dimorphic pattern of life-span regulation. We tested whether the sex-specific effects of 17aE2 on neuroinflammatory responses are affected by gonadal removal and whether hypothalamic changes extend to other brain regions in old age. We show that sex-specific effects of 17aE2 on age-associated gliosis are brain region specific and are partially dependent on gonadectomy. 17aE2 treatment started at 4 months of age protected 25-month-old males from hypothalamic inflammation. Castration before 17aE2 exposure reduced the effect of 17aE2 on hypothalamic astrogliosis in males. In contrast, sex-specific inhibition of microgliosis generated by 17aE2 was not significantly affected by castration. In the hippocampus, gonadectomy influenced the severity of gliosis and the responsiveness to 17aE2 in a region-dependent manner. The male-specific effects of 17aE2 correlate with increases in hypothalamic estrogen receptor alpha expression, specifically in gonadally intact males, consistent with the idea that 17aE2 might act through this receptor. Our results indicate that neuroinflammatory responses to 17aE2 are partially controlled by the presence of sex-specific gonads. Loss of gonadal function and age-associated neuroinflammation could, therefore, influence late-life health and disease onset, leading to sexual dimorphism in both aging and in response to drugs that modify the pace of aging.

Testosterone-induced increase in libido in a patient with a loss-of-function mutation in the AR gene.

SummaryComplete androgen-insensitivity syndrome (CAIS), a disorder of sex development (46,XY DSD), is caused primarily by mutations in the androgen receptor (AR). Gonadectomy is recommended due to the increased risk of gonadoblastoma, however, surgical intervention is often followed by loss of libido. We present a 26-year-old patient with CAIS who underwent gonadectomy followed by a significant decrease in libido, which was improved with testosterone treatment but not with estradiol. Genetic testing was performed and followed by molecular characterization. We found that this patient carried a previously unidentified start loss mutation in the androgen receptor. This variant resulted in an N-terminal truncated protein with an intact DNA binding domain and was confirmed to be loss-of-function in vitro. This unique CAIS case and detailed functional studies raise intriguing questions regarding the relative roles of testosterone and estrogen in libido, and in particular, the potential non-genomic actions of androgens.Learning pointsN-terminal truncation of androgen receptor can cause androgen-insensitivity syndrome.Surgical removal of testosterone-producing gonads can result in loss of libido.Libido may be improved with testosterone treatment but not with estradiol in some forms of CAIS.A previously unreported AR mutation – p.Glu2_Met190del (c.2T>C) – is found in a CAIS patient and results in blunted AR transcriptional activity under testosterone treatment.

An Ancient Practice but a New Paradigm: Personal Choice for the Age to Spay or Neuter a Dog.

Extensive practice and knowledge of the methods and effects of castration of male livestock and even humans has been widespread since ancient times, but only a few decades ago did neutering (including spaying) become a routine part of canine husbandry. In the US, the 6-month neuter became standard practice. Only recently, however, have some of the consequences of this major physiological alteration become evident. As the data-based study on 35 breeds reveals, there are major breed differences associated with effects of neutering, especially with early neutering, including increased risks of joint disorders and some cancers. The study of mixed-breed dogs reveals that the risk of joint disorders is increased in the large dogs. Implications of breed-specific and sex-specific effects for age of neutering have prompted the consideration of a new paradigm with regard to this practice. This involves focusing on each individual dog when deciding upon the appropriate age of neutering to avoid increasing the risk of a joint disorder or cancer above that inherent for the breed. For many breeds, particularly the smaller dogs, no effects were found for the age of neutering on joint disorders and the cancers followed. In these cases, the caregiver has a wide range of choice for neutering without increasing the dog's risk for these diseases. In the future, additional research may reveal more about other increased risks for age-related cognitive dysfunction or elevated levels of luteinizing hormone caused by gonad removal, and lead to revised guidelines.

The role of bilateral ovariectomy in the impairments of prooxidant-antioxidant balance and renal concentrating capacity in rats in the period of late manifestations of the traumatic disease and the efficacy of hormone replacement therapy

Introduction. Traumatic events are currently considered to be one of the topical issues. The progression of renal failure plays an important role in the pathogenesis of traumatic disease. It is essential to evaluate the ability of renal tubular epithelium to the urine osmotic concentration in order to indicate the direct renal tubular damage. A sodium-free water clearance (S-CH2O) is a sensitive indicator reflecting the kidneys ability to concentrate the urine. It is established that the renal functional state, the resistance of the kidneys to the development of various disorders depends on the estrogen concentration. The key mechanism of the indirect effect of estrogens on the kidneys is via their direct antioxidant action. However, the role of estrogens in the pathogenesis of oxidative and functional impairments of the kidneys in the presence of cranioskeletal trauma is insufficiently studied. There is no data available on the efficacy of hormone replacement therapy under those circumstances.The objective of research: to determine the pro-oxidant-antioxidant balance and renal concentrating capacity following the cranioskeletal trauma model in rats with bilateral ovariectomy in the period of late manifestations of the traumatic disease and evaluate the efficacy of hormone replacement therapy.Material and methods: The experimental studies were conducted on 64 white non-linear female rats weighing 200-220g. The experimental model of hypoestrogenism was performed through the surgical removal of gonads. The rats were subjected to the cranioskeletal model one month after removal of the gonads. Hormone replacement therapy (HRT) was used as a corrective treatment in the separate subgroup of gonadectomized rats subjected to the cranioskeletal trauma. The control groups consisted of intact animals and rats 1 month after removal of the gonads that were not injured. The renal functional state was determined via a water loading test in the control groups of animals and after 1 and 2 months of postrraumatic period. The sodium concentration, as well as the S-CH2O value was measured in serum and urine. The content of thiobarbituric acid reactive substances (TBARs) and catalase activity were determined in renal cortex and medulla. The prooxidant/antioxidant ratio (ProAntidex) was calculated based on the above data.The results and discussion. The conducted studies indicated the considerable decrease in ProAntidex value in renal cortex and medulla in the group of gonadectomized rats compared to the animals without gonadectomy after 1 month of the posttraumatic period, confirming the protective antioxidant role of estrogens in adequate renal function. The cranioskeletal trauma model led to the declined parameter value in renal cortex and medulla in both experimental groups after 1 month of the posttraumatic period. The prooxidant/antioxidant ratio was significantly decreased in the first month following the trauma in the gonadectomized rats as compared to the rats without the gonadectomy, and remained at the same level up to the 2nd month of the posttraumatic period. The identified abnormal value of ProAntidex in the posttraumatic period clearly affected the dynamics of S-CH2O. This parameter was reported as decreased in both experimental groups compared to the control. However, the parameter was substantially decreased 1 and 2 months after trauma under conditions of the gonadectomy. The administration of hexestrol and progesterone to the gonadectomized rats with trauma model resulted in the considerable increase in value of ProAntidex in renal cortex and medulla starting from the 1st day of the posttraumatic period compared to the animals without corrective medication. Moreover, it was accompanied by a statistically significant increase in S-CH2O rate, indicating the enhancement in the functional capacity of the renal tubules.Conclusions. The value of ProAntidex decreases in renal cortex and medulla in the group of gonadectomized female rats after 1 month of the posttraumatic period, and is significantly lower compared to the animals without removal of the gonads. The cranioskeletal trauma model leads to the substantially declined prooxidant/antioxidant ratio value in renal cortex and medulla, which is reported as considerably greater in the group of gonadectomized animals after 1 month of the posttraumatic period, showing no tendency to enhance after 2 months of the experiment. The administration of hormone replacement therapy to the gonadectomized rats is accompanied by the increase in ProAntidex value and S-CH2O rate compared to the animals without corrective medication.

Complete Androgen Insensitivity Syndrome: From Bench to Bed.

Complete androgen insensitivity syndrome (CAIS) is due to complete resistance to the action of androgens, determining a female phenotype in persons with a 46,XY karyotype and functioning testes. CAIS is caused by inactivating mutations in the androgen receptor gene (AR). It is organized in eight exons located on the X chromosome. Hundreds of genetic variants in the AR gene have been reported in CAIS. They are distributed throughout the gene with a preponderance located in the ligand-binding domain. CAIS mainly presents as primary amenorrhea in an adolescent female or as a bilateral inguinal/labial hernia containing testes in prepubertal children. Some issues regarding the management of females with CAIS remain poorly standardized (such as the follow-up of intact testes, the timing of gonadal removal and optimal hormone replacement therapy). Basic research will lead to the consideration of new issues to improve long-term well-being (such as bone health, immune and metabolic aspects and cardiovascular risk). An expert multidisciplinary approach is mandatory to increase the long-term quality of life of women with CAIS.

Protocolo alternativo na utilização do estrógeno de curta duração no tratamento da incontinência urinária em cadela

A incontinência urinária é uma alteração no armazenamento da urina que comumente acomete cadelas castradas. Em virtude da correlação hormonal entre a remoção das gônadas das fêmeas e a incompetência do mecanismo do esfíncter uretral, o tratamento com reposição de estrógeno pode reverter essa condição. Porém, o modo de uso desse hormônio em cadelas é protocolar dentro da posologia do produto. Já a resposta de cada cadela é individual e de acordo com a resposta clínica, variando em quantidade e tempo independente do peso ou porte. Por isso, o objetivo desse relato foi demonstrar uma dose e intervalo de tempo possível no tratamento da incontinência urinária em uma cadela castrada. Foi atendida uma cadela, fêmea, castrada, com aproximadamente 10 anos de idade, apresentando incontinência urinária, e estabilização do quadro clínico com 0,25mg/animal de estriol (Incurin®), a cada 72 horas, demonstrando que a instituição da terapêutica em alguns indivíduos pode diferir acentuadamente do recomendado em bula de 1mg/animal a cada 24 horas.

From Food Waste to Innovative Biomaterial: Sea Urchin-Derived Collagen for Applications in Skin Regenerative Medicine.

Collagen-based skin-like scaffolds (CBSS) are promising alternatives to skin grafts to repair wounds and injuries. In this work, we propose that the common marine invertebrate sea urchin represents a promising and eco-friendly source of native collagen to develop innovative CBSS for skin injury treatment. Sea urchin food waste after gonad removal was here used to extract fibrillar glycosaminoglycan (GAG)-rich collagen to produce bilayer (2D + 3D) CBSS. Microstructure, mechanical stability, permeability to water and proteins, ability to exclude bacteria and act as scaffolding for fibroblasts were evaluated. Our data show that the thin and dense 2D collagen membrane strongly reduces water evaporation (less than 5% of water passes through the membrane after 7 days) and protein diffusion (less than 2% of BSA passes after 7 days), and acts as a barrier against bacterial infiltration (more than 99% of the different tested bacterial species is retained by the 2D collagen membrane up to 48 h), thus functionally mimicking the epidermal layer. The thick sponge-like 3D collagen scaffold, structurally and functionally resembling the dermal layer, is mechanically stable in wet conditions, biocompatible in vitro (seeded fibroblasts are viable and proliferate), and efficiently acts as a scaffold for fibroblast infiltration. Thus, thanks to their chemical and biological properties, CBSS derived from sea urchins might represent a promising, eco-friendly, and economically sustainable biomaterial for tissue regenerative medicine.

Primary amenorrhea with Swyer syndrome: a rare case report

Swyer syndrome with complete gonadal dysgenesis is associated with an absence of testicular differentiation in a phenotypic female with a 46, XY karyotype. The diagnosis is usually made at adolescence when primary amenorrhea is investigated. Here is an interesting case report of 18-year-old unmarried girl, who presented with primary amenorrhea and non-development of breasts. Her body built was musculin with broad shoulders, prominent Adam’s apple and deep voice. Examination of her secondary sexual charaistisctcs revealed no breast development, absent axillary hair and sparse pubic hairs with female type of external genitalia. Laboratoryanalyses revealed serum follicle-stimulating hormone and luteinizing hormone levels compatible with hypergonodotropichypogonadism. Pelvicultrasonography showed an infantile uterus and streak gonads. Chromosome analysis revealed 46, XYkaryotype. Laparoscopic removal of streak gonads was done as there is a risk of gonadoblastoma in such cases. The patient was started on hormonal replacement therapy. Swyersyndrome results mainly due to mutation in certain genes such as SRY gene, which leads to failure of development of testis.
 Birdem Med J 2020; 10(2): 130-132

Gonad-Sparing Surgical Sterilization in Dogs.

Elective sterilization of pet dogs is a common surgical procedure performed in veterinary practice. The main benefit of sterilization is population control and the reduction in euthanasia of unwanted dogs. The most common methods for sterilizing female and male dogs are ovariohysterectomy (spay; which removes both the ovaries and the uterus) and castration (neutering; which involves removing the testicles), respectively. However, any surgery that removes the gonads changes the animal in both positive and negative ways. There is mounting evidence supporting the long-term health complications associated with surgical sterilization with gonad removal. Gonads are not merely gamete-producing or ancillary sex/reproductive organs but rather they are necessary endocrine glands for normal metabolic, behavioral, musculoskeletal, and anti-neoplastic health. The purpose of this mini review is to describe two gonad sparing surgeries that this author has used to sterilize dogs. These surgeries can be performed on pediatric patients without interfering with pubertal maturation. Dog owners can make the decision when the dog is completely mature whether or not the gonads should be removed.

SUN-023 Changes in Microct Bone Density and Reduced Bone Formation in a “Postmenopausal” PCOS Rat Model

Polycystic ovary syndrome (PCOS) affects women during their entire lifespan. Evidence from the literature suggests an association of PCOS with decreased bone formation markers (osteocalcin and P1NP), although no conclusive data about the incidence of fractures exist. In the present study, we investigated the consequences of androgenization in rats on bone markers and femur microCT and the changes in these parameters after ovariectomy. This study was approved by the local Animal Ethics Committee. Briefly, Wistar rats (n= 38) were divided in 4 groups: 1) “Control OVX” (single dose of corn oil s.c. at day 5 of life and ovariectomy at day 100, n=9); 2) “Control SHAM” (n=9); 3) “Androgenized OVX”(single dose of testosterone propionate 1.25 mg s.c. at day 5 of life and ovariectomy at day 100, n=10); and 4) “Androgenized SHAM” (n=10). Full characterization of estrous cycles and weight was performed during growth, and all animals were euthanized at day 180 during metestrus/diestrous. Evaluation of glucose levels, lipids, estradiol, P1NP levels (a marker of bone formation), and analysis of the femur micro CT Skyscan 1174 (Aartselaar, Belgium) was performed in at least eight animals of each group. Ovariectomy increased the weight of Androgenized OVX rats on day 180: these animals were heavier than Control OVX, Control SHAM, or Androgenized SHAM (ANOVA p<0.001). However, metabolic changes were observed in ovary-intact Androgenized SHAM rats who exhibited higher total cholesterol (ANOVA p<0.001), increased LDL (ANOVA p=0.03), and elevated TyG index, a marker of insulin resistance (ANOVA p<0.001) against all other three groups. This group (Androgenized SHAM rats)also exhibited an increase in MicroCt bone density (g/cm-3) (mean + SEM) of 1.117 + 0.06 against the other - Control SHAM 0.8433 + 0.03, Control OVX 0.5527 + 0.001, and Androgenized OVX 0.6284 + 0.02 (ANOVA p< 0.001). Although the values of bone density between Control OVX and Androgenized OVX groups were similar, gonadal removal produced a different pattern of bone density reduction between Control OVX and Androgenized OVX (Two-Way ANOVA p=0.001). Moreover, we found P1NP levels significantly decreased in the Androgenized OVX group (mean + SEM) of 58.57 + 4.41 ng/ml against 88.02 + 8.49 ng/ml in Control OVX versus (ANOVA p<0.0001) indicating lower bone formation. Our results suggest that bone and metabolic features of Androgenized rats are affected by ovariectomy with a negative impact on bone formation.

17β-hydroxysteroid dehydrogenase type 3 deficiency: female sex assignment and follow-up

Deficiency of 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) is a rare autosomal recessive 46,XY disorder of sex development (DSD). It is due to pathogenetic variants in the HSD17B3 gene. Mutated genes encode an abnormal enzyme with absent or reduced ability to convert Δ4-androstenedione (Δ4-A) to testosterone (T) in the fetal testis. Affected individuals are usually raised as females and diagnosis is made at puberty, when they show virilization. A girl with a presumptive diagnosis of complete androgen insensitivity syndrome underwent endocrine and genetic assessment. Long-term follow-up was reported. The diagnosis of 17β-HSD3 deficiency was made (stimulated T/Δ4-A ratio: 0.15; HSD17B3 gene analysis: c.277+4A>T in intron 3/c.640_645del (p.Glu214_Glu215del) in exon 9. After extensive information, parents decided to maintain female sex. Gonadal removal was performed and histological evaluation demonstrated deep fibrosis of testicular tissue. Follow-up till 8.5years of age showed somatic and neuro-psychological development fitting with the female sex. Management of a child with the rare 17β-HSD3 deficiency remains challenging. Any decision must be carefully evaluated with parents. Long-term follow-up must be warranted by a multidisciplinary DSD team to evaluate the adequacy of the choices made on quality of life in later life.

Fertility Preservation for Pediatric and Adolescent Patients With Cancer: Medical and Ethical Considerations.

Many cancers presenting in children and adolescents are curable with surgery, chemotherapy, and/or radiotherapy. Potential adverse consequences of treatment include sterility, infertility, or subfertility as a result of gonad removal, damage to germ cells as a result of adjuvant therapy, or damage to the pituitary and hypothalamus or uterus as a result of irradiation. In recent years, treatment of solid tumors and hematologic malignancies has been modified in an attempt to reduce damage to the gonadal axis. Simultaneously, advances in assisted reproductive technology have led to new possibilities for the prevention and treatment of infertility. This clinical report reviews the medical aspects and ethical considerations that arise when considering fertility preservation in pediatric and adolescent patients with cancer.