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BioRxiv : the Preprint Server For... Jun 2024Many transgender youth seek gender affirming care, such as puberty suppression, to prolong decision-making and to align their physical sex characteristics with their...
UNLABELLED
Many transgender youth seek gender affirming care, such as puberty suppression, to prolong decision-making and to align their physical sex characteristics with their gender identity. During peripubertal growth, connective tissues such as tendon rapidly adapt to applied mechanical loads (e.g., exercise) yet if and how tendon adaptation is influenced by sex and gender affirming hormone therapy during growth remains unknown. The goal of this study was to understand the how pubertal suppression influences the structural and functional properties of the Achilles tendon using an established mouse model of transmasculine gender affirming hormone therapy. C57BL/6N female-born mice were assigned to experimental groups to mimic gender-affirming hormone therapy in human adolescents, and treatment was initiated prior to the onset of puberty (at postnatal day 26, P26). Experimental groups included controls and mice serially treated with gonadotropin release hormone analogue (GnRHa), delayed Testosterone (T), or GnRHa followed by T. We found that puberty suppression using GnRHa, with and without T, improved the overall tendon load capacity in female-born mice. Treatment with T resulted in an increase in the maximum load that tendon can withstand before failure. Additionally, we found that GnRHa, but not T, treatment resulted in a significant increase in cell density at the Achilles enthesis.
NEW & NOTEWORTHY
These findings demonstrate that puberty suppression or testosterone does not negatively influence tendon structural or functional properties in a mouse model of transmasculine gender affirming care. In all treatment groups, the ability of the tendon to withstand load was significantly increased. Puberty suppression with GnRHa significantly increased enthesis cell density, suggesting an extended growth phase. These findings elucidate the effects of gender affirming care on the structural and functional properties of the tendon and enthesis.
PubMed: 38915724
DOI: 10.1101/2024.06.10.598308 -
Kidney International Reports Jun 2024Growth failure is considered the most important clinical outcome parameter in childhood chronic kidney disease (CKD). Central to the pathophysiology of growth failure is...
INTRODUCTION
Growth failure is considered the most important clinical outcome parameter in childhood chronic kidney disease (CKD). Central to the pathophysiology of growth failure is the presence of a chronic proinflammatory state, presumed to be partly driven by the accumulation of uremic toxins. In this study, we assessed the association between uremic toxin concentrations and height velocity in a longitudinal multicentric prospective pediatric CKD cohort of (pre)school-aged children and children during pubertal stages.
METHODS
In a prospective, multicentric observational study, a selection of uremic toxin levels of children (aged 0-18 years) with CKD stage 1 to 5D was assessed every 3 months (maximum 2 years) along with clinical growth parameters. Linear mixed models with a random slope for age and a random intercept for child were fitted for height (in cm and SD scores [SDS]). A piecewise linear association between age and height was assumed.
RESULTS
Data analysis included data from 560 visits of 81 children (median age 9.4 years; 2/3 male). In (pre)school aged children (aged 2-12 years), a 10% increase in concurrent indoxyl sulfate (IxS, total) concentration resulted in an estimated mean height velocity decrease of 0.002 SDS/yr ( < 0.05), given that CKD stage, growth hormone (GH), bicarbonate concentration, and dietary protein intake were held constant. No significant association with height velocity was found in children during pubertal stages (aged >12 years).
CONCLUSION
The present study demonstrated that, especially IxS contributes to a lower height velocity in (pre)school children, whereas we could not find a role for uremic toxins with height velocity during pubertal stages.
PubMed: 38899199
DOI: 10.1016/j.ekir.2024.03.021 -
JCEM Case Reports Jun 2024OMIM 273750 (3-M) syndrome is a rare cause of severe short stature with variable dysmorphic features caused by pathogenic variants in several genes including cullin7...
OMIM 273750 (3-M) syndrome is a rare cause of severe short stature with variable dysmorphic features caused by pathogenic variants in several genes including cullin7 gene (). Hypogonadism and hypospadias have been described in only a few males. We report a patient with 7 pathogenic variant who had bifid scrotum and perineal hypospadias at birth. He entered puberty spontaneously at age 12 years and appropriately completed pubertal development by 15 years. Subsequently, a regression of testicular volumes, increased gonadotropin levels, and reduced (although normal) testosterone levels were observed. This case highlights the importance of careful pubertal monitoring as pubertal dysfunction may be associated with 3-M syndrome.
PubMed: 38847008
DOI: 10.1210/jcemcr/luae084 -
Reproductive Sciences (Thousand Oaks,... May 2024Endometriosis is often diagnosed in reproductive aged women with spontaneous ovarian activity. Here we described a case of endometriosis diagnosed in a patient with...
Endometriosis is often diagnosed in reproductive aged women with spontaneous ovarian activity. Here we described a case of endometriosis diagnosed in a patient with premature ovarian insufficiency (POI) due to prepubertal bone marrow transplant (BMT). The patient is a 22-year-old nulligravid female who presented with chronic pelvic pain. She had an inherited bone marrow failure syndrome (Diamond-Blackfan anemia), which required gonadotoxic chemotherapy for BMT at a young age prior to puberty. At age 13, she received hormone therapy with transdermal estrogen with subsequent addition of cyclic progestin and was later transitioned to combined oral contraceptive pills (COC). Endometriosis was suspected due to progressive dysmenorrhea and multiple cyclic systemic symptoms. She underwent a trial of elagolix, but could not tolerate it due to worsened arthralgia. Norethindrone acetate (NET-A) was then started, and she underwent diagnostic laparoscopy. Laparoscopy revealed scattered superficial endometriotic lesions in the pelvis. Histological studies showed florid endometriosis. Patient continues on NET-A 10mg and oral estradiol 0.5mg daily since the surgery and has experienced sustained improvement in her symptoms. Endometriosis should be considered as a possible cause for progressive dysmenorrhea or pelvic pain, even in the setting of POI. The balance between HT for overall health benefits in young women with POI and the risk of endometriosis exacerbation is delicate, but achievable.
PubMed: 38806998
DOI: 10.1007/s43032-024-01601-z -
Molecular Human Reproduction May 2024Uterine glands are branched, tubular structures whose secretions are essential for pregnancy success. It is known that pre-implantation glandular expression of leukemia...
Uterine glands are branched, tubular structures whose secretions are essential for pregnancy success. It is known that pre-implantation glandular expression of leukemia inhibitory factor (LIF) is crucial for embryo implantation; however, the contribution of uterine gland structure to gland secretions, such as LIF, is not known. Here, we use mice deficient in estrogen receptor 1 (ESR1) signaling to uncover the role of ESR1 signaling in gland branching and the role of a branched structure in LIF secretion and embryo implantation. We observed that deletion of ESR1 in neonatal uterine epithelium, stroma, and muscle using the progesterone receptor PgrCre causes a block in uterine gland development at the gland bud stage. Embryonic epithelial deletion of ESR1 using a Müllerian duct Cre line, Pax2Cre, displays gland bud elongation but a failure in gland branching. Reduction of ESR1 in adult uterine epithelium using the lactoferrin-Cre (LtfCre) displays normally branched uterine glands. Unbranched glands from Pax2Cre Esr1flox/flox uteri fail to express glandular pre-implantation Lif, preventing implantation chamber formation and embryo alignment along the uterine mesometrial-antimesometrial axis. In contrast, branched glands from LtfCre Esr1flox/flox uteri display reduced expression of ESR1 and glandular Lif resulting in delayed implantation chamber formation and embryo-uterine axes alignment but mice deliver a normal number of pups. Finally, pre-pubertal unbranched glands in control mice express Lif in the luminal epithelium but fail to express Lif in the glandular epithelium, even in the presence of estrogen. These data strongly suggest that branched glands are necessary for pre-implantation glandular Lif expression for implantation success. Our study is the first to identify a relationship between the branched structure and secretory function of uterine glands and provides a framework for understanding how uterine gland structure-function contributes to pregnancy success.
Topics: Animals; Female; Embryo Implantation; Uterus; Mice; Leukemia Inhibitory Factor; Estrogen Receptor alpha; Pregnancy; Mice, Knockout; Signal Transduction
PubMed: 38788747
DOI: 10.1093/molehr/gaae020 -
Current Issues in Molecular Biology May 2024Disorders/differences of sex development (DSDs) are defined as broad, heterogenous groups of congenital conditions characterized by atypical development of genetic,... (Review)
Review
Disorders/differences of sex development (DSDs) are defined as broad, heterogenous groups of congenital conditions characterized by atypical development of genetic, gonadal, or phenotypic sex accompanied by abnormal development of internal and/or external genitalia. gene mutation is one of the principal genetic alterations implicated in causing DSD. This review outlines the role of gene during the process of gonadal development in humans, provides an overview of the molecular and functional characteristics of gene, and discusses potential clinical phenotypes and additional organ diseases due to mutations. mutations were analyzed in patients with 46,XY DSD and 46,XX DSD both during the neonatal and pubertal periods. Loss of function of the gene causes several different phenotypes, including some associated with disease in additional organs. Clinical phenotypes may vary, even among patients carrying the same variant, indicating that there is no specific genotype-phenotype correlation. Genetic tests are crucial diagnostic tools that should be used early in the diagnostic pathway, as early as the neonatal period, when gonadal dysgenesis is the main manifestation of mutation. gene mutations could be mainly associated with amenorrhea, ovarian failure, hypogonadism, and infertility during puberty. Fertility preservation techniques should be considered as early as possible.
PubMed: 38785542
DOI: 10.3390/cimb46050274 -
Frontiers in Endocrinology 2024We present the evolution of GHD in adolescent males with persistent growth failure, in whom the diagnosis was established after a second GH stimulation test (GST).
INTRODUCTION
We present the evolution of GHD in adolescent males with persistent growth failure, in whom the diagnosis was established after a second GH stimulation test (GST).
METHODS
We performed a retrospective chart review of children who presented for short stature (height less < 2SD for mean/mid-parental height) and/or growth failure (sustained growth velocity < 0 SD) to pediatric endocrinology at Mount Sinai Kravis Children's Hospital, New York and who had 2 GSTs. Data collected from electronic medical records were analyzed using SPSS v28.0.
RESULTS
Of 53 patients included, 42 were males. Average GH peak on initial GST was 15.48 ± 4.92 ng/ml, at 10.07 ± 2.65 years, mean height -1.68 ± 0.56SD(28% had <2SD), IGF-1 -1.00 ± 0.88SD. After 2.23 ± 1.22 years, at 12.04 ± 2.41years, height SDs decreased to -1.82 ± 0.63SD and IGF-1 was -1.08 ± 0.84SD. At repeat GST, average GH peak was 7.59 ± 2.12 ng/dL, with 36% ≤7 ng/dl and 32% in puberty. 12 males reached adult height of 0.08 ± 0.69 SD with a mean height gain of 1.83 ± 0.56SD(p<0.005), IGF-1 of -1.15 ± 0.81SD after 4.64 ± 1.4 years of GH.
CONCLUSION
We offer evidence for Evolving Growth Hormone Deficiency (EGHD) through repeat GST in children with persistent growth slowdown, even with pubertal progression; emphasizing the need for careful longitudinal follow-up to make accurate diagnosis.
Topics: Humans; Male; Human Growth Hormone; Adolescent; Retrospective Studies; Child; Growth Disorders; Female; Body Height; Insulin-Like Growth Factor I; Proof of Concept Study; Dwarfism, Pituitary
PubMed: 38752175
DOI: 10.3389/fendo.2024.1398171 -
General and Comparative Endocrinology Aug 2024The reproductive failure of Senegalese sole (Solea senegalensis) cultured males (reared entirely in captivity from egg through to adult) that do not participate in...
The reproductive failure of Senegalese sole (Solea senegalensis) cultured males (reared entirely in captivity from egg through to adult) that do not participate in reproductive behaviours to fertilise spawns, results in a problem to achieve reproductive control in captivity. However, cohabitation with wild males has led to an increase in the involvement of cultured males in reproductive behaviour, although their contribution to fertilised spawning is still lower than that of wild breeders. This study aimed to examine the effect of different social conditions, on the reproductive behaviour and spawning success of cultured breeders over three reproductive seasons. Before starting this study, different social learning opportunities were provided to the breeders from the juvenile to the pubertal stages of the individuals. Behaviour and spawning were evaluated in four experimental groups of cultured breeders: two groups (W1 and W2) that prior to this study were reared during the juvenile stage with wild breeders that fertilized spawns, a Culture breeder group (CB) that was previously reared with cultured breeders that spawned unfertile eggs, and a negative control group (CN) that was reared in isolation from adult fish. During the three reproductive seasons, spawning was obtained from all groups. Generally, the first year had the highest egg production and the third year the lowest. However, fertilised eggs were only obtained from W1 in the first year. A total of eight fertilised spawns were collected with a fertilisation rate of 28.02 ± 13.80 % and a hatching rate of 15.04 ± 10.40 %. The mean number of larvae obtained per spawn was 7,683 ± 5,947 and the total number of larvae from all eight spawns was 61,468. The paternity analysis assigned 64.3 % of larvae to a single couple of breeders, while 34.3 % of larvae were not assigned to any single family, but inconclusively to more than three parents. The highest locomotor activity was observed in W1, while no significant differences were observed in the number of movements within W2, CB and CN. In all groups, during the peak of locomotor activity (19h00-20h00), the main reproductive behaviours observed were Rest the Head and Follow, while the Guardian behaviour was low and Coupled behaviour was only observed in W1. Over time, the reproductive behaviours decreased, except for Follow. The social learning opportunities provided by cohabitation with wild fish during juvenile stages prior to spawning in W1, increased activity and fertilised spawning. However, the number of successful spawns was low and over time stopped in association with a decrease in reproductive behaviour. This suggests that other mechanisms of behavioural learning could be involved in reproductive success, such as reproductive dominance, environmental conditions or hormonal interactions that could affect physiological processes in the reproduction of captive breeders.
Topics: Animals; Male; Flatfishes; Reproduction; Female; Reproductive Behavior
PubMed: 38719062
DOI: 10.1016/j.ygcen.2024.114546