Reproductive Activity Research Articles

Genome-Wide Structural Variation Analysis and Breed Comparison of Local Domestic Ducks in Shandong Province, China

Structural variations in the duck genome significantly impact the environmental adaptability and phenotypic diversity of duck populations. Characterizing these SVs in local domestic duck breeds from Shandong province offers valuable insights for breed selection and the development of new breeds. This study aimed to profile the genomic SVs in three local duck breeds (Matahu duck, Weishan partridge duck, and Wendeng black duck) and explore their differential distributions. A total of 21,673 SVs were detected using LUMPY (v0.2.13) and DELLY (v1.0.3) software, with 46% located in intergenic regions, 33% in intronic regions, and frameshift deletions being the most prevalent in exonic regions (3%). SVs distribution showed a decreasing trend with shorter chromosome lengths. Population structure analysis revealed distinct genetic profiles, with Matahu and Weishan partridge ducks showing closer affinities and the Wendeng black duck having a more homogeneous genetic background, likely due to geographic isolation. Functional annotation identified genes related to nervous system development, mitosis, spindle assembly, and energy metabolism. Notable genes included PLXNA4, NRP2, SEMA3A, PTEN, MYBL2, ADK, and COX4I1. Additionally, genes such as PRKG1, GABRA2, and FSHR were linked to energy metabolism and reproductive activity. The study provides a comprehensive analysis of SVs, revealing significant genetic differentiation and identifying genes associated with economically important traits, offering valuable resources for the genetic improvement and breeding of local duck breeds.

Juvenile hormone regulates reproductive diapause through both canonical and noncanonical pathways in the bean bug Riptortus pedestris

Diapause is an adaptive developmental arrest commonly utilized by animals to cope with seasonal changes. Central to this process are hormonal events that bridge photoperiodic cues and physiological changes. In insect reproductive diapause, the absence of juvenile hormone (JH) serves as the primary endocrine event that governs key diapause traits, including ovarian developmental arrest and lipid accumulation. Conventionally, it is believed that the effects of JH are conveyed through the receptor Methoprene-tolerant (Met) and its transcriptional factor Krüppel homolog 1 (Kr-h1). However, our study with the bean bug Riptortus pedestris reveals that JH independently regulates lipid accumulation, bypassing Met and Kr-h1 pathways. R. pedestris enters reproduction under long-day (LD) conditions, while diapause occurs under short-day (SD) conditions. Treatment of SD females with the JH mimic methoprene stimulated reproductive activities, enhancing ovary development and reducing lipid accumulation. In contrast, silencing genes essential for JH biosynthesis in LD females led to pronounced diapause characteristics, including ovarian developmental arrest and substantial lipid accumulation. Interestingly, disruptions in the JH action genes, either Met or Kr-h1, solely affected ovary development, leaving lipid accumulation unchanged, indicating an independent pathway for regulating JH in lipid accumulation. This was further confirmed by RNA interference experiments in SD females, where knockdown of Met or Kr-h1 did not alter the effects of methoprene on lipid reduction. Collectively, these results suggest that JH controls ovary development through the established Met-Kr-h1 pathway, while it modulates lipid accumulation through an alternative, yet to be identified noncanonical pathway during reproductive diapause in R. pedestris.

EFEKTIVITAS PELATIHAN PROGRAM GENRE TERHADAP KETERAMPILAN SEBAGAI PENDIDIK SEBAYA PADA REMAJA DI KABUPATEN JEMBER

Teenage behavior has changed a lot along with changing times and technological developments. These changes are more likely to be in a negative direction. Based on conditions like these, teenagers need information about reproductive health and useful activities, which is why the role of Peer Educators (PS) is needed. Method used in this research is the simplest pre-experimental and does not have a control group, with a One-shot Case Study Research Design approach, with a sample size of 62 Peer Educators. This research was conducted in June 2024, using the Peer Educator Achievement Indicator Checklist instrument. Data analysis used Paired T-Test with a value of α = 0.05. The results of the research show that before the training using the social skills training module method the average score was 72.43 and after being trained using the social skills training module method it was 83.83. The effectiveness of the GenRe training program using the social skills training module method on the skills of Peer Educators obtained a p value of 0.000. The conclusion from this research is the GenRe Training Program is effective in improving the skills of Peer Educators (PE). GenRe program training can be carried out on an ongoing basis to improve the skills of Peer Educators in providing education to their peers.

Evaluation of salivary total antioxidant capacity and malondialdehyde in pre-menopausal and post-menopausal women

Menopause is a natural and expected stage of development that occurs in the life of a woman and is characterized by the permanent end of menstruation. Ovarian dysfunction is a result of permanent alterations to the ovaries’ reproductive and hormonal activities. The reproductive system of a woman is not the only thing that is impacted by fluctuations in hormone levels. Hormones have powerful influence on the development of the skeleton and the mouth cavity, as well as on the integrity of these structures. The oral cavity is significantly affected by them. Different stages of a woman’s life, such as puberty, menstruation, pregnancy, and menopause, each have their own unique impact on the oral health. Oxidative stress is a condition that occurs when there is an imbalance between oxidants and antioxidants, with the former making it possible for living cells to sustain damage. Lipid peroxidation and the subsequent breakdown products, such as malondialdehyde (MDA), are formed, and these compounds can be observed in biological fluids. Total antioxidant capacity is a term that is frequently used to refer to the antioxidant activity of the “nonspecific” antioxidant pool.The objective: to assess of salivary total antioxidant capacity, salivary malondialdehyde, salivary pH in pre-menopausal and post-menopausal women and correlation between pH and salivary biomarkers. Materials and methods. A case-control study was conducted in 80 healthy women. The study included 80 females between the ages of 40 and 55 years; specifically, 40 persons were premenopausal and 40 women were postmenopausal.In the saliva of the patients, the total antioxidant capacity (TAC) and MDA level were determined using the immunoassay method, and the pH level was also studied. Data description, analysis and presentation were performed using Statistical Package for social Science (SPSS version 22, Chicago, Illinois, USA). Results. The findings indicated that the pH value in the post-menopausal group was significantly higher than that of the pre-menopausal group. In comparison to the post-menopausal group, the pre-menopausal group exhibited a significantly higher level of TAC. While MDA level was significantly greater in the post-menopausal group than in the pre-menopausal group. A significant correlation of salivary pH with biomarkers of TAC and MDA of saliva was found, but there was no significant correlation between MDA and TAC in premenopausal women. On the other hand, there is a non-significant negative correlation between salivary TAC and pH level, as well as an insignificant correlation of MDA with pH and salivary TAC in postmenopausal patients. Conclusions. There are differences in salivary total antioxidant capacity and malondialdehyde level between pre-menopausal and post-menopausal women.

Assessing the Viability of Translocated Mongolian Dung Beetles (Gymnopleurus mopsus) for Ecological Restoration in Republic of Korea: An Analysis of Environmental Adaptability

This study investigates the reintroduction and ecological adaptation of the endangered dung beetle, Gymnopleurus mopsus, in South Korea, a region from which it has been absent since the 1970s. To facilitate this, we imported genetically identical populations of G. mopsus from Mongolia and embarked on a comprehensive restoration research project. A key focus of this endeavor was to evaluate the adaptability of these beetles to the local environment, an essential aspect of successful reintegration of species from foreign ecosystems. Under meticulously controlled field cage conditions, we conducted an in-depth monitoring of the life history traits of G. mopsus. This monitoring revealed that the adult beetles, which entered hibernation in September 2019, began emerging in stages from late April to May 2020. Following hibernation, we observed that the adults engaged in reproductive activities from late-May until early-August, with the emergence of the first-generation (F1) adults occurring from late-July to mid-September. This led to a notable tripling in population size, increasing from 34 to 109 individuals. The successful survival and reproductive behaviors of these Mongolian dung beetles in the climatic conditions of Korea suggest a promising potential for their adaptation when reintroduced into native habitats. We are now directing our efforts towards long-term monitoring, focusing on the survival and reproductive efficacy of these new generations, to further validate the success of this ecological restoration project.

Role of Neurotransmitters (Biomediators) in Plant Responses to Stress.

Plants possess a complex signaling system that enables them to sense and adapt to various environmental stressors, including abiotic factors like extreme temperatures, drought, salinity, and toxic heavy metals. While the roles of hormones and signaling molecules in plant stress responses are well established, the involvement of neurotransmitters-traditionally linked to animal nervous systems-in plant stress physiology is a relatively underexplored area. Recent findings indicate that neurotransmitters such as gamma-aminobutyric acid, glutamate, serotonin, and dopamine play crucial roles in several physiological processes within plants. They regulate ion channels, adjust stomatal movements, modulate the production of reactive oxygen species, and influence gene expression. Evidence suggests that these neurotransmitters enhance antioxidant defense mechanisms and regulate stress-responsive pathways vital for plant stress tolerance. Additionally, under stressful conditions, neurotransmitters have been shown to impact plant growth, development, and reproductive activities. This review aims to illuminate the emerging understanding of neurotransmitters as key biomediators in plant responses to abiotic stress.

Potential of accelerometer tags for monitoring of Japanese quail (Coturnix japonica) reproductive behaviour

ABSTRACT 1. Monitoring behavioural dynamics in complex animal environments, such as poultry breeding facilities, poses a challenge. Utilising technological approaches, such as accelerometers, offers a solution to assess long-term changes in reproductive activity at an individual bird level. Specifically, these sensors measure acceleration associated with the position and movements of the body over time. However, it is important to assess the most suitable method for attaching accelerometer tags to ensure they do not negatively impact behaviour and yield high-quality data. 2. The potential of tri-axial accelerometer tags for assessing reproductive behaviour in Japanese quail was evaluated. Two attachment methods – a backpack (plastic platform with elastic bands near wing bases) and a patch (accelerometer on fabric glued to the synsacrum region) – were compared. Controls were handled similarly but without tags. Eighteen pairs of females were housed in pens and assessed immediately and 24 h after handling. After a week of habituation, a male from the same treatment group was introduced into each pen on d 8. The reproductive behaviour of the males was recorded using accelerometers and video recordings. 3. The results showed that birds with patches were able to remove their conspecific’s accelerometer and displayed an increased initial immobility response compared to the control and backpack groups. The presence of accelerometer tags did not impact male/female reproductive interactions nor fear responses to a novel object. From accelerometer recordings, male reproductive behaviour was easily identified as high amplitude fluctuations in the three axial components of the acceleration vectors, which was reflected as large values of dynamic body acceleration (VeDBA). 4. In conclusion, the use of backpacks with accelerometers is a useful strategy to address highly relevant and difficult to tackle behavioural topics such as the temporal dynamic of male reproductive behaviour within breeding groups.

Interaction between imidacloprid residues in maize rhizospheric soil and soil nematode community

Although imidacloprid has been shown to present potential risks to non-target invertebrates and vertebrates, researches exploring this risk from the perspective of the underground ecosystem remains incomplete. In this study, we determined that the presence of imidacloprid significantly reduced the abundance and diversity of soil nematodes in maize rhizospheric soil. Furthermore, imidacloprid also exerted negative effects on the body length, reproduction, locomotion, lipid accumulation, lipofuscin accumulation, and acetylcholinesterase activity in the model organism Caenorhabditis elegans. These toxic phenotypes are correlated with the upregulation of fat-2, fat-6, hsp-16.41, and hsp-16.2, along with the downregulation of ace-1, ace-2, and ace-3. In response to these toxic effects of imidacloprid, nematodes also developed corresponding adaptive mechanisms. UPLC-MS/MS analysis revealed that nematodes could convert imidacloprid to imidacloprid-guanidine and imidacloprid-urea to reduce the toxicity of imidacloprid. Moreover, C. elegans and Meloidogyne incognita exhibited repellent behavior towards imidacloprid-treated area, even the concentration of imidacloprid is only 0.4 μg/mL. This study revealed the interaction between imidacloprid and nematodes, providing a basis for understanding the potential risks of non-target soil nematodes after application of imidacloprid in sustainable agriculture and the resistance mechanism of nematodes to nematocidal pesticide.

Local agro-industrial by-products offer feasible options to supplement breeding rams in mixed farming systems of Ethiopia

This study assessed the supplemental effect of flushing Menz breeding rams with local agro-industrial by-products on their reproductive performance and semen quality. In a completely randomized design, rams (n=49) with an initial weight of 25.69+2.8 kg and average age of 18.79±3.9 months were allocated to seven treatments with seven replicates. Supplementation consisted of varying combinations of metabolizable energy (7.02, 8.14, 9.91 MJ ME/kg DM) and crude protein (CP) (8.17 and 12.5%) levels above the basal diet (pasture grazing). The experimental treatments were control, T0 (8 hours of free grazing in natural pasture and fallow lands providing 4.7 MJ/Kg metabolizable energy and 6.65 CP) supplemented with T1 (500g oats grain), T2 (500g maize bran), T3 (500g wheat bran), T4 (300g oat grain +150g broken lentil grain), T5 (300g maize bran + 150g broken lentil grain), T6 (400 g wheat bran). Supplementation significantly (P<0.05) improve body condition score, scrotal circumference, semen ejaculation volume, spermatozoa concentration, and predictive potential of rams to serve ewes. Notably, all variables within the supplemented groups showed no significant differences (P>0.05), except for scrotal circumference, where T1 and T3 showed a greater increase (P<0.05) compared to other treatments. High and positive correlations (r=0.89) between scrotal circumference and volume of semen were observed. Semen volume and concentration correlated positively (r=0.7 and r=0.9 respectively) with the rams’ potential to serve ewes. It is concluded that the reproductive activity of Menz rams is influenced by their nutritional state. Agro-industrial by-products can supply adequate protein and energy levels to enhance reproductive potential of rams. The studied agro-industrial by-products are relatively inexpensive and easily accessible compared to commercial concentrates. Hence, based on the cost-effectiveness of supplementary feed used; it is recommended that T3 and T6 wheat bran-based supplementation strategies be employed to enhance the reproductive performance, semen quality, and the potential of Menz rams to serve ewes. Further research is needed to evaluate how different seasons affect the levels of protein and energy supplementation required for ram flushing.

Sexual activity and climatic adaptation assessment of West African Dwarf goats introduced into Algeria

This study aimed to highlight the effects of variations in age, seasons and climatic conditions on the reproductive activity of West African Dwarf Goats imported from tropical zones in Algeria, and to verify the degree of their adaptation to Mediterranean climatic conditions. For this purpose, testicular biometry and hormonal analysis (testosterone and LH levels) using the radioimmunological method were carried out monthly. In total, seven goats aged between 18 to 48+ months were surveyed during the period from September 2021 to March 2022. The results showed a considerable effect of age on testicular measurements. Bucks less than 18 months recorded the lowest average testicular length, width, thickness and volume, scrotal width and circumference, as levels of testosterone concentrations. All variables were strong correlated. Seasonal variations in the average testicular measurements and hormonal concentrations were observed, without affecting testicular activity. Apart from thenegative action of ambient temperature, no effects of relative humidity or atmospheric pressure were revealed. West African Dwarf Goats showed a good capacity to adapt to Mediterranean climatic conditions through their continuous testicular activity during the year.

Comparative study of the reproductive activity of Calliptamus barbarus (Costa, 1839) and Calliptamus wattenwylianus (Pantel, 1836) in a subhumid bioclimatic region

The reproductive activity of Calliptamus barbarus and Calliptamus wattenwylianus was investigated to understand population dynamics and reproductive potential in a subhumid bioclimatic zone. Specimens were collected from July to October and dissected to assess ovarian development and egg-laying activity. The number of ovarioles, determined at birth, ranged from 62 to 67 for C. wattenwylianus and 48 to 58 for C. barbarus. Higher fertility was observed in C. wattenwylianus, with egg production increasing during the first oviposition for both species. The average reproductive yield was notable for C. barbarus (85.99%) and C. wattenwylianus (86.56%). Oocyte resorption occurred mainly during drought (August-September) and cold periods (October-November). C. wattenwylianus females reached maturity earlier, beginning in August, compared to C. barbarus. Egg production began in July for C. wattenwylianus and in September for C. barbarus. Oocyte retention rates were 5% for C. barbarus and 9% for C. wattenwylianus. These findings provide insights into reproductive patterns in North African Orthoptera, with implications for pest control in subhumid regions.

STRAIN SELECTION AND CULTIVATION OF FOOT-AND-MOUTH DISEASE VIRUSES FOR THE DEVELOPMENT OF A TRIVALENT INACTIVATED VACCINE

Foot-and-mouth disease is a well-known transboundary animal disease and has been recognised as a priority disease by the Steering Committee of the Global Framework for the Progressive Control of Transboundary Animal Diseases in Europe. The territory of the Republic of Kazakhstan is generally free of foot-and-mouth disease, however, sporadic cases of foot-and-mouth disease occur in various regions of the country as a result of importation from unfavorable countries. Epizootic safety in the Republic of Kazakhstan is maintained by vaccinating animals in the border areas of the southern and eastern regions. Inactivated vaccines against serotypes A, O, Asia produced by the All-Russian Research Institute of Animal Health (Russia) are used for vaccination. Continuous seromonitoring is carried out to maintain the level of post-vaccination antibodies at a high level, ensuring the immunity of animals to foot-and-mouth disease. However, despite all the measures taken, sporadic outbreaks of foot-and-mouth disease cause damage to livestock farming in the Republic of Kazakhstan. The effectiveness of preventive measures using vaccination depends on the strain used in the vaccine. The closer the strain used in the vaccine is genetically to the viruses circulating in that area, the more effective the preventive measures will be and the research conducted to create the most immunogenic domestic anti-foot-and-mouth disease vaccines have scientific and practical significance. This article presents the results of the selection of foot-and-mouth disease virus strains previously circulating in the territory of the Republic of Kazakhstan and studies their cultural and biological properties. Studies of the above-mentioned strains on adaptation to a transplantable cell culture line were conducted, the stability of cultural properties was studied over 10 generations and the stability was confirmed by the PCR method. Also, based on the studies, it was found that the maximum accumulation of the virus in cell culture occurs at a multiplicity of infection of 0.01-0.1 TCID50/cell. The reproductive activity of the studied isolates was within 6.5-7.25 lg TCID50/cm3 when cultivated for 16 hours.

Diet acts on sexual behavior development in a male moth.

In many animals, drastic changes are observed during sexual maturation characterized by the reproductive system development concomitantly to the sexual behavior ontogenesis. These modifications are under the control of internal and external factors such as food. Sexual maturation requires considerable energetic investment, and diet has been shown to affect reproductive activities in many taxonomic groups, especially in insects and vertebrates. By contrast, diet effects on sexual behavior development remain largely unexplored. To elucidate this aspect, we used the male moth Agrotis ipsilon which undergoes sexual maturation occurring between the third and the fifth day postemergence. During this period, males are sensitive to female sex pheromones and a stereotypical sexual behavior characterized by female-oriented flight takes place. In our study, we compared (1) sex pheromone detection by electroantennography recordings and (2) behavioral response in wind tunnel assays between males fed with different diets found in nature. Compared to standard sucrose diet, males fed with sucrose, fructose, and glucose supplemented with sodium (a mineral element necessary for the locomotor activity in several moths) did not respond better to female sex pheromones but clearly exhibited an earlier behavioral response. Thus, such a diet accelerates the development of sex pheromone-mediated oriented flight, probably by facilitating the central processing of sex pheromone information in male A. ipsilon moths. Our results provide new information on the influence of nutritional intake on the ontogenesis of male sexual behavior in animals.

Reproduction Activity of an Epigeic Earthworm Species (Dendrobaena octaedra) as Affected by a Complex of Environmental Factors

Reproduction Activity of an Epigeic Earthworm Species (Dendrobaena octaedra) as Affected by a Complex of Environmental Factors

Extreme population densities reduce reproductive effort of Atlantic sea scallops in high-density recruitment events

The Atlantic sea scallop Placopecten magellanicus supports one of the most valuable federal fisheries in the USA, with annual ex-vessel values of US$400-600 million since 2010. Among other strategies, the fishery utilizes rotational area management to protect juvenile sea scallops, increasing yield per recruit and spawning potential. While generally successful, area management was challenged by 2 extremely high-density recruitment events. Juveniles at both study sites, the Nantucket Lightship Closed Area and the Elephant Trunk portion of the Mid-Atlantic Access Area, persisted at high densities (up to 39 and 5 sea scallops m-2, respectively) and initially exhibited poor growth, yield, and gamete production. The effect of sea scallop population density on reproduction was investigated through quarterly sampling from May 2018 through January 2020 in low-, medium-, and high-density strata. Reproductive effort, i.e. the proportion of energy devoted to gamete production, was quantified to investigate differences in energy allocation across density, depth, shell height, reproductive stage, and sex. Reproductive activity was limited in the Nantucket Lightship high-density stratum, where the percentage of sea scallops staged as mature or spawning reached 50% during only 1 of 7 sampling trips, compared to 4-6 sampling trips in other strata. Population density was a significant predictor of reproductive effort, with a 28% reduction in reproductive effort from the highest densities to more typical densities. These results illustrate the complexities of managing fisheries for heterogeneous populations of sessile benthic invertebrates. Negative density-dependent effects should be monitored and accounted for in future extreme recruitment events.

Sex-specific expression of circadian rhythms enables allochronic speciation

Abstract Noctuid moths provide prime examples of species in various stages of allochronic speciation, where reproductive barriers are mediated by genetic divergence in daily or seasonal timing. Theory indicates that allochronic divergence might be one of the most plausible mechanisms of adaptive speciation, especially when timing is subject to divergent ecological selection. Here, we show that the validity of this theoretical expectation is entirely contingent on species characteristics of the mating system. Our analysis focuses on the moth Spodoptera frugiperda (Lepidoptera, Noctuidae), which occurs as two strains that differ in circadian reproductive activity. Unlike in generic models of assortative mating, where chronotypes diverge under mild assumptions, individual-based evolutionary simulations of the mating system and life cycle of S. frugiperda fail to recover allochronic diversification, even under conditions highly conducive to speciation. Instead, we observe that both chronotypes advance their activity schedule toward the early night, resulting in a rapid loss of allochronic variation. This outcome is caused by the fact that mating in S. frugiperda takes considerable time and potential mates are encountered sequentially, so that early males enjoy a systematic advantage. The undermining effect of male mate competition can be overcome when circadian genes evolve sex-specific expression, enabling early and late chronotypes to be maintained or even to diversify in sympatry. These results give new significance to sex differences in biological rhythms and suggest that species characteristics of the mating system and genetic architecture are key to understanding the scope for allochronic speciation across diverse species exhibiting variation in timing.

7788 Importance of Neuronal STAT3, but Not ERK2 or mTOR, for Pubertal Timing and Reproductive Activity in Mice

Abstract Disclosure: R.A. Lord: None. M.A. Inglis: None. G.M. Anderson: None. The adipose-derived hormone leptin is important for regulating reproduction. The canonical JAK2/STAT3 pathway is the best-characterised leptin receptor signalling pathway. Neural STAT3 deletion is known to cause obesity; however, its reproductive influence is less understood. This experiment investigated whether STAT3 knockout from brain neurons or AgRP neurons, a neuronal population necessary for normal pubertal timing and reproduction, would unveil the necessity of STAT3 in reproductive function. We also tested the role of ERK2 and mTOR, two alternative leptin signalling molecules.Transgenic mice with a neuronal knockout were created via the Cre-loxP system. CamKinaseIIα-Cre mice were crossed with STAT3, mTOR or ERK2 floxed mice. AgRP-Cre mice were crossed with STAT3 floxed mice for STAT3 knockout in AgRP neurons. All groups were compared to Cre-negative littermate controls (n=6-12/group). Puberty onset was assessed post-weaning by examining genitalia development. Reproductive cyclicity and organ weights were measured in adults. Metabolic effects were evaluated through body weight, abdominal fat and fasting glucose measurements. Brain tissue analysis evaluated cellular responses to leptin for STAT3, ERK2, and mTOR. Data presented as mean ± SEM.Mice with ERK2 KO or mTOR KO showed no reproductive or metabolic deficits compared to controls. In marked contrast, neuronal STAT3 KO mice showed significantly increased body weight by 5 weeks of age and a 6-fold increase in abdominal adiposity as adults (both p&amp;lt;0.001 using two-way ANOVA and Student’s t-test respectively) compared to controls. Males had a significant 5-day delay in age at preputial separation (KO: 32.1±2.09 d; Control: 26.8±0.45 d, p&amp;lt;0.01, Student’s t-test) while females had a significant 7-day delay in vaginal opening (KO: 33.0±1.85 d, Control: 26.6±0.37 d, p&amp;lt;0.05, Student’s t-test), a 9-day delay in first estrus (KO: 37.8±1.89 d; Control: 29.4±0.65 d, p&amp;lt;0.01, Student’s t-test) and pronounced acyclicity. Neuronal STAT3 KO mice also had a &amp;gt;2-fold elevation in fasting glucose levels (p&amp;lt;0.001, Student’s t-test) and regressed reproductive organs. Female mice with STAT3 knockout in AgRP neurons showed significantly increased body weight (by 3 weeks [p&amp;lt;0.001], two-way ANOVA) and a significant 3-day delay in first estrus (KO: 31.1±0.71 d, Control: 28.6±0.45 d, p&amp;lt;0.01, Student’s t-test). These data show that neuronal STAT3 is critical for correctly timed puberty and subsequent fertility in male and female mice, whereas mTOR and ERK2 are not essential. These results have prompted a re-evaluation of previous conclusions about the role of STAT3 from experiments using LepR-Cre mice. Additionally, AgRP neuronal requirements for STAT3 exactly recapitulate AgRP requirements for leptin receptors. A better grasp of leptin signalling pathways will improve our understanding of how infertility arises due to metabolic disease. Presentation: 6/3/2024

Role of gonadal hormones on brain sexualisation

It is now definitively established that the differentiation that leads to sexual dimorphism is not limited to the genital area but affects the entire individual. In particular, while knowledge of the dimorphism of the cerebral pole concerning the hypothalamic-pituitary-gonadal axis, which subtends, in its vast complex, functions and behaviours connected with reproductive activity, has become fairly clear thanks to recent studies, nothing has yet been definitively established concerning the sexualisation of other cerebral areas and in particular of the neocortex, which represents the part of the brain particularly involved in cognitive activities.

7940 Is Urocortin 2 A Mediator Of Stress-induced Suppression Of The Luteinizing Hormone Surge?

Abstract Disclosure: H.F. Bell: None. R.A. Carrasco: None. M.J. Kreisman: None. R.B. McCosh: None. K.M. Breen Church: None. Stress is thought to be a contributing factor to the reduction of reproductive function and infertility observed in many different species. Although this is a well-documented phenomenon, the neural mechanisms mediating the suppression of reproductive neuroendocrine activity in response to stress are not yet fully understood. The paraventricular nucleus (PVN) of the hypothalamus is an integral part of the neural response to stress. The PVN initiates activation of Corticotropin Releasing Hormone (CRH) neurons and, in addition to CRH, the PVN contains a population of neurons expressing Urocortin 2 (UCN2), a CRH-like family member, with high affinity for CRH receptor 2. In females, stress has been shown to inhibit both the pulse and surge modes of Luteinizing Hormone (LH) secretion. We have preliminary evidence that kisspeptin neurons, controlling either type of LH secretion, contain CRH receptor 2. In this study we tested the sufficiency of UCN2 to disrupt the estradiol-induced LH surge. Female mice were ovariectomized and given a high estradiol treatment to induce a circadian-timed LH surge. Two days later, UCN2 or Vehicle was administered into the lateral ventricle via ICV injection on the morning of the expected surge (10 AM). Blood and brains were collected in the evening (6 PM), at the time of the expected surge. Whole blood from the tail tip was measured by LH ELISA and a surge was defined as &amp;gt; 0.5 ng/mL. A majority of saline-treated animals expressed an LH surge (8 of 9 females). In contrast, 0% of UCN2-treated animals surged (n=7), suggesting that UCN2 impaired the positive feedback response to estradiol. Additionally, immunohistochemistry was performed to observe colocalization of c-Fos within Kisspeptin neurons in the rostral periventricular region of the third ventricle (RP3V) which are responsible for surge generation. Lower Kisspeptin/C-Fos co-expression in animals treated with UCN2 demonstrated the efficacy of UCN2 to impair estradiol-induced activation of RP3V Kisspeptin neurons which are critical for LH surge generation. These results support the hypothesis that UCN2 signaling plays a mediatory role in the stress-induced reduction of ovulatory function in the female mouse. Presentation: 6/1/2024

6846 Rare Variants in SEMA3A in Individuals with Constitutional Delay of Puberty (CDP)

Abstract Disclosure: W. He: None. E.C. Schafer: None. R. Brauner: None. A. Delaney: None. L. Dunkel: None. R. Grinspon: None. J.E. Hall: None. J.N. Hirschhorn: None. S. Howard: None. A. Latronico: None. A.A. Jorge: None. K. McElreavey: None. V. Mericq: None. P.M. Merino: None. M.R. Palmert: None. R.A. Rey: None. R.C. Rezende: None. S.B. Seminara: None. N. Shaw: None. T. Delayed Puberty Genetics Consortium: None. Y. Chan: None. Background: Constitutional delay of puberty (CDP), also known as self-limited delayed puberty, refers to late onset of puberty with relatively normal progression afterward. In contrast, idiopathic hypogonadotropic hypogonadism (IHH) results in a long-lasting defect in reproductive endocrine activity. Both CDP and IHH are highly heritable and are sometimes observed in different family members in the same pedigree. Previous work by our group and others has suggested genetic overlap between the two conditions. In this study, we aimed to identify specific IHH-related genes that are also genetic causes of CDP. Methods: The Delayed Puberty Consortium assembled exome data for 233 individuals of diverse ancestries with CDP, with onset of puberty between 12 and 18 y in girls and between 13.5 and 18 y in boys. For control data, we used exome sequencing data from gnomAD v2.1.1 (n=125,748). After data harmonization and quality control, we used a modification of the “TRAPD” method to perform gene-based burden testing for 63 genes associated with IHH. We analyzed rare variants (minor allele frequency &amp;lt; 0.01) with high impact (premature stop, frameshift, start-lost, stop-lost) in all individuals across ancestries (n=233), as allele frequencies for high-impact variants are unlikely to vary widely across populations. We also analyzed rare variants with moderate impact (missense, inframe insertions/deletions) predicted to be deleterious by the Primate AI algorithm (score &amp;gt;0.6) in non-Finnish European (NFE) individuals with CDP (n=99), then meta-analyzed the results for high- and moderate-impact variants. We considered p-values &amp;lt; 7.9 x 10-4 (0.05 with Bonferroni adjustment for 63 genes) significant. Results: Of the 63 genes analyzed, SEMA3A (which encodes semaphorin-3A) exhibited significant enrichment for moderate-impact variants in the NFE CDP cohort compared to controls (variant frequency in CDP vs control: 0.064 vs 0.0076, p = 1.3 x 10-4) and in the meta-analysis of both high- and moderate-impact variants (p = 3.5 x 10-6). Novel SEMA3A variants identified exclusively in CDP individuals but not in controls were a frameshift variant, p.F546fsX2, and a missense variant, I252R. Also, three missense variants in SEMA3A were observed at a higher frequency in NFE CDP individuals compared with controls: p.R66T, p.V461A, and p.T717I. No other IHH genes showed significant enrichment of rare variants in the CDP cohort. Conclusion: Rare variants in SEMA3A contribute to both CDP and IHH. While functional studies are required to assess the effects of these specific variants on protein function, previous in vitro studies of similar SEMA3A variants demonstrated defects in secretion or signaling activity. Subsequent studies employing individual-level ancestry-matched controls and larger CDP cohorts are planned to identify additional genes that contribute to CDP. Presentation: 6/1/2024