Reproductive developmental dynamics during the early and intermediate prepuberal periods in Nelore breed (Bos indicus) calves

The demand for calves as oocyte donors for in vitro embryo production is growing. However, Bos indicus have a late puberty, and some aspects of the reproductive physiology during the prepubertal period remain unclear. We characterized endocrine and morpho-functional reproductive features in Nelore calves (n=8) at 2- 5 (early prepubertal period, EPP) and from 8-11 months old (mo., intermediate prepubertal period, IPP). The calves’ ovaries and uterus were B-mode transrectal ultrasonography examined, and blood samples were collected every second week. The antral follicles number and size, and ovarian and uterine horn diameters, were recorded, and plasma FSH and LH concentrations were measured (RIA). Non-pregnant, non-lactating cyclic Nelore cows (n=8) were used as controls for endocrine endpoints. Somatic development was monitored by monthly weighing, and 3D scanning of the rump area. The somatic and endocrine endpoints were compared within and between EPP and IPP, and between each period and control cows. Associations were determined by the Spearman correlation method, and the developmental rates were determined by non-linear regression. All morphological endpoints, except antral follicle count, increased (P < 0.001) from the EPP to the IPP. However, within each period differences occurred only at EPP. During the EPP LH and FSH plasma concentrations were similar (P > 0.05), whereas during the IPP LH was lower (P < 0.05) and FSH was higher (P < 0.001) than control cows. The EPP calves showed moderate to high positive correlations among ovarian, uterine, and somatic endpoints. Conversely, the IPP such correlations were mostly weak. In summary, distinct ovarian activity and development patterns of primary and secondary sexual characteristics occurred in Nelore calves at 2- 5 mo compared to 8-11 mo.

The Role of Insulin-like Growth Factor-1 (IGF-1) in the Control of Neuroendocrine Regulation of Growth

In mammals, the neuroendocrine system, which includes the communication between the hypothalamus and the pituitary, plays a major role in controlling body growth and cellular metabolism. GH produced from the pituitary somatotroph is considered the master regulator of somatic development and involved, directly and indirectly, in carbohydrate and lipid metabolism via complex, yet well-defined, signaling pathways. GH production from the pituitary gland is primarily regulated by the counter-regulatory effects of the hypothalamic GHRH and SST hormones. The role of IGF-1 feedback regulation in GH production has been demonstrated by pharmacologic interventions and in genetically modified mouse models. In the present review, we discuss the role of IGF-1 in the regulation of the GH-axis as it controls somatic growth and metabolic homeostasis. We present genetically modified mouse models that maintain the integrity of the GH/GHRH-axis with the single exception of IGF-1 receptor (IGF-1R) deficiency in the hypothalamic GHRH neurons and somatotroph that reveals a novel mechanism controlling adipose tissues physiology and energy expenditure.

Being the Father of a Preterm-Born Child: Contemporary Research and Recommendations for NICU Staff

Background: Most studies on parental reactions to a preterm birth and to hospitalization of the newborn in Neonatal Intensive Care Units (NICUs) have involved mothers. However, emotional responses and behaviors of fathers are equally important. Usually, the father is the first to meet the preterm newborn, to find out information about baby's condition and to communicate to the mother and other family members. In this context he is often left alone and can show psychological difficulties including affective disorders such as depression or anxiety. This paper describes the role of fathers in the NICU, the best practices to support fathers, and to explain the role of a psychologist in the NICU staff. Considerations and suggestions are provided on the difficulties encountered to support parents, with a focus on the role of fathers during the COVID-19 pandemic.Methods and Discussion: Considering contemporary research data and following an attachment perspective, we analyze the role of the father of a preterm-born child in the relation with the partner and in newborn caring. Research has shown that involving fathers in newborn care in NICU and at home is essential not only because it promotes the father/son attachment relationship and has positive effects on the psychological and somatic development of the newborn, but also for the health of the mother and whole family.Conclusion: Recommendations are provided to enhance the functions of fathers in the NICU, promote their involvement in the care of their infant, and interventions to prevent the manifestation of psychological suffering and/or perinatal affective disorders. The commitments of a psychologist in a NICU team are presented and require not only clinical skills, but also the ability to manage the emotional and relational difficulties of fathers, family and NICU staff. Considerations and suggestions are provided on the difficulties encountered by parents in the NICU during the COVID-19 pandemic.

Dental Age in Precocious and Delayed Puberty Periods

Objectives Precocious puberty indicates quick growth inception and delayed puberty indicates retardation in growth. This study aims to investigate whether dental development is synchronous with somatic development. Materials and Methods In this study, 62 girls and 34 boys with precocious puberty aged 5 to 9, 29 girls with delayed puberty aged 13 to 16, and 43 boys with delayed puberty aged 14 to 17; 169 children (91 girls and 78 boys) with normal development were compared about their dental ages through their panoramic radiographs by using the Demirjian method and skeletal ages from hand-wrist radiographs by using Greulich-Pyle atlas. Results The findings showed that, in all cases, the dental age values were higher than chronologic and skeletal age values to a statistically significant degree. In the precocious puberty group, the dental age values were higher than chronologic age values to a statistically significant degree. In the delayed puberty group, the difference determined between the chronological age and the dental age was not found to be statistically significant. Conclusion Given that the Demirjian method is inclined to make calculations that are higher than the chronological age, our findings suggest that the dental development was faster in the precocious puberty group and retarded in the delayed puberty group.

Blastocyst complementation using Prdm14-deficient rats enables efficient germline transmission and generation of functional mouse spermatids in rats

Murine animal models from genetically modified pluripotent stem cells (PSCs) are essential for functional genomics and biomedical research, which require germline transmission for the establishment of colonies. However, the quality of PSCs, and donor-host cell competition in chimeras often present strong barriers for germline transmission. Here, we report efficient germline transmission of recalcitrant PSCs via blastocyst complementation, a method to compensate for missing tissues or organs in genetically modified animals via blastocyst injection of PSCs. We show that blastocysts from germline-deficient Prdm14 knockout rats provide a niche for the development of gametes originating entirely from the donor PSCs without any detriment to somatic development. We demonstrate the potential of this approach by creating PSC-derived Pax2/Pax8 double mutant anephric rats, and rescuing germline transmission of a PSC carrying a mouse artificial chromosome. Furthermore, we generate mouse PSC-derived functional spermatids in rats, which provides a proof-of-principle for the generation of xenogenic gametes in vivo. We believe this approach will become a useful system for generating PSC-derived germ cells in the future.

5 Heat stress during pregnancy compromises intrauterine development and reproductive parameters of female progeny in C57BL/6J mice

Heat stress (HS) affects the reproduction of many species, causing subfertility by reducing gametogenesis. This study assessed the effect of HS at different stages of pregnancy in C57BL/6J mice on the somatic development and reproductive parameters of F1 females. A total of 40 females and 40 males aged between 5 and 6 weeks old were mated (1:1). After mating confirmation (vaginal plug presence) the females were subjected to HS during pregnancy in the first half (FP, from Day 1 to 10; n=10), the second half (SP, from Day 11 to delivery; n=10), or the total pregnancy (TP, n=10). A control group (C, n=10) was maintained in normothermic conditions (25°C, 45% relative humidity) throughout the experiment. The HS was induced (41°C for 2h daily) in an environmental chamber heated by 2 red lamps. After delivery, birthweight was recorded and somatic development of the F1 females was monitored weekly until 8 weeks of age. They were superovulated with 5IU of equine chorionic gonadotrophin (eCG) and 5IU of human chorionic gonadotrophin (hCG) 48h later and mated with control F1 males in four groups: FP×C; SP×C; TP×C; and C×C, female and male, respectively. At 72h after mating confirmation, uterine flushing was performed with 0.5mL of phosphate-buffered saline + 0.4% bovine serum albumin and embryos classified. Ovaries were collected for histological analysis of the follicular population with the formula: follicles per ovary×n section×section thickness/n section observed×average diameter of the oocyte nucleus. Pregnancy rate was analysed by chi-squared test. Data of pups born per female, birthweight, somatic development, follicular population, total and viable structures recovered by female were tested for normality by the Shapiro-Wilk test, before ANOVA and Tukey test. Values of P&lt;0.05 were considered to indicate a difference and P&lt;0.10a tendency. No difference (P&gt;0.05) among groups was detected in pregnancy rate (C=80; FP=40; SP=60; TP=60%) or in the number of pups born per female (C=7.0±1.0; FP=6.0±1.5; SP=6.5±1.5; TP=5.1±1.5). Birthweight was lower (P&lt;0.05) for FP (1.1g) and TP (1.2g) than for C (2.2g) and SP (1.8g). However, this difference disappeared (P&gt;0.05) in the third week of development and remained similar until the eighth week (C=21.0; FP=20.4, SP=20.3, TP=20.0g). Similar (P&gt;0.05) follicular population by ovary (total, primordial, primary, secondary, and antral) was observed between the C and HS groups. However, among HS groups, the total number of follicles and number of primordial follicles, respectively, were lower (P&lt;0.05) in the FP (1623; 942) compared with SP (2735; 1918) and TP (2626; 2352); with no difference in primary, secondary, and antral follicles. This resulted in similar (P&gt;0.05) total number of structures recovered by females (C=11.8±5.0, FP=7.6±2.4, SP=10.8±5.5, TP=6.9±3.1), with a tendency (P=0.06) to fewer viable embryos in TP (4.3±2.7) compared with C (9.5±4.6). Considering the increasing global temperature, it is imperative to understand the effects of HS on animal reproductive capacity. In conclusion, gestational HS impaired mice intrauterine development and changed the ovarian follicular population in the F1 generation.

Somatic development in children with Shwachman-Diamond syndrome

Background Shwachman-Diamond syndrome (SDS) is a rare genetic, multi-systemic disease characterized by exocrine pancreatic insufficiency, immune deficiency, bone marrow failure and skeletal abnormalities. Most patients present with failure in somatic development and short stature, but systematic data concerning those features are limited. The aim of the study was to assess the prevalence of failure in somatic development in the children with SDS. Methods An analysis of anthropometric measurements of 21 patients (14 girls and 7 boys),aged 2 to 17 years (mean age 6.3 years) with SDS diagnosed in The Children’s Memorial Health Institute in Warsaw, Poland was performed. The patients were measured using a Holtain Limited stadiometer, an electronic scale, a Harpenden anthropometer, a metric tape and a spreading caliper. The assessed anthropometric parameters were expressed as standard deviation scores in relation to the reference values in Poland, suitable for sex as well as calendar and growth age. Results A total of 66 measurements was collected and analyzed with a median number of 3 observations per patient. The group of boys presented with a significantly lower height (− 3.0 SD, p < 0.0001) and BMI (− 1.4 SD, p < 0.00001), and in the relation to the growth age a lower weight (− 1.0 SD, p < 0.001) as well as a smaller chest width (− 0.9 SD, p < 0.05), hip width (− 0,5 SD, p < 0,05) and lower limb length (− 0,5 SD, p < 0,05). The group of girls also showed significantly lower height (− 2.6 SD, p < 0.00001) and BMI (− 0.8 SD, p < 0.00001), and in relation to the growth age, lower weight (− 0.5 SD, p < 0.001) as well as decreased width of the chest (− 1.7 SD, p < 0.0001) and shoulder (− 1.0 SD, p < 0.001) were observed. Boys and girls were also characterized by significantly decreased circumference and width of head, additionally, girls had also smaller head length. Conclusions Patients with SDS have abnormal somatic development. Both boys and girls are characterized by short stature, decreased weight, BMI, leg length, chest width as well as circumference and width of head. Anthropometric measurements provide important data on the process of growth and body proportions in children with SDS.

AlphaBeta: computational inference of epimutation rates and spectra from high-throughput DNA methylation data in plants

Stochastic changes in DNA methylation (i.e., spontaneous epimutations) contribute to methylome diversity in plants. Here, we describe AlphaBeta, a computational method for estimating the precise rate of such stochastic events using pedigree-based DNA methylation data as input. We demonstrate how AlphaBeta can be employed to study transgenerationally heritable epimutations in clonal or sexually derived mutation accumulation lines, as well as somatic epimutations in long-lived perennials. Application of our method to published and new data reveals that spontaneous epimutations accumulate neutrally at the genome-wide scale, originate mainly during somatic development and that they can be used as a molecular clock for age-dating trees.