Reduced Litter Size Research Articles

Maternal early overfeeding negatively impacts cardiac progenitor cells differentiation and cardiomyocyte maturation in the neonatal offspring.

Maternal obesity has been positively correlated with an increased cardiometabolic risk in the offspring throughout life, implying intergenerational transmission. However, little is known about the early life cardiac cell modifications that imply the onset of heart diseases later in life. This study analyzed cardiac progenitor cells and cardiomyocyte differentiation on day of birth in the offspring born to obese dams. The litter size reduction model was used to induce obesity in female Swiss mice. Both maternal groups, the Small Litter Dams (SLD-F1), which were overfed during lactation, and the Normal Litter Dams (NLD-F1), control group, were mated to healthy male mice. Their first generation offspring (SLD-F2 and NLD-F2, n=6 by group) were euthanized on birth. Mothers from SLD had increased body mass, Lee Index, fat deposits, hyperglycemia, and glucose intolerance, confirming the obese phenotype. The offspring born from SLD-F1 had also increased body mass, Lee Index, and fasting hyperglycemia. The heart of SLD-F2 showed decreased cardiac mass/body mass ratio, increased cardiac collagen deposits, and a greater number of undifferentiated cardiac c-kit+ and Sca-1+ progenitor cells, and increased NKX2.5+ cardiomyoblasts compared to control. In addition, SLD-F2 demonstrated immature cardiomyocytes. Obese dams negatively impact its offspring, leading to altered biometric and metabolic parameters, along with an immature heart already at birth, with extracellular matrix adverse remodeling, delayed cardiac progenitor cells differentiation and restrained cardiomyocyte maturation, which can be related with the development of cardiometabolic disease in the adulthood.

LH-stimulated periodic lincRNA HEOE regulates follicular dynamics and influences estrous cycle and fertility via miR-16-ZMAT3 and PGF2α in pigs

Disruption of the estrous cycle affects fertility and reproductive health. Follicular dynamics are key to the regularity of the estrous cycle. We identified a novel lincRNA, HEOE, showing significant upregulation in the ovaries during the estrus phase across various pig breeds. Functional analysis revealed that HEOE is responsive to luteinizing hormone (LH) stimulation, modulating transcriptional suppression and alternative splicing in ovarian granulosa cells (GCs). This leads to increased GC apoptosis and inhibition of proliferation. Mechanistically, HEOE inhibits miR-16 maturation in the nucleus, and sequesters miR-16 in the cytoplasm, thereby collectively reducing miR-16's inhibition on ZMAT3, enhancing the expression of ZMAT3, a key factor in the p53 pathway and alternative splicing, thereby regulating follicular development. This effect was validated in both mice and pig follicles. Persistent overexpression or suppression of HEOE throughout the estrous cycle impairs cycle regularity and reduces litter size. These outcomes are associated with HEOE reduced follicular PGF2α levels and modulation of the cAMP signaling pathway. Our data, combined with public databases, indicate that the high expression of HEOE during the estrus phase is crucial for maintaining the estrous cycle. HEOE is a potential therapeutic target for regulating fertility and ensuring estrous cycle regularity in pigs.

Postnatally overfed mice display cardiac function alteration following myocardial infarction

BackgroundCardiovascular (CV) pathologies remain a leading cause of death worldwide, often associated with common comorbidities such as overweight, obesity, type 2 diabetes or hypertension. An innovative mouse model of metabolic syndrome induced by postnatal overfeeding (PNOF) through litter size reduction after birth was developed experimentally. This study aimed to evaluate the impact of PNOF on cardiac remodelling and the development of heart failure following myocardial infarction. MethodsC57BL/6 male mice were raised in litter adjusted to 9 or 3 pups for normally-fed (NF) control and PNOF group respectively. After weaning, all mice had free access to standard diet and water. At 4 months, mice were subjected to myocardial infarction (MI). Echocardiographic follows-up were performed up to 6-months post-surgery and biomolecular analyses were carried-out after heart collection. FindingsAt 4 months, PNOF mice exhibited a significant increase in body weight, along with a basal reduction in left ventricular ejection fraction (LVEF) and an increase in left ventricular end-systolic area (LVESA), compared to NF mice. Following MI, PNOF mice demonstrated a significant decrease in stroke volume and an increased heart rate compared to their respective initial values, as well as a notable reduction in cardiac output 4-months after MI. After 6-months, left ventricle and lung masses, fibrosis staining, and mRNA expression were all similar in the NF-MI and PNOF-MI groups. InterpretationAfter MI, PNOF mice display signs of cardiac function worsening as evidenced by a decrease in cardiac output, which could indicate an early sign of heart failure decompensation.

The epithelial Na+ channel (ENaC) in ovarian granulosa cells modulates Ca2+ mobilization and gonadotrophin signaling for estrogen homeostasis and female fertility

Ovarian granulosa cells are essential to gonadotrophin-regulated estrogen production, female cycle maintenance and fertility. The epithelial Na+ channel (ENaC) is associated with female fertility; however, whether and how it plays a role in ovarian cell function(s) remained unexplored. Here, we report patch-clamp and Na+ imaging detection of ENaC expression and channel activity in both human and mouse ovarian granulosa cells, which are promoted by pituitary gonadotrophins, follicle stimulating hormone (FSH) or luteinizing hormone (LH). Cre-recombinase- and CRISPR-Cas9-based granulosa-specific knockout of ENaC α subunit (Scnn1a) in mice resulted in failed estrogen elevation at early estrus, reduced number of corpus luteum, abnormally extended estrus phase, reduced litter size and subfertility in adult female mice. Further analysis using technologies including RNA sequencing and Ca2+ imaging revealed that pharmacological inhibition, shRNA-based knockdown or the knockout of ENaC diminished spontaneous or stimulated Ca2+ oscillations, lowered the capacity of intracellular Ca2+ stores and impaired FSH/LH-stimulated transcriptome changes for estrogen production in mouse and/or human granulosa cells. Together, these results have revealed a previously undefined role of ENaC in modulating gonadotrophin signaling in granulosa cells for estrogen homeostasis and thus female fertility.

Conditional loss of Brca1 in oocytes causes reduced litter size, ovarian reserve depletion and impaired oocyte in vitro maturation with advanced reproductive age in mice

An estimated 1 in 350 women carry germline BRCA1/2 mutations, which confer an increased risk of developing breast and ovarian cancer, and may also contribute to subfertility. All mature, sex steroid-producing ovarian follicles are drawn from the pool of non-renewable primordial follicles, termed the 'ovarian reserve'. The clinical implications of early ovarian reserve exhaustion extend beyond infertility, to include the long-term adverse health consequences of loss of endocrine function and premature menopause. We aimed to determine whether conditional loss of Brca1 in oocytes impacts ovarian follicle numbers, oocyte quality and fertility in mice with advancing maternal age. We also aimed to determine the utility of AMH as a marker of ovarian function, by assessing circulating AMH levels in mice and women with BRCA1/2 mutations, and correlating this with ovarian follicle counts. In this study, we addressed a longstanding question in the field regarding the functional consequences of BRCA1 inactivation in oocytes. To recapitulate loss of BRCA1 protein function in oocytes, we generated mice with conditional gene deletion of Brca1 in oocytes using Gdf9-Cre recombinase (WT: Brca1fl/flGdf9+/+; cKO: Brca1fl/flGdf9cre/+). While the length of the fertile lifespan was not altered between groups after a comprehensive breeding trial, conditional loss of Brca1 in oocytes led to reduced litter size in female mice. Brca1 cKO animals had a reduced ovarian reserve and oocyte maturation was impaired with advanced maternal age at postnatal day (PN)300, compared to WT animals. Serum anti-Müllerian hormone (AMH) concentrations (the gold-standard indirect marker of the ovarian reserve used in clinical practice) were not predictive of reduced primordial follicle number in Brca1 cKO mice versus WT. Furthermore, we found no correlation between follicle number or density and serum AMH concentrations in matched samples from a small cohort of premenopausal women with BRCA1/2 mutations. Together, our data demonstrate that BRCA1 is a key regulator of oocyte number and quality in females and suggest that caution should be used in relying on AMH as a reliable marker of the ovarian reserve in this context. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. This work was supported by funding from the Australian Research Council (ALW - DE21010037 and KJH - FT190100265), as well as the National Breast Cancer Foundation (IIRS-22-092) awarded to ALW and KJH. LRA, YML, LT, EOKS and MG were supported by Australian Government Research Training Program Scholarships. LRA, YML and LT were also supported by a Monash Graduate Excellence Scholarship. YC, SG and XC were supported by Monash Biomedicine Discovery Institute PhD Scholarships. LRA was also supported by a Monash University ECPF24-6809920940 Fellowship. JMS was supported by NHMRC funding (2011299). MH was supported by an NHMRC Investigator Grant (1193838).

Transcription Factor 23 is an Essential Determinant of Murine Term Parturition.

Pregnancy involving intricate tissue transformations governed by the progesterone hormone (P4). P4 signaling via P4 receptors (PRs) is vital for endometrial receptivity, decidualization, myometrial quiescence, and labor initiation. This study explored the role of TCF23 as a downstream target of PR during pregnancy. TCF23 was found to be expressed in female reproductive organs, predominantly in uterine stromal and smooth muscle cells. Tcf23 expression was high during midgestation and was specifically regulated by P4, but not estrogen. The Tcf23 knockout (KO) mouse was generated and analyzed. Female KO mice aged 4-6 months exhibited subfertility, reduced litter size, and defective parturition. Uterine histology revealed disrupted myometrial structure, altered collagen organization, and disarrayed smooth muscle sheets at the conceptus sites of KO mice. RNA-Seq analysis of KO myometrium revealed dysregulation of genes associated with cell adhesion and extracellular matrix organization. TCF23 potentially modulates TCF12 activity to mediate cell-cell adhesion and matrix modulation in smooth muscle cells. Overall, TCF23 deficiency leads to impaired myometrial remodeling, causing parturition delay and fetal demise. This study sheds light on the critical role of TCF23 as a dowstream mediator of PR in uterine remodeling, reflecting the importance of cell-cell communication and matrix dynamics in myometrial activation and parturition.

Postnatal overfeeding in mice induces early lipidic changes in heart tissue and impacts cardiomyocyte proliferation

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): French Federation of Cardiology Foundation of France Background Shortly after birth, cardiomyocytes lose their ability to proliferate to switch towards a hypertrophic growth and this ability is known to be influenced by nutritional factors. Postnatal overfeeding (PNOF) induced by litter size reduction in rodents reproduces the impact of childhood overnutrition. While PNOF was shown to induce major cardiac and metabolic alterations in adulthood, little is known about its impact during the first days of life. Purpose The objective of this project was to investigate the early changes induced by PNOF induced in heart tissue in terms of lipid profile and cardiomyocyte proliferation. Methods Two days after birth, C57BL/6 male pups were randomly distributed in litters adjusted to either 9 or 3 pups to form normally fed (NF) or postnatally overfed (PNOF) group, respectively. At 7, 10 and 24 postnatal days (D7, D10 and D24, respectively), hearts were harvested for immunostaining of the proliferation marker Ki67. Cardiac and plasma lipid composition of NF and PNOF was evaluated using liquid chromatography coupled to mass spectrometry technique. Finally, cardiomyocytes from D24 hearts were isolated and counted on Malassez counting chamber. Results At D7, D10 and D24, body weight and cardiac mass of PNOF pups were significantly higher than these of NF controls. Interestingly, at D7, lipid composition of PNOF hearts was decreased in cardiolipins, fatty acids and cholesterol derivatives. Moreover, plasma triglyceride levels were lower in D10 PNOF pups. These modifications were associated with a significant reduction of cardiomyocytes’ proliferation rate and an increased hypertrophy in PNOF hearts at D7, resulting in the reduction of cardiomyocyte number at D24 in PNOF mice. Conclusion Only five days after litter size reduction, PNOF induced major lipidic changes both in the cardiac tissue and in the plasma. In parallel, PNOF shortened the cardiomyocyte proliferative window and induced earlier cardiomyocyte maturation. Given the importance of fatty acid metabolism in cardiac development and function, these early changes could be linked to the long-term cardiometabolic alterations observed later in life.

Long-term impact of postnatal nutritional programming on cardiac sensitivity to ischemia-reperfusion injury in vivo and on glucose metabolism

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Fondation de France Introduction Nutritional environment during intra uterine and postnatal period has a major impact on health and disease in adulthood. The early programming of cardiometabolic risk through a postnatal overfeeding in rodents leads to a permanent increase in body weight, associated with alteration of left ventricular contractility, higher cardiac sensitivty to ischemic or chemo-toxic stresses and alterations of glucose métabolism in adulthood. However, these data have mainly obtained in young rodents and less is known for older animals. Purpose Our aim was to evaluate the impact of postnatal overfeeding (PNOF) on cardiac function, on cardiac sensitivity to ischemia-reperfusion (I-R) injury in vivo, on glucose metabolism and on metabolic profile of pericardial adipose tissue (PAT) in young (4 months), adult (6 months) and old (12 months) male mice. Methods PNOF was induced by the reduction of litter size of C57/BL6 mice immediately after birth: normally-fed group (NF) was composed of 9 male pups/mother and overfed group (PNOF) of 3 pups/mother. Echocardiography and blood sugar tests (glucose tolerance and insulin resistance) were performed at all ages. An in vivo ischemia-reperfusion injury was induced by the ligation of the left anterior descending coronary artery for 45 minutes followed by 24 h of reperfusion. PAT was harvested and weighted, in order to investigate by rt-qPCR its inflammatory status. All experiments were performed in 4-, 6- and 12-months aged mice. Results PNOF induced an early and permanent increase in body weight in PNOF group, independently of mice’s age (+23% at 24 days of life, +14% at 4 months, +23% at 6 and 12 months, compared to NF group). Echocardiographic measurements showed an alteration of left ventricular ejection fraction in mice aged from 4 months up to 12 months (-11 % on average, compared to NF groups). PNOF mice presented glucose intolerance and insulin resistance from 4 to 12 months of age. Moreover, PNOF mice had a higher PAT mass indexed to body weight with increased inflammatory status and decreased activin A mRNA expression at 6 and 12 months. Finally, PNOF induced a significant increase of infarct size at 4 months (+37%, p<0.01, n=8), 6 months (+32%, p<0.05, n=9) and 12 months (+38%, p<0,05, n=9) after cardiac surgery. Conclusion Nutritional programming through short-term PNOF induced an early and permanent overweight, an increase in pericardial fat mass with a greater inflammatory status, associated with alterations of glucose metabolism, alteration of systolic function and a higher sensitivity to ischemia reperfusion injury induced in vivo. The cellular mechanisms of these pathological modifications induced by PNOF need further exploration but could involve alterations in cardiomyocyte pathways and/or modification of global inflammatory status. Therefore, the PNOF mice model corresponds to a relevant experimental model of programmed metabolic syndrome as we known in humans.

The mammalian sperm factor phospholipase C zeta is critical for early embryo division and pregnancy in humans and mice.

The mammalian sperm factor phospholipase C zeta is critical for early embryo division and pregnancy in humans and mice.

Effects of Elective Caesarean Sections in Healthy Near-Term Ewes on Subsequent Reproductive Performance.

Post-surgical reproductive performance following ovine caesarean section has not been well studied. To assess any direct effects of surgical delivery in the absence of confounders such as dystocia or underlying diseases, we studied elective surgery performed in healthy animals for teaching purposes. Four hundred and eleven paired breeding records following vaginal delivery (n = 233), elective caesarean section (n = 122), and subsequent further vaginal deliveries in animals with a history of one prior elective caesarean operation (n = 56) were evaluated retrospectively. The overall subsequent pregnancy rate was 95%. Multivariable statistical analyses did not reveal any significant influence of planned caesarean surgery on subsequent conception, stillbirth, perinatal lamb mortality, lamb birth weights, or the incidence of premature foetal death (mummification and abortion). A significantly higher number of mating attempts was, however, necessary. Also, a significant reduction in litter size was seen in the first pregnancy immediately following a surgical delivery in comparison to animals which had previously only delivered vaginally (p = 0.001), but litter size returned to pre-caesarean levels in further follow-up pregnancies in animals with a history of one elective caesarean section (p = 0.436). Subsequent long-term reproductive performance of sheep following elective caesarean section is thus excellent, and the results encourage retention for breeding.

EFECTO DEL TAMAÑO DE CAMADA EN PRIMER PARTO Y SEGUNDO PARTO SOBRE LA PRODUCTIVIDAD ACUMULADA DE LAS CERDAS, EN UNA GRANJA COMERCIAL DE YUCATÁN, MÉXICO

<p><strong>Background.</strong> Litter size reduction at second farrowing (RSP) affects cumulative productivity per productive life of sows. <strong>Objective.</strong> To compare groups of sows according to their classification by number of piglets born alive (LNV) at first farrowing and reduction or increase of LNV at second farrowing on the number of farrowings at culling (NPD), cumulative LNV and weaned per productive life of sows in a commercial farm in the eastern zone of Yucatan, Mexico. <strong>Methodology</strong>. Data from 404 culled sows were used. Six groups of sows were established: low number of LNV at first farrowing with RSP (B-RSP), low with increased number of LNV at second farrowing (B-ISP), medium with RSP (M-RSP), medium with ISP (M-ISP), high with RSP (A-RSP) and high with ISP (A-ISP). The response variables were NPD, cumulative piglets born alive during the productive life of the sows (LNVP) and cumulative piglets weaned during the productive life of the sows (LDVP). <strong>Results.</strong> No difference was found between the different sow groups for NPD and LDVP (P>0.05). The lowest number of LNVP was obtained in sows of groups B-RSP and B-ISP (P<0.05). <strong>Conclusion.</strong> Under the conditions of this study, NPD and LDVP of sows during their stay on the farm were not affected by RSP or ISP. LNVP was not affected by reduction or increase of piglets at second farrowing in sows with small litters at first farrowing.</p>

Impaired fertility in adenomyosis: a murine model reveals endometrial receptivity and progesterone resistance imbalances.

The impact of adenomyosis on reproductive health needs to be fully understood. By using a murine model, this study provides novel insights into the nuanced mechanisms associated with fertility challenges and offers a foundation for targeted interventions. This study investigates the intricate relationship between adenomyosis and reproductive health using a murine model, offering novel insights into this prevalent gynecological disorder. Adenomyosis, characterized by the invasive growth of endometrial tissue into the myometrium, is believed to negatively impact fertility. However, the challenge lies in disentangling this influence, as adenomyosis often coexists with other gynecological diseases. A tamoxifen-induced mice model presents a significant advantage by enabling the specific study of adenomyosis, devoid of confounding influences of concurrent gynecological diseases such as endometriosis. Focusing exclusively on adenomyosis, our study aims to elucidate pathogenic mechanisms underlying fertility issues, focusing on estrous cyclicity, ovarian follicle development, and overall fertility. Our findings uncover disruptions in estrous cyclicity, characterized by an increased duration of time spent in the estrus phase in adenomyosis-induced mice. These disturbances are potentially linked to observed compromised folliculogenesis and the remarkable reduction in litter number and size in mice affected by adenomyosis. Moreover, this study unveils potential drivers of subfertility such as progesterone resistance and altered endometrial receptivity. Within the uteri of mice with adenomyosis, reduced expression of the progesterone receptor and a decreased expression of two implantation-related markers (HoxA10 and integrin β3) were observed. This comprehensive examination sheds light on the nuanced complexities of adenomyosis-associated reproductive challenges, providing a foundation for targeted interventions in addressing fertility issues related to this disease.

Heterothermy use in winter is associated with reduced litter size during following breeding season

Heterothermy is considered to be the most effective energy-saving strategy improving survival under natural conditions. Interspecific studies suggest that this strategy is also associated with reduced reproductive output. Yet little is known about the reproductive consequences of heterothermy use at the intraspecific level and thus its repercussions for microevolutionary processes. Moreover, as yet no study has aimed to test if litter size and juvenile mass are affected by torpor use in wild captured animals under undemanding laboratory conditions. Here we tested the hypothesis that intraspecific variation in heterothermy use is associated with different reproductive successes, being the result of the evolution of distinct life histories. We predicted that heterothermy use in winter negatively correlates with litter size and juvenile body mass during the subsequent breeding season. To test this prediction, we used yellow-necked mice from a population in which individuals consistently differ in their use of heterothermy in winter. We measured body size (head width) and body mass, basal metabolic rate, as well as metabolism and body temperature during fasting-induced torpor in wild caught mice in winter. Phenotyped mice were bred in the subsequent summer selectively – males and females with similar heterothermy characteristics were paired, the most to the least heterothermic. Dam body size, but not basal metabolism, was positively correlated with litter size (but not juvenile mass). However, when accounting for this relationship, litter size was negatively while juvenile mass was positively correlated with the average heterothermy use of a given couple. Our study indicates that heterothermy use correlates with specific life-history strategies arising from a fundamental evolutionary trade-off between survival and reproduction.

Disruption of the SP-A/SP-R210L (MYO18Aα) pathway prolongs gestation and reduces fetal survival during lipopolysaccharide-induced parturition in late gestation.

Prolonged labor can lead to infection, fetal distress, asphyxia, and life-threatening harm to both the mother and the baby. Surfactant protein A (SP-A) was shown to contribute to the maintenance of pregnancy and timing of term labor. SP-A modulates the stoichiometric expression of the SP-R210L and SP-R210S isoforms of the SP-R210 receptor on alveolar macrophages (AMs). Lack of SP-R210L dysregulates macrophage inflammatory responses. We asked whether SP-A alters normal and inflammation-induced parturition through SP-R210 using SP-A- and SP-R210L-deficient mice. Labor and delivery of time-pregnant mice were monitored in real time using a time-lapse infrared camera. Intrauterine injection with either vehicle or Escherichia coli lipopolysaccharide (LPS) on embryonic (E) day 18.5 post coitus was used to assess the effect of gene disruption in chorioamnionitis-induced labor. We report that either lack of SP-A or disruption of SP-R210L delays parturition by 0.40 and 0.55 days compared with controls, respectively. LPS induced labor at 0.60, 1.01, 0.40, 1.00, and 1.31 days earlier than PBS controls in wild type (WT), SP-A-deficient, littermate controls, heterozygous, and homozygous SP-R210L-deficient mice, respectively. Lack of SP-A reduced litter size in PBS-treated mice, whereas the total number of pups delivered was similar in all LPS-treated mice. The number of live pups, however, was significantly reduced by 50%-70% in SP-A and SP-R210L-deficient mice compared with controls. Differences in gestational length were not associated with intrauterine growth restriction. The present findings support the novel concept that the SP-A/SP-R210 pathway modulates timely labor and delivery and supports fetal lung barrier integrity during fetal-to-neonatal transition in term pregnancy.NEW & NOTEWORTHY To our knowledge, this study is the first to report that SP-A prevents delay of labor and inflammation-induced stillbirth through the receptor SP-R210L.

Overfeeding in the early postnatal period aggravates inflammation and hepatic insulin sensitivity in the 5α-dihydrotestosterone-induced animal model of PCOS.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and is closely associated with chronic low-grade inflammation and insulin resistance. To clarify the contribution of prepubertal weight gain to the development of insulin resistance in PCOS, we investigated the effects of early postnatal overfeeding on inflammatory and energy-sensing pathways as well as on markers of insulin signaling in the liver of the PCOS rat model. Obesity induced by overfeeding was achieved by reducing litter size, while the PCOS-like condition was developed by treatment with 5α-dihydrotestosterone (DHT). Western blot and qPCR were used to analyze the expression of pro-inflammatory transcription factors and cytokines, as well as markers of the energy sensing and insulin signaling pathways. The results showed that hepatic insulin sensitivity was impaired only in DHT-treated rats raised in small litters, as evidenced by increased phosphorylation of IRS1 on Ser307 and decreased expression of total IRS1. Postnatal overfeeding stimulated JNK1 activation independent of hyperandrogenemia; nevertheless, the synergistic effect of both factors triggered NLRP3 activation and increased IL1β expression in the small litter DHT-treated group. This pro-inflammatory state was accompanied by decreased activatory phosphorylation of AMPK and reduced levels of its protein targets. Overfeeding in the early postnatal period leads to a decrease in hepatic insulin sensitivity in the rat model of PCOS, which is associated with decreased activation of AMPK and stimulation of the hepatic NLRP3-IL1β signaling pathway. Accordingly, the inhibition of NLRP3 activation could provide a basis for the development of new therapeutic strategies for the treatment of insulin resistance in women with PCOS.

Fish oil supplementation in obese rats ameliorates metabolic syndrome response.

Accumulation of visceral adipose tissue is associated with metabolic syndrome (MS), insulin resistance, and dyslipidemia. Here we examined several morphometric and biochemical parameters linked to MS in a rodent litter size reduction model, and how a 30-day fish oil (FO) supplementation affected these parameters. On day 3 post-birth, pups were divided into groups of ten or three. On day 22, rats were split into control (C) and small litter (SL) until 60 days old. Then, after metabolic disturbance and obesity were confirmed, FO supplementation started for 30 days and the new groups were named control (C), FO supplemented (FO), obese (Ob), and obese FO supplemented (ObFO). Comparison was performed by Student t-test or 2-way ANOVA followed by Tukey post hoc test. At the end of the 60-day period, SL rats were hyperphagic, obese, hypoinsulinemic, normoglycemic, and had high visceral fat depot and high interleukin (IL)-6 plasma concentration. Obese rats at 90 days of age were fatter, hyperphagic, hyperglycemic, hypertriacylgliceromic, hipoinsulinemic, with low innate immune response. IL-6 production ex vivo was higher, but in plasma it was not different from the control group. FO supplementation brought all biochemical changes to normal values, normalized food intake, and reduced body weight and fat mass in obese rats. The innate immune response was improved but still not as efficient as in lean animals. Our results suggested that as soon MS appears, FO supplementation must be used to ameliorate the morpho- and biochemical effects caused by MS and improve the innate immune response.

Litter reduction-induced obesity promotes early depressive-like behavior and elevated prefrontal cortex GFAP expression in male offspring

AimsThe present study was developed to investigate how litter reduction-induced obesity promotes early depressive-related behaviors in rodent offspring. Main methodsWe employed a standardized litter size reduction protocol, dividing litters into groups: normal litters (NL), consisting of six males and six females pups and small litters (SL), comprising two males and two females pups. Maternal behavior was monitored during the initial week of lactation. Subsequently, we assessed the pups for weight gain, locomotor activity, social play behavior, and performance in forced swimming test. We further evaluated the weights of retroperitoneal and perigonadal fat tissues, along with the expression of glial fibrillary acidic pprotein (GFAP) in the hippocampus and prefrontal cortex of the offspring. Key findingsOur results indicated that litter size reduction led to an increased the maternal behavior. In contrast, offspring from the SL group displayed greater weight gain and increased, retroperitoneal and perigonadal fat. Both male and female rodents in the SL group exhibited decreased social play behavior, and male offspring spent more time immobile during the forced swimming test, suggesting a depressive-like phenotype. Notably, we observed an increase in the GFAP expression in the prefrontal cortex of male rodents, with a trend toward increased expression in the hippocampus. SignificanceObesity may facilitate the development of early depressive-like behaviors, potentially associated with elevated GFAP expression in the prefrontal cortex.

Characterizing Pregnancy Outcomes in a Humanized Mouse Model of Sickle Cell Disease

Background: Sickle cell disease (SCD) is a group of hereditary disorders commonly associated with the distortion of red blood cells (RBC) at low oxygen levels. It is characterized by complications such as vaso-occlusion, anemia, and hemolysis. These complications are lifelong and become extremely relevant during periods of increased physiological stress such as pregnancy. Pregnancy in sickle cell disease (SCD) is associated with an increased risk of complications including, pre-term delivery, deep vein thrombosis, intra-uterine growth restriction, pre-eclampsia, and intra-uterine death. Recent meta-analyses have shown that women with SCD are at 26x greater risk for maternal mortality than their healthy counterparts; a figure which, despite the adoption of improved care plans, has shown little to no significant improvement over the last two decades. While impaired vascular maintenance underlies multiple complications of pregnancy outside of sickle cell disease, it is especially relevant to, and characteristic of sickle cell-related pathologies at baseline and is highly likely to be exacerbated as pregnancy proceeds. Through this study we aimed to characterize the effects of SCD-related vasculopathy on pregnancy outcomes and overall placental health using the Townes humanized mouse model of SCD. Methods: SS (sickle hemoglobin) and AA (normal hemoglobin) mice underwent timed breeding to produce pregnant dams. These dams were housed under normal conditions until 17.5 days post conception (dpc), at which point they began undergoing procedures for analysis including 24-hour urine collection, high-resolution ultrasound analysis (18.5dpc), and post-mortem analysis of pregnancy outcomes and tissue collection (18.5dpc). Included in this report are gross pregnancy outcomes, histological assessments of placental tissue, and reports from ultrasound analysis including 3-D volume measures, placental vascularization renders, and laser-Doppler assessment of uterine and umbilical arteries. Continuing research efforts will further utilize tissues from this study to evaluate the biochemical interactions influencing poor pregnancy outcomes related to SCD. Results: These studies show that the SCD mice recapitulate many similarly poor outcomes as women. We observed: reduced litter sizes (AA 6.9 ± 1.5 embryos vs SS 5.2 ± 1.2 embryos**), fetal weight (AA 0.49 ± 0.14g vs SS 0.38 ± 0.16g*), viability of embryos (AA 100.0% IQR 0.0 vs SS 20.0% IQR 33.3****), and maternal mortality (AA 0.0% vs SS 8.7%, OR = 4.3 ns). In assessing placental histology, we identified evidence of vasculopathy common to end organ damage in SCD such as increased presence of avascular areas, reduced relative labyrinth area (AA 55.6 ± 8.6% vs SS 44.7 ± 6.0%*) and reduced vascular density (AA 38.9 ± 6.2% vs SS 34.4 ± 7.0%*) which are likely responsible for worsening outcomes. Additional pathologies include increased occurrence of placental ectasia, calcification of the labyrinth, vascular thrombi, and perivascular fibrosis when compared to controls. Further, ultrasound analysis revealed several measures of placental insufficiency amongst SS mice that were significantly impaired including uterine blood flow and an overall reduction in placental vascularization and oxygenation. Conclusions: SCD mice demonstrate many similar pregnancy outcomes as humans, allowing for increased translational application. We've shown these outcomes to be severe and largely driven by vascular impairment specifically within the placenta, the main maternal-fetal interface. This study serves as the groundwork for future studies aimed at investigating the underlying mechanisms of these outcomes while also establishing baseline measures and novel methods of approach towards the broader goal of improving obstetric disparities faced by women with SCD.

Common Infectious and Parasitic Diseases in Goats of Tropical Africa and their Impacts on Production Performance: A Review

Available scientific studies on goat diseases in tropical Africa are limited to specific regions or specific diseases. This study aimed to review scientific research findings on goat diseases in tropical Africa, focusing on their prevalence and impacts on production performance. All main diseases, such as parasitic, viral, and bacterial diseases, are included in the present study. Studies conducted in different countries have revealed high prevalence rates of gastrointestinal parasites exceeding 95%. These parasites resulted in growth retardation and reduced carcass weight at slaughter. Management of mites could decrease production and reproductive function. Trypanosomiasis led to decreased hematocrit levels, abortions, low birth weight, and high kid mortality. The prevalence of trypanosomiasis has been different across regions, ranging from 2.95% to 57.1%. Peste des Petits Ruminants has been reported in many African countries, causing significant outbreaks with seroprevalence rates ranging from 30% to 55%. Rift Valley fever was characterized by high mortality in adult goats (20-30%) and numerous abortions 2 weeks after infection, with seroprevalence rates ranging up to 25.8%. Contagious Caprine Pleuropneumonia indicated high morbidity (approximately 100%) and high mortality (80% to 100%), with prevalence ranging from 22% to 39% in abattoirs and from 35% to 52% in farms. Brucellosis did not affect the weight of infected animals but reduced litter size in goats and disrupts vital organs. This review highlights the extent of goat diseases in tropical Africa to determine the most appropriate prevention and control strategies.

Observations about declining fertility in a feline breeding colony

Feline breeding colonies are important to the feline industry by preserving traits desirable for a particular breed or in research settings by maintaining medically valuable genetic traits. As breeding females age, their reproductive efficiency declines. The objective of this study was to determine the most common causes of infertility in breeding females that were producing fewer kittens. Knowing the cause and average age of infertility would allow management decisions to be made for the betterment of the colony. The medical records of 70 queens retired from breeding from a single research colony were examined for litter size and number, fertility over their lifespan, and age and reason for removal from breeding stock. Sections of uterus and ovaries were evaluated using gross and histopathological examination for a subset of these queens (46). The data suggests that mature, continuously breeding female cats may show signs of reduced fertility (infertile matings or reduced litter size) as early as 3 years of age and may be a result of undiagnosed Cystic Endometrial Hyperplasia (CEH), endometritis, pyometra and/or ovarian cysts. Evaluation of breeding queens should include periodic ultrasounds to monitor for ovarian cysts and evidence of CEH. Retiring animals from breeding once signs of infertility become apparent is recommended.