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1.
Front Endocrinol (Lausanne) ; 13: 839034, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35518932

RESUMO

Background: Obesity is associated with a decrease in testicular function, yet the effects and mechanisms relative to different stages of sexual development remain unclear. The aim of this study is to determine whether high-fat diet-induced obesity impairs male fertility during puberty and in adulthood, and to ascertain its underlying mechanisms. This study aims to further reveal whether restoring to a normal diet can improve impaired fertility. Methods: Male mice were divided into 6 groups: the group N and H exposed to a normal diet or high-fat diet during puberty. The group NN or NH were further maintained a normal diet or exposed to high-fat diet in adulthood, the group HH or HN were further maintained high-fat diet or switched to normal diet in adulthood. Metabolic parameters, fertility parameters, testicular function parameters, TUNEL staining and testicular function-related proteins were evaluated, respectively. Results: The fertility of the mice in the high-fat diet group was impaired, which validated by declines in pregnancy rates and litter weight loss. Further analysis demonstrated the increased level of oxidative stress, the increased number of spermatogenic cell apoptosis and decreased number of sperm and decreased acrosome integrity. The expression of steroidogenic acute regulatory (StAR) and spermatogenesis related proteins (WT-1) decreased. Fertility among the HN group recovered, accompanied by the recovery of metabolism, fertility and testicular function parameters, StAR and WT-1 expression. Conclusions: The findings suggest that high-fat diet-induced obesity impairs male fertility during puberty and in adulthood. The loss of acrosome integrity, the increase of oxidative stress, the increase of cells apoptosis and the down-regulation of StAR and WT-1 may be the underlying mechanisms. Switching from high-fat diets during puberty to normal diets in adulthood can improve male fertility.


Assuntos
Dieta Hiperlipídica , Maturidade Sexual , Animais , Dieta Hiperlipídica/efeitos adversos , Feminino , Fertilidade , Masculino , Camundongos , Camundongos Obesos , Obesidade/complicações , Gravidez
2.
Proc Biol Sci ; 289(1974): 20220670, 2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35506232

RESUMO

Epigenetic inheritance can result in plastic responses to changing environments being faithfully transmitted to offspring. However, it remains unclear how epigenetic mechanisms such as DNA methylation can contribute to multigenerational acclimation and adaptation to environmental stressors. Brook charr (Salvelinus fontinalis), an economically important salmonid, is highly sensitive to thermal stress and is of conservation concern in the context of climate change. We studied the effects of temperature during parental sexual maturation and offspring rearing on whole-genome DNA methylation in brook charr juveniles (fry). Parents were split between warm and cold temperatures during sexual maturation, mated in controlled breeding designs, then offspring from each family were split between warm (8°C) and cold (5°C) rearing environments. Using whole-genome bisulfite sequencing, we found 188 differentially methylated regions (DMRs) due to parental maturation temperature after controlling for family structure. By contrast, offspring rearing temperature had a negligible effect on offspring methylation. Stable intergenerational inheritance of DNA methylation and minimal plasticity in progeny could result in the transmission of acclimatory epigenetic states to offspring, priming them for a warming environment. Our findings have implications pertaining to the role of intergenerational epigenetic inheritance in response to ongoing climate change.


Assuntos
Metilação de DNA , Truta , Aclimatação , Animais , Epigênese Genética , Maturidade Sexual , Truta/genética
3.
J Anim Sci ; 100(4)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35363309

RESUMO

Energy demands during lactation greatly influence sow body condition and piglet performance. We hypothesized that primiparous sows or sows with reduced body condition would produce piglets with reduced growth and delayed sexual maturation. Eight weekly farrowing seasons were used to evaluate sow body condition (post-farrowing, PF and weaning, WN) and piglet growth from 157 dams. Body condition was measured at PF and WN using sow calipers (last rib and hip) and 10th rib ultrasound. Sows were categorized as thin, moderate, or fat by caliper (PF or WN). Individual pig weights were recorded on approximately 1, 10, WN, 45, 100, and 145 d of age. At 100 and 145 d of age, 10th-rib backfat and loin eye area were measured on 567 pigs and first estrus was monitored in 176 gilts reserved for breeding selection beginning at approximately 170 d of age. Sows had similar (P > 0.10) PF last rib caliper measurements but at WN, first parity sows had the smallest caliper measurements compared to other parities (P < 0.05). Parities 1, 2, and 3 sows had similar (P > 0.10) loin eye area at PF; however, at WN first parity sows had the smallest loin eye area (P < 0.05; 38.2 ± 0.63 cm2). Parity 1 sows had the greatest (P < 0.05) reduction of backfat and loin eye area over the lactation period (-2.9 ± 0.31 mm and -2.6 ± 0.49 cm2, respectively). At 1 d of age and WN, piglets from first parity sows weighed the least (P < 0.05) but were the heaviest (P < 0.05) at 100 and 145 d of age. Pigs from first parity litters had larger (P < 0.05) loin eye area at 100 and 145 d of age and greater backfat (P < 0.05) at 145 d of age. Fat sows at WN (last rib or hip) had the lightest (P < 0.05) piglets at 10 d of age and WN. However, at 45 d of age, piglets from fat sows (last rib or hip) were heavier (P < 0.05) than piglets from moderate and thin sows. Tenth rib backfat at 100 and 145 d of age tended (P < 0.10) to be less in pigs reared by thin sows (PF and WN hip). Tenth rib loin eye area was similar among pigs reared by fat, moderate, or thin sows. Gilts developed in litters from fourth parity sows had (P < 0.05) delayed age at puberty in contrast to gilts from first or third parity sows (200.9 ± 4.96 d vs. 189.0 ± 2.29 d and 187.5 ± 2.84 d, respectively). Although progeny body weights were typically less from first parity dams through 45 d of age, these progeny were similar or heavier at 100 and 145 d of age in contrast to progeny from other parities. Furthermore, gilt progeny from first parity dams did not have delayed pubertal attainment.


Young female swine have a greater challenge successfully producing and raising a litter of piglets as they are still maturing themselves and nursing is an extremely energy demanding event. Piglet growth during the nursing phase can have extended impact on growth and development later in life. Piglets raised by young first-time mothers were smaller at birth and weaning but grew to similar weight and body composition later in life as their contemporaries raised by older more mature mothers. Young female pigs raised by first-time mothers had similar or better sexual maturity than counterparts raised by mature mothers. These findings indicate that piglets reared by first time mothering dams will not have detrimental effects on maturity and reproductive parameters. Producers can confidently select females that were reared by first-time mothers for the breeding herd without sacrificing quality.


Assuntos
Lactação , Maturidade Sexual , Animais , Feminino , Paridade , Gravidez , Sus scrofa , Suínos , Desmame
4.
Int J Mol Sci ; 23(7)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35409243

RESUMO

The mammary gland is a compound, branched tubuloalveolar structure and a major characteristic of mammals. The mammary gland has evolved from epidermal apocrine glands, the skin glands as an accessory reproductive organ to support postnatal survival of offspring by producing milk as a source of nutrition. The mammary gland development begins during embryogenesis as a rudimentary structure that grows into an elementary branched ductal tree and is embedded in one end of a larger mammary fat pad at birth. At the onset of ovarian function at puberty, the rudimentary ductal system undergoes dramatic morphogenetic change with ductal elongation and branching. During pregnancy, the alveolar differentiation and tertiary branching are completed, and during lactation, the mature milk-producing glands eventually develop. The early stages of mammary development are hormonal independent, whereas during puberty and pregnancy, mammary gland development is hormonal dependent. We highlight the current understanding of molecular regulators involved during different stages of mammary gland development.


Assuntos
Glândulas Mamárias Animais , Maturidade Sexual , Animais , Feminino , Lactação , Mamíferos , Morfogênese , Gravidez , Transdução de Sinais
5.
Cells ; 11(7)2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35406710

RESUMO

Kisspeptin (KP) and kisspeptin receptor (KPR) are essential for the onset of puberty, development of gonads, and maintenance of gonadal function in both males and females. Hypothalamic KPs and KPR display a high degree of sexual dimorphism in expression and function. KPs act on KPR in gonadotropin releasing hormone (GnRH) neurons and induce distinct patterns of GnRH secretion in males and females. GnRH acts on the anterior pituitary to secrete gonadotropins, which are required for steroidogenesis and gametogenesis in testes and ovaries. Gonadal steroid hormones in turn regulate the KP neurons. Gonadal hormones inhibit the KP neurons within the arcuate nucleus and generate pulsatile GnRH mediated gonadotropin (GPN) secretion in both sexes. However, the numbers of KP neurons in the anteroventral periventricular nucleus and preoptic area are greater in females, which release a large amount of KPs in response to a high estrogen level and induce the preovulatory GPN surge. In addition to the hypothalamus, KPs and KPR are also expressed in various extrahypothalamic tissues including the liver, pancreas, fat, and gonads. There is a remarkable difference in circulating KP levels between males and females. An increased level of KPs in females can be linked to increased numbers of KP neurons in female hypothalamus and more KP production in the ovaries and adipose tissues. Although the sexually dimorphic features are well characterized for hypothalamic KPs, very little is known about the extrahypothalamic KPs. This review article summarizes current knowledge regarding the sexual dimorphism in hypothalamic as well as extrahypothalamic KP and KPR system in primates and rodents.


Assuntos
Kisspeptinas , Caracteres Sexuais , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Feminino , Hormônio Liberador de Gonadotropina , Kisspeptinas/metabolismo , Masculino , Maturidade Sexual
6.
PLoS One ; 17(4): e0267211, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35486595

RESUMO

Mammary gland is present in all mammals and usually functions in producing milk to feed the young offspring. Mammogenesis refers to the growth and development of mammary gland, which begins at puberty and ends after lactation. Pregnancy is regulated by various cytokines, which further contributes to mammary gland development. Epithelial cells, including basal and luminal cells, are one of the major components of mammary gland cells. The development of basal and luminal cells has been observed to significantly differ at different stages. However, the underlying mechanisms for differences between basal and luminal cells have not been fully studied. To explore the mechanisms underlying the differentiation of mammary progenitors or their offspring into luminal and myoepithelial cells, the single-cell sequencing data on mammary epithelia cells of virgin and pregnant mouse was deeply investigated in this work. We evaluated features by using Monte Carlo feature selection and plotted the incremental feature selection curve with support vector machine or RIPPER to find the optimal gene features and rules that can divide epithelial cells into four clusters with different cell subtypes like basal and luminal cells and different phases like pregnancy and virginity. As representations, the feature genes Cldn7, Gjb6, Sparc, Cldn3, Cited1, Krt17, Spp1, Cldn4, Gjb2 and Cldn19 might play an important role in classifying the epithelial mammary cells. Notably, seven most important rules based on the combination of cell-specific and tissue-specific expressions of feature genes effectively classify the epithelial mammary cells in a quantitative and interpretable manner.


Assuntos
Glândulas Mamárias Animais , Maturidade Sexual , Animais , Diferenciação Celular/genética , Células Epiteliais/metabolismo , Feminino , Lactação/genética , Mamíferos , Glândulas Mamárias Animais/metabolismo , Camundongos , Gravidez
7.
Ecotoxicol Environ Saf ; 236: 113515, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35427877

RESUMO

Tetramethyl bisphenol A (TMBPA) is a commonly used bisphenol analog, used as a fire retardant. However, whether it inhibits the function of Leydig cells in late puberty remains unclear. In this study, 35-day-old male Sprague-Dawley rats were gavaged with 0, 10, 100, and 200 mg/kg body weight TMBPA for 21 days. TMBPA significantly reduced serum testosterone levels at 10 mg/kg and higher doses without altering serum luteinizing hormone and follicle-stimulating hormone levels. TMBPA significantly increased serum iron concentraion while reducing the ratio of serum glutathione (GSH) and GSH/GSSG (oxidized glutathione disulfide). In addition, TMBPA significantly increased testicular iron amount at 10 mg/kg and higher doses and malondialdehyde level at 200 mg/kg. TMBPA down-regulated the expression of Leydig cell genes, including Nr5a1, Star, Scarb1, Insl3, Cyp11a1, Cyp17a1, Hsd17b3, and Hsd11b1, and their proteins. In addition, TMBPA markedly down-regulated the expression of genes in the ferroptosis pathway (Tp53, Slc7a11, Sod1, Sod2, Cat, Sqstm1, Keap1, and Hmox1). TMBPA significantly reduced the levels of ferroptosis pathway proteins (TP53, SLC7A11, GPX4, SQSTM1, KEAP1, NRF2, and HMOX1) in Leydig cells in vivo. Immature and adult Leydig cell culture in vitro also showed that TMBPA significantly reduced testosterone concentrations in the medium, which can be reversed by a ferroptosis inhibitor. After 24 h of culture in primary Leydig cells at 10 and 50 µM, TMBPA significantly induced reactive oxygen species and lowered the mitochondrial membrane potential. TMBPA also altered protein levels in the ferroptosis pathway in Leydig cells in vitro. In conclusion, TMBPA directly inhibits the activity of rat Leydig cell steroidogenic enzymes and induces the ferroptosis of Leydig cells, thereby inhibiting the testosterone synthesis of Leydig cells in the late puberty.


Assuntos
Ferroptose , Células Intersticiais do Testículo , Animais , Compostos Benzidrílicos , Di-Hidrotaquisterol/metabolismo , Ferro/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Células Intersticiais do Testículo/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Fenóis , Ratos , Ratos Sprague-Dawley , Proteína Sequestossoma-1/metabolismo , Maturidade Sexual , Testosterona
8.
Front Endocrinol (Lausanne) ; 13: 826920, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370944

RESUMO

Precocious male maturation causes reduced welfare and increased production costs in Atlantic salmon (Salmo salar) aquaculture. The pituitary produces and releases follicle-stimulating hormone (Fsh), the gonadotropin triggering puberty in male salmonids. However, little is known about how Fsh production is regulated in Atlantic salmon. We examined, in vivo and ex vivo, transcriptional changes of gonadotropin-related genes accompanying the initial steps of testis maturation, in pituitaries of males exposed to photoperiod and temperature conditions promoting maturation (constant light and 16°C). Pituitary fshb, lhb and gnrhr2bba transcripts increased in vivo in maturing males (gonado-somatic index > 0.1%). RNA sequencing (RNAseq) analysis using pituitaries from genetically similar males carrying the same genetic predisposition to mature, but differing by responding or not responding to stimulatory environmental conditions, revealed 144 differentially expressed genes, ~2/3rds being up-regulated in responders, including fshb and other pituitary hormones, steroid-related and other puberty-associated transcripts. Functional enrichment analyses confirmed gene involvement in hormone/steroid production and gonad development. In ex vivo studies, whole pituitaries were exposed to a selection of hormones and growth factors. Gonadotropin-releasing hormone (Gnrh), 17ß-estradiol (E2) and 11-ketotestosterone (11-KT) up-regulated gnrhr2bba and lhb, while fshb was up-regulated by Gnrh but down-regulated by 11-KT in pituitaries from immature males. Also pituitaries from maturing males responded to Gnrh and sex steroids by increased gnrhr2bba and lhb transcript levels, but fshb expression remained unchanged. Growth factors (inhibin A, activin A and insulin-like growth factor 1) did not change gnrhr2bba, lhb or fshb transcript levels in pituitaries either from immature or maturing males. Additional pituitary ex vivo studies on candidates identified by RNAseq showed that these transcripts were preferentially regulated by Gnrh and sex steroids, but not by growth factors, and that Gnrh/sex steroids were less effective when incubating pituitaries from maturing males. Our results suggest that a yet to be characterized mechanism up-regulating fshb expression in the salmon pituitary is activated in response to stimulatory environmental conditions prior to morphological signs of testis maturation, and that the transcriptional program associated with this mechanism becomes unresponsive or less responsive to most stimulators ex vivo once males had entered pubertal developmental in vivo.


Assuntos
Salmo salar , Animais , Expressão Gênica , Gonadotropinas/metabolismo , Gonadotropinas/farmacologia , Gonadotropinas Hipofisárias/genética , Masculino , Salmo salar/genética , Salmo salar/metabolismo , Maturidade Sexual/genética
9.
Elife ; 112022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35258453

RESUMO

Reproductive synchrony generally occurs in various group-living animals. However, the underlying mechanisms remain largely unexplored. The migratory locust, Locusta migratoria, a worldwide agricultural pest species, displays synchronous maturation and oviposition when forms huge swarm. The reproductive synchrony among group members is critical for the maintenance of locust swarms and population density of next generation. Here, we showed that gregarious female locusts displayed more synchronous sexual maturation and oviposition than solitarious females and olfactory deficiency mutants. Only the presence of gregarious male adults can stimulate sexual maturation synchrony of female adults. Of the volatiles emitted abundantly by gregarious male adults, the aggregation pheromone, 4-vinylanisole, was identified to play key role in inducing female sexual maturation synchrony. This maturation-accelerating effect of 4-vinylanisole disappeared in the females of Or35-/- lines, the mutants of 4-vinylanisole receptor. Interestingly, 4-vinylanisole displayed a time window action by which mainly accelerates oocyte maturation of young females aged at middle developmental stages (3-4 days post adult eclosion). We further revealed that juvenile hormone/vitellogenin pathway mediated female sexual maturation triggered by 4-vinylanisole. Our results highlight a 'catch-up' strategy by which gregarious females synchronize their oocyte maturation and oviposition by time-dependent endocrinal response to 4-vinylanisole, and provide insight into reproductive synchrony induced by olfactory signal released by heterosexual conspecifics in a given group.


Since 2019, a plague of flying insects known as migratory locusts has been causing extensive damage to crops in East Africa. Migratory locusts sometimes live a solitary lifestyle but, if environmental conditions allow, they form large groups containing millions of individuals known as swarms that are responsible for causing locust plagues.Locusts are able to maintain such large swarms because they can aggregate and synchronize. When they live in swarms, individual locusts produce odors that are sensed by other individuals in the group. For example, an aggregation pheromone, called 4-vinylanisole, is known to help keep large groups of locusts together. However, it is less clear how odors synchronize the reproductive cycles of the females in a swarm so that they are ready to mate with males and lay their eggs at the same time. To address this question, Chen et al. examined when female locusts reached sexual maturity after they were exposed to odors produced by other locusts living alone or in groups. The experiments found that only 4-vinylanisole, which was abundantly released by adult male locusts living in groups, stimulated female locusts to reach sexual maturity at the same time. This odor increased the levels of a hormone known as juvenile hormone in less-developed females to help them reach sexual maturity sooner. These findings demonstrate that when migratory locusts are living in swarms, male locusts promote the female locusts to reach sexual maturity at the same time by promoting less-developed females to 'catch up' with other females in the group. A next step will be to investigate the neural and molecular mechanisms underlying the 'catch up' effect induced by 4-vinylanisole.


Assuntos
Gafanhotos , Locusta migratoria , Animais , Feminino , Locusta migratoria/fisiologia , Masculino , Feromônios/metabolismo , Maturidade Sexual , Estirenos/metabolismo
10.
Trop Anim Health Prod ; 54(2): 138, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35312838

RESUMO

The present study aimed to compare the growth rate, feeding behavior, reproductive development, and concentrations of GH and leptin in Sahiwal heifers exposed to direct bull contact, bull contact through a fenceline, or isolated from bulls. Overall, 24 heifers were allotted to three treatment groups (n = eight/group) based on birth weight, body weight, and age. Heifers from the non-exposed group (NBE) remained isolated from bulls; heifers stimulated by fenceline bull contact (FBE) remained continuously exposed to bulls through a fenceline, and heifers with direct bull contact (DBE+FBE) had direct contact with a bull during 6 h/day plus continuous fenceline bull exposure for the entire 24 h period. It was considered that heifers attained puberty when progesterone concentration was >1 ng/mL. Biostimulated heifers achieved puberty at both a lower age and body weight (P < 0.05) than NBE heifers. Overall, average daily gain (g/day) was greater in DBE+FBE (516.3 ± 4.5) and FBE (501.6 ± 4.3) than in NBE (441.8 ± 2.9, respectively; P < 0.01). Leptin and growth hormone concentrations were significantly greater in FBE and DBE+FBE than NBE heifers. Both groups of biostimulated heifers devoted more time eating than NBE heifers, P < 0.05). In conclusion, biostimulation of Sahiwal heifers, either by exposing them to bulls through a fenceline or by both fenceline exposure and direct contact, reduced the age of puberty and increased growth performance. Overall, fenceline bull exposure can be recommended as an easy handling management to stimulate reproductive precocity and growth rate in heifers.


Assuntos
Reprodução , Maturidade Sexual , Animais , Bovinos , Feminino , Masculino , Progesterona/farmacologia
11.
Cells ; 11(5)2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-35269513

RESUMO

Retinoic acid signaling is indispensable for the completion of spermatogenesis. It is known that loss of retinoic acid nuclear receptor alpha (RARA) induces male sterility due to seminiferous epithelium degeneration. Initial genetic studies established that RARA acts in Sertoli cells, but a recent paper proposed that RARA is also instrumental in germ cells. In the present study, we have re-assessed the function of RARA in germ cells by genetically ablating the Rara gene in spermatogonia and their progenies using a cell-specific conditional mutagenesis approach. We show that loss of Rara in postnatal male germ cells does not alter the histology of the seminiferous epithelium. Furthermore, RARA-deficient germ cells differentiate normally and give rise to normal, living pups. This establishes that RARA plays no crucial role in germ cells. We also tested whether RARA is required in Sertoli cells during the fetal period or after birth. For this purpose, we deleted the Rara gene in Sertoli cells at postnatal day 15 (PN15), i.e., after the onset of the first spermatogenic wave. To do so, we used temporally controlled cell-specific mutagenesis. By comparing the testis phenotypes generated when Rara is lost either at PN15 or at embryonic day 13, we show that RARA exerts all of its functions in Sertoli cells not at the fetal stage but from puberty.


Assuntos
Células de Sertoli , Maturidade Sexual , Animais , Masculino , Receptor alfa de Ácido Retinoico/genética , Espermatogônias , Tretinoína
12.
Curr Biol ; 32(8): 1822-1828.e4, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35245461

RESUMO

Adequate nutrition is essential for normal reproductive function, which is vital for species to survive. In humans and other mammals, starvation and undernutrition deplete fat reserves and cause weight loss, attenuating the function of the reproductive axis and causing hypogonadism.1-4 Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) spend 7 months of every year in hibernation without food and water. Hibernating squirrels alternate between periods of torpor and interbout arousal (IBA), when animals temporarily return to an active-like state.5 The physiological significance of IBA is unclear, but it is thought to be essential for hibernation in animals that drop their body temperature to 2°C-4°C during torpor. Here, we report that juvenile male ground squirrels initiate reproductive maturation during their first hibernation season, despite prolonged undernutrition and profound weight loss. We show that the hypothalamic reproductive axis undergoes activation during interbout arousals in the middle of hibernation, triggering production of luteinizing hormone and testosterone, and promoting testicular growth. Initiation of sexual maturation is circannually entrained and is independent of physiological state, ambient temperature, and food availability. Our study suggests a role for interbout arousals during hibernation and uncovers the neurophysiological mechanism of reproductive axis activation during conditions of extreme negative energy balance. VIDEO ABSTRACT.


Assuntos
Hibernação , Desnutrição , Animais , Hibernação/fisiologia , Masculino , Sciuridae/fisiologia , Maturidade Sexual , Perda de Peso
13.
Histochem Cell Biol ; 157(3): 347-357, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35239019

RESUMO

The cystine-glutamate transporter (xCT) is responsible for the transport of cystine into cells. We recently found that xCT-deficient (xCTKO) aged mice maintained a higher rate of ovulation and ovarian weight compared with wild-type (WT) mice. It has been reported that a xCT deficiency in cultured cells induces autophagy through the suppression of mTOR survival pathways. We have previously reported that starvation in neonatal mice increases the number of primordial follicles with concomitant autophagy activation. Therefore, we investigated age-related changes in follicle reserve and fertility in xCTKO mice and clarified whether the PI3K/AKT/mTOR signaling pathway contributes to this. The numbers of offspring in the xCTKO mice aged 10 and 12 months were significantly higher than those in the WT mice. The primordial follicle numbers in xCTKO neonatal mice tended to be higher than WT mice during all times evaluated. In contrast, the primary follicle number was significantly lower in the xCTKO mice at 60 h after birth. The expression of p-AKT, which promotes follicle development, was significantly lower in xCTKO mice than that in WT mice, whereas the expression ratios of LC3-II/LC3-I were significantly higher. The xCTKO mice had significantly more primordial follicles than WT mice at 2 months of age and showed a similar trend at 13-15 months of age. These results suggest that the maintenance of fertility in aged xCTKO mice can be attributed to high follicle reserve after puberty by suppression of follicle activation during the neonatal period.


Assuntos
Cistina , Fosfatidilinositol 3-Quinases , Sistema X-AG de Transporte de Aminoácidos/metabolismo , Animais , Cistina/metabolismo , Feminino , Fertilidade/genética , Camundongos , Folículo Ovariano/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Maturidade Sexual
14.
Trop Anim Health Prod ; 54(2): 111, 2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35201438

RESUMO

This study investigated phenotypic differences of zebu females from four breeds using variables of growth, feed efficiency, and age at first calving. Weights throughout the life were recorded, and a growth curve was fitted using the Gompertz model. The growth was also evaluated at standardized ages (205, 365, and 550 days) using the body weight and the total and daily weight gains. The Kleiber index and age at first calving were used as measures of feed efficiency and sexual precocity, respectively, totaling 25 variables. New variables were created using the factor analysis and used in new multivariate analyzes. Only six factors explained 95.41% of the total variance and were used for the subsequent analyses. The factors were defined as maturity, precocity, feed efficiency postweaning, feed efficiency post 1 year of age, puberty, and birth weight. There were differences between breeds according to the multivariate analysis of variance. Each breed appeared in a quadrant on the Biplot graph, showing relationship with different factors, demonstrating the diversity of zebu females. There is a difference in growth, feed efficiency, and sexual precocity in Brazilian zebu females, allowing the identification of potentials of the animals and help breeders and decision-makers.


Assuntos
Maturidade Sexual , Ganho de Peso , Animais , Brasil , Bovinos , Feminino
15.
Best Pract Res Clin Endocrinol Metab ; 36(1): 101618, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35183440

RESUMO

Puberty marks the end of childhood and is a period when individuals undergo physiological and psychological changes to achieve sexual maturation and fertility. The onset of puberty is first detected as an increase in pulsatile secretion of gonadotropin-releasing hormone (GnRH). Pubertal onset is regulated by genetic, nutritional, environmental, and socio-economic factors. Disturbances affecting pubertal timing result in adverse health conditions later in life. Human genetic studies show that around 50-80% of the variation in pubertal onset is genetically determined. The genetic control of pubertal timing has been a field of active investigation in attempt to better understand the neuroendocrine control of this relevant period of life. Large populational studies and patient cohort-based studies have provided insights into the genetic regulation of pubertal onset. In this review, we discuss these discoveries and discuss potential mechanisms for how implicated genes may affect pubertal timing.


Assuntos
Puberdade Tardia , Puberdade , Hormônio Liberador de Gonadotropina/genética , Humanos , Puberdade/genética , Puberdade Tardia/genética , Maturidade Sexual/genética
16.
J Exp Zool A Ecol Integr Physiol ; 337(5): 491-500, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35226410

RESUMO

Age determination provides crucial data regarding the life history of a species. Skeletochronology is considered to be a reliable method for age determination but is seldom applied to the genus Phrynocephalus (Agamidae) as it requires careful bone histological analysis to determine the formation of the lines of arrested growth (LAGs). We analyzed LAGs in different bones of Phrynocephalus vlangalii, a small, high-altitude lizard, and demonstrated that the phalanges are the best materials for skeletochronology in this species. We also found that the proximal half of the phalangeal diaphysis exhibits the most complete LAGs because of the unidirectional longitudinal growth of the phalange. Histologically, as the embryo bone that developed during the embryonic period was preserved even in very old individuals, no LAGs were eroded by endosteal resorption in the phalanges. The maximum age was 4 years for males and 5 years for females. It was determined that the age at maturity was 3 years for males and 2 or 3 years for females. On the basis of age determination, the age structures of both sexes were compared, and age-specific growth differences between the sexes were also analyzed. No differences in the snout-vent length were observed between sexes in any age group. However, the tail length of males aged 3 and above was significantly longer than that of females. Thus, the use of phalanges in the age determination of P. vlangalii is effective and can be widely applied to the ecological studies of this species as well as other small lizards.


Assuntos
Lagartos , Altitude , Animais , Osso e Ossos , Feminino , Lagartos/fisiologia , Longevidade , Masculino , Maturidade Sexual
17.
Cell Mol Life Sci ; 79(3): 136, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35181820

RESUMO

Sertoli cells (Sc) are the sole target of follicle-stimulating hormone (FSH) in the testis and attain functional maturation post-birth to significantly augment germ cell (Gc) division and differentiation at puberty. Despite having an operational microRNA (miRNA) machinery, limited information is available on miRNA-mediated regulation of Sc maturation and male fertility. We have shown before that miR-92a-3p levels decline in pubertal rat Sc. In response to FSH treatment, the expressions of FSH Receptor, Claudin11 and Klf4 were found to be elevated in pubertal rat Sc coinciding with our finding of FSH-induced decline in miR-92a-3p levels. To investigate the association of miR-92a-3p and spermatogenesis, we generated transgenic mice where such pubertal decline of miR-92a-3p was prevented by its overexpression in pubertal Sc under proximal Rhox5 promoter, which is known to be activated specifically at puberty, in Sc. Our in vivo observations provided substantial evidence that FSH-induced decline in miR-92a-3p expression during Sc maturation acts as an essential prerequisite for the pubertal onset of spermatogenesis. Elevated expression of miR-92a-3p in post-pubertal testes results into functionally compromised Sc, leading to impairment of the blood-testis barrier formation and apoptosis of pre-meiotic Gc, ultimately culminating into infertility. Collectively, our data suggest that regulation of miR-92a-3p expression is crucial for Sc-mediated induction of active spermatogenesis at puberty and regulation of male fertility.


Assuntos
Diferenciação Celular , Fertilidade , Hormônio Foliculoestimulante/farmacologia , Células Germinativas/citologia , MicroRNAs/genética , Células de Sertoli/citologia , Testículo/citologia , Animais , Feminino , Células Germinativas/efeitos dos fármacos , Células Germinativas/metabolismo , Hormônios/farmacologia , Masculino , Camundongos , Camundongos Transgênicos , Ratos , Ratos Wistar , Receptores do FSH/genética , Receptores do FSH/metabolismo , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Maturidade Sexual , Espermatogênese , Testículo/efeitos dos fármacos , Testículo/metabolismo
18.
Cells ; 11(3)2022 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-35159359

RESUMO

At the onset of puberty, ovarian follicles become competent to incorporate large amounts of vitellogenin (Vtg). Using an RNAseq-based approach, transcriptomes from pre-vitellogenic (PV) and early vitellogenic (EV) ovaries from wild-caught eel, Anguilla australis, were compared to investigate the expression of specific genes encoding cell junction proteins that could be involved in regulating Vtg uptake. Partial support was found for the mechanical barrier hypothesis proposing that the access of Vtg to the oolemma is restricted by a tight junction (TJ) network within the granulosa cell layer, which changes between the PV and EV stage. Among 25 genes encoding TJ-constituting proteins, five were down-regulated and two were up-regulated. A chemical barrier hypothesis stating that gap junctions (GJs) are involved in modulating Vtg uptake was not supported, as only five GJs were found to be expressed in the ovary with no significant changes in expression between stages. Furthermore, the endocytic pathway was found to be up-regulated during the PV-EV transition. Finally, the study showed that gene expression patterns may help identify suitable candidates involved in the regulation of Vtg uptake, and provided novel sequence data for A. australis, including putative Vtg receptors corresponding to Lr8 and Lrp13 members of the low-density lipoprotein receptor family.


Assuntos
Anguilla , Vitelogeninas , Anguilla/genética , Anguilla/metabolismo , Animais , Feminino , Junções Intercelulares , Ovário/metabolismo , Maturidade Sexual , Vitelogeninas/genética , Vitelogeninas/metabolismo
19.
Hum Reprod Update ; 28(3): 346-375, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35187579

RESUMO

BACKGROUND: According to the Developmental Origins of Health and Disease (DOHaD) hypothesis, environmental changes taking place during early maturational periods may alter normal development and predispose to the occurrence of diverse pathologies later in life. Indeed, adverse conditions during these critical developmental windows of high plasticity have been reported to alter the offspring developmental trajectory, causing permanent functional and structural perturbations that in the long term may enhance disease susceptibility. However, while solid evidence has documented that fluctuations in environmental factors, ranging from nutrient availability to chemicals, in early developmental stages (including the peri-conceptional period) have discernible programming effects that increase vulnerability to develop metabolic perturbations, the impact and eventual mechanisms involved, of such developmental alterations on the reproductive phenotype of offspring have received less attention. OBJECTIVE AND RATIONALE: This review will summarize recent advances in basic and clinical research that support the concept of DOHaD in the context of the impact of nutritional and hormonal perturbations, occurring during the periconceptional, fetal and early postnatal stages, on different aspects of reproductive function in both sexes. Special emphasis will be given to the effects of early nutritional stress on the timing of puberty and adult gonadotropic function, and to address the underlying neuroendocrine pathways, with particular attention to involvement of the Kiss1 system in these reproductive perturbations. The implications of such phenomena in terms of reproductive medicine will also be considered. SEARCH METHODS: A comprehensive MEDLINE search, using PubMed as main interface, of research articles and reviews, published mainly between 2006 and 2021, has been carried out. Search was implemented using multiple terms, focusing on clinical and preclinical data from DOHaD studies, addressing periconceptional, gestational and perinatal programming of reproduction. Selected studies addressing early programming of metabolic function have also been considered, when relevant. OUTCOMES: A solid body of evidence, from clinical and preclinical studies, has documented the impact of nutritional and hormonal fluctuations during the periconceptional, prenatal and early postnatal periods on pubertal maturation, as well as adult gonadotropic function and fertility. Furthermore, exposure to environmental chemicals, such as bisphenol A, and maternal stress has been shown to negatively influence pubertal development and gonadotropic function in adulthood. The underlying neuroendocrine pathways and mechanisms involved have been also addressed, mainly by preclinical studies, which have identified an, as yet incomplete, array of molecular and neurohormonal effectors. These include, prominently, epigenetic regulatory mechanisms and the hypothalamic Kiss1 system, which likely contribute to the generation of reproductive alterations in conditions of early nutritional and/or metabolic stress. In addition to the Kiss1 system, other major hypothalamic regulators of GnRH neurosecretion, such as γ-aminobutyric acid and glutamate, may be targets of developmental programming. WIDER IMPLICATIONS: This review addresses an underdeveloped area of reproductive biology and medicine that may help to improve our understanding of human reproductive disorders and stresses the importance, and eventual pathogenic impact, of early determinants of puberty, adult reproductive function and fertility.


Assuntos
Kisspeptinas , Medicina Reprodutiva , Adulto , Feminino , Fertilidade , Humanos , Masculino , Gravidez , Saúde Reprodutiva , Maturidade Sexual
20.
Toxins (Basel) ; 14(2)2022 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-35202133

RESUMO

The aim of this study was to determine whether low doses of zearalenone (ZEN) influence the carry-over of ZEN and its metabolites to the bone marrow microenvironment and, consequently, haematological parameters. Pre-pubertal gilts (with a body weight of up to 14.5 kg) were exposed to daily ZEN doses of 5 µg/kg BW (group ZEN5, n = 15), 10 µg/kg BW (group ZEN10, n = 15), 15 µg/kg BW (group ZEN15, n = 15), or were administered a placebo (group C, n = 15) throughout the entire experiment. Bone marrow was sampled on three dates (exposure dates 7, 21, and 42-after slaughter) and blood for haematological analyses was sampled on 10 dates. Significant differences in the analysed haematological parameters (WBC White Blood Cells, MONO-Monocytes, NEUT-Neutrophils, LYMPH-Lymphocytes, LUC-Large Unstained Cells, RBC-Red Blood Cells, HGB-Haemoglobin, HCT-Haematocrit, MCH-Mean Corpuscular Volume, MCHC-Mean Corpuscular Haemoglobin Concentrations, PLT-Platelet Count and MPV-Mean Platelet Volume) were observed between groups. The results of the experiment suggest that exposure to low ZEN doses triggered compensatory and adaptive mechanisms, stimulated the local immune system, promoted eryptosis, intensified mycotoxin biotransformation processes in the liver, and produced negative correlations between mycotoxin concentrations and selected haematological parameters.


Assuntos
Medula Óssea/efeitos dos fármacos , Plasma/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Feminino , Testes Hematológicos , Nível de Efeito Adverso não Observado , Maturidade Sexual , Suínos
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