Stage-Specific Roles for Tet1 and Tet2 in DNA Demethylation in Primordial Germ Cells

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Highlights? PGCs differentiated from ESCs undergo genome-wide DNA demethylation ? Tet1 and Tet2 do not regulate genome-wide DNA demethylation in PGCs ? Tet1 and Tet2 regulate locus-specific demethylation in PGCs     

Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion

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Highlights? EGCs can erase DNA methylation at ICRs in somatic cells after fusion ? EGCs selectively induce 5hmC accumulation at ICRs in the somatic genome ? Conversion of 5mC to 5hmC at these imprinted domains requires Tet1 ? Tet2 depletion results in delayed reprogramming by EGCs     

Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging

Female reproductive capacity declines dramatically in the fourth decade of life as a result of an age‐related decrease in oocyte quality and quantity. The primary causes of reproductive aging and the molecular factors responsible for decreased oocyte quality remain elusive. Here, we show that aging of the female germ line is accompanied by mitochondrial dysfunction associated with decreased oxidative phosphorylation and reduced Adenosine tri‐phosphate (ATP) level. Diminished expression of the enzymes responsible for CoQ production, Pdss2 and Coq6, was observed in oocytes of older females in both mouse and human. The age‐related decline in oocyte quality and quantity could be reversed by the administration of CoQ10. Oocyte‐specific disruption of Pdss2 recapitulated many of the mitochondrial and reproductive phenotypes observed in the old females including reduced ATP production and increased meiotic spindle abnormalities, resulting in infertility. Ovarian reserve in the oocyte‐specific Pdss2‐deficient animals was diminished, leading to premature ovarian failure which could be prevented by maternal dietary administration of CoQ10. We conclude that impaired mitochondrial performance created by suboptimal CoQ10 availability can drive age‐associated oocyte deficits causing infertility.     

Life-history theory, fertility and reproductive success in humans

According to life-history theory, any organism that maximizes fitness will face a trade-off between female fertility and offspring survivorship. This trade-off has been demonstrated in a variety of species, but explicit tests in humans have found a positive linear relationship between fitness and fertility. The failure to demonstrate a maximum beyond which additional births cease to enhance fitness is potentially at odds with the view that human fertility behaviour is currently adaptive. Here we report, to our knowledge, the first clear evidence for the predicted nonlinear relationship between female fertility and reproductive success in a human population, the Dogon of Mali, West Africa. The predicted maximum reproductive success of 4.1+/-0.3 surviving offspring was attained at a fertility of 10.5 births. Eighty-three per cent of the women achieved a lifetime fertility level (7-13 births) for which the predicted mean reproductive success was within the confidence limits (3.4 to 4.8) for reproductive success at the optimal fertility level. Child mortality, rather than fertility, was the primary determinant of fitness. Since the Dogon people are farmers, our results do not support the assumptions that: (i) contemporary foragers behave more adaptively than agriculturalists, and (ii) that adaptive fertility behaviour ceased with the Neolithic revolution some 9000 years ago. We also present a new method that avoids common biases in measures of reproductive success.     

Microsporogenesis,reproductive behavior,and fertility in five Pennisetum species

Summary Microsporogenesis, reproductive behavior, pollen fertility and seed set were studied in Pennisetum basedowii Summerhayes and C. E. Hubbard, 2n = 54; P. macrostachyum (Brough.) Trin., 2n = 54; P. macrourum Trin., 2n = 36; P. polystachion (L.) Schult, 2n = 54; and P. squamulatum Fresen 2n = 54. Meiosis was regular in P. basedowii with primarily bivalent pairing. As many as 54 univalents were observed at metaphase I in P. macrostachyum. A high frequency of univalents at metaphase I in P. macrourum resulted in lagging chromosomes and micronuclei at anaphase I and telophase I, respectively. Pennisetum polystachion and P. squamulatum showed frequent multivalent chromosome associations. Studies of megasporogenesis and embryo sac development in P. basedowii showed sexual reproduction. Pennisetum macrostachyum was highly male sterile with predominantly aposporous apomictic embryo sac development. Pennisetum macrourum, P. polystachion, and P. squamulatum had only aposporous embryo sac development. Seed propagated progenies of these latter three species were uniform and matromorphic, confirming the obligate apomixis nature.     

Cohesion介导的减数分裂异常与卵子老化发生的关系

社会发展及计划生育政策的顺势改变,使得高龄女性的生育需求不断扩大,但与年龄相关的卵子老化是高龄女性急需解决的生育难题,而造成卵子老化的主因确是卵母细胞非整倍体发生率的增加.粘连蛋白(cohesin)能够介导姐妹染色单体之间的着丝粒凝聚力从而稳定二价染色体结构,cohesin介导的减数分裂异常与卵子老化的发生关系密切,以...     

A model of fertility motivation, desires, and expectations early in women's reproductive careers

We propose a general model of the relationships connecting fertility motivations, desires, and expectations in which motivations are antecedent to desires, which in turn are antecedent to expectations. We describe differences in the model as it applies to women early in their reproductive careers, specifically, after marriage but before their 1st birth and after their 1st birth but before their 2nd. We test the model with data from 311 just-married and 318 just-mothered US women enrolled in a prospective psychology of reproduction study, using LISREL (analysis of linear structural relationships by the method of maximum likelihood) software to estimate structural equations for both groups. The general model fits the data well. There are 3 primary differences in the model with respect to the 2 groups of married women. How soon a woman expects her next child affects how many children she expects only among the just-married woman. The number of children expected by the woman is the only antecedent to how soon she expects her next child among the just-mothered women. Both positive and negative maternal motivation has effects among the just-married women, but only negative maternal motivation has effects among the just-mothered women. These and other differences are discussed in terms of psychological and situational developments occurring early in women's reproductive careers.     

A model of fertility motivation,desires, and expectations early in women's reproductive careers

Abstract

We propose a general model of the relationships connecting fertility motivations, desires, and expectations in which motivations are antecedent to desires, which in turn are antecedent to expectations. We describe differences in the model as it applies to women early in their reproductive careers, specifically, after marriage but before their first birth and after their first birth but before their second. We test the model with data from 311 just‐married and 318 just‐mothered women, using LISREL to estimate structural equations for both groups. The general model fits the data well. There are three primary differences in the model with respect to the two groups of married women. How soon a woman expects her next child affects how many children she expects only among the just‐married woman. The number of children expected by the woman is the only antecedent to how soon she expects her next child among the just‐mothered women. Both positive and negative maternal motivation has effects among the just‐married women, but only negative maternal motivation has effects among the just‐mothered women. These and other differences are discussed in terms of psychological and situational developments occurring early in women's reproductive careers.     

Leptin regulation of reproductive function and fertility.

Leptin, a 16-KD protein secreted primarily by adipose tissue, was first discovered in the search for a satiety signal. When administered into the brain, leptin depresses appetite. Interestingly, hyperphagic, obese, transgenic mice with leptin deficiency were noted to be reproductively incompetent, and administration of leptin restored their fertility. These pivotal observations led to numerous studies on the site of action of leptin within the hypothalamo-hypophyseal-gonadal axis, and a variety of models have been used ranging from the prepubertal condition to fasting suppression of reproductive hormones. The preponderance of studies thus far has focused on how leptin serves as a metabolic signal of energy balance within the neuroendocrine system, particularly as a regulator of GnRH/LH secretion. Less research has been conducted with other components of the reproductive system, but local effects of leptin have been demonstrated in the gonads where hyperleptinemia suppresses steroidogenesis and potentially affects gamete maturation. This presentation will review the major concepts for the role of leptin in the modulation of fertility and will consider the potential use of leptin in assisted reproductive technology and embryo transfer.     

Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells

TET family enzymes convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. Here, we show that Tet1 and Tet2 are Oct4-regulated enzymes that together sustain 5hmC in mouse embryonic stem cells (ESCs) and are induced concomitantly with 5hmC during reprogramming of fibroblasts to induced pluripotent stem cells. ESCs depleted of Tet1 by RNAi show diminished expression of the Nodal antagonist Lefty1 and display hyperactive Nodal signaling and skewed differentiation into the endoderm-mesoderm lineage in embryoid bodies in?vitro. In Fgf4- and heparin-supplemented culture conditions, Tet1-depleted ESCs activate the trophoblast stem cell lineage determinant Elf5 and can colonize the placenta in midgestation embryo chimeras. Consistent with these findings, Tet1-depleted ESCs?form aggressive hemorrhagic teratomas with increased endoderm, reduced neuroectoderm, and ectopic appearance of trophoblastic giant cells. Thus, 5hmC is an epigenetic modification associated with the pluripotent state, and Tet1 functions to regulate the lineage differentiation potential of ESCs.     

Production, reproductive, and metabolic factors associated with chlamydial seropositivity and reproductive tract antigens in dairy herds with fertility disorders

While chlamydial infections cause abortions in cattle, its role in other reproductive disorders is uncertain. This study identified the risk factors for chlamydial infection in herds with history of subfertility. We investigated the possible effects of coinfections, different metabolic parameters, abortion, ovarian cysts, pathological vaginal discharge, length of the open period, milk yield, housing conditions and age. In cows from 34 farms with elevated reproductive disorders, 41.5% had antibodies against chlamydia, while chlamydia antigen was detected in the vagina and uterus of 46.7%. A statistical relationship between seropositivity and antigen positivity was not found. Abortion (OR = 6.6) and loose housing (OR = 2.3) were risk factors for the presence of chlamydia antibodies. Furthermore, there were significant relationships between metabolic disorders and chlamydial infections. Increased levels of beta-hydroxybutaric acid (OR = 6.8) and hypocalcaemia (OR = 6.0) often accompanied chlamydia antigen in the vagina. Increased age (OR = 1.2) and pathological vaginal discharge (OR = 2.4) were identified as risk factors for chlamydia antigen in the vagina. The largest risk factor was for the association of ovarian cysts (OR = 21.5) with uterine antigen. In conclusion, chlamydial infection in dairy herd cows is best understood as a multifactorial disease.     

Mechanisms of reproductive aging in the females

Aging is a developmental process occurring in all living organisms after reaching a critical developmental stage, characterized by progressive loss of functions until death. Different cells/tissues age differently depending on epigenetics and cell-cell interactions. While males maintain fertility for the most part of their life females only maintain reproductive ability for a short time compared with their lifespan. The interesting question is why and how the females lose fertility so quickly. There have been many hypotheses proposed from different perspectives and recent research has revealed unusual interactions between germ cells and somatic cells which may determine the lifespan of reproduction in the females. This review briefly discusses recent progress in reproductive aging in the well studied model, C. elegans, and focuses on the molecular mechanisms which may be conserved across all animals including humans.     

Fecundity,fertility and reproductive recovery of irradiated Queensland fruit fly Bactrocera tryoni

Pupae of the Queensland fruit fly or Q‐fly Bactrocera tryoni (Froggatt) are irradiated routinely to induce reproductive sterility in adults for use in sterile insect technique programmes. Previous studies suggest that adult sexual performance and survival under nutritional and crowding stress are compromised by the current target dose of radiation for sterilization (70–75 Gy), and that improved mating propensity and survival under stress by irradiated males may be achieved by reducing the target sterilization dose without reducing the level of induced sterility. This raises the question of the amount by which the irradiation dose can be reduced before residual fertility becomes unacceptable. The present study measures the levels of residual fertility in male and female irradiated Q‐flies at different irradiation doses (20, 30, 40, 50, 60 and 70 Gy), and investigates the possibility that fecundity and fertility increase between 10–15 and 30–35 days post emergence. Male flies require a higher dose than females to induce sterility, with no residual fertility found in females irradiated at doses of 50 Gy or above, and no residual fertility found in males irradiated at doses of 60 Gy or above. Irradiated females are more fecund at 30–35 days post emergence than at 10–15 days. However, fertility does not increase between 10 and 15 days post emergence and 30–35 days, even at doses below 50 Gy. The present study shows that there is scope to reduce the target sterilization dose for Q‐flies below that of the current dose range (70–75 Gy) at the same time as retaining an adequate safety margin above radiation doses at which residual fertility can be expected.     

Mitotic behavior of centromeres in meiosis as the fertility restoration mechanism in wheat-rye amphihaploids

The regulation of chromosomal behavior in meiosis in partly fertile wheat-rye amphihaploids was studied using the centromere specific probes pAWRC1 and Ae. tauschii pAet6-09. Comparative analysis of the probe localization patterns in mitosis, normal meiosis in wheat Triticum aestivum L. and rye Secale cereale L., and meiosis in amphihaploids was performed. The differences in the structure of centromeres in monopolar- and bipolaroriented chromosomes were revealed. Single dense hybridization signals were observed in the diplotene and the metaphase of the first meiotic division, while hybridization signals appeared as stretched bands with diffuse structure located across the centromere region in mitosis and the second round of meiotic division. Based upon the obtained data, we used the corresponding centromere-specific probes as a tool for the analysis of chromosomal behavior in meiosis in amphihaploids. In meiocytes with three types of chromosome behavior (reductional, equational plus reductional, and equational), dense point-like hybridization signals for the pAet6-09 probe were observed for univalents with the reductional division type and stretched bands with diffuse structure for those with the equational division type. Thus, pAet6-09 probe localization patterns suggest some structural and functional specificities of centromeres in the meiosis in wheat-rye amphihaploids that reflect special regulation of chromosomal behavior during equational division. Meiocytes with true mitotic division were also observed in anthers predominantly containing meiocytes with chromosomes undergoing equational division.