Intrafollicular conditions as a major link between maternal metabolism and oocyte quality: a focus on dairy cow fertility

2012 ◽  
Vol 24 (1) ◽  
pp. 1 ◽  
Author(s):  
J. L. M. R. Leroy ◽  
D. Rizos ◽  
R. Sturmey ◽  
P. Bossaert ◽  
A. Gutierrez-Adan ◽  
...  
Keyword(s):  
Dairy Cows ◽  
Embryo Quality ◽  
Ovarian Follicle ◽  
Oocyte Quality ◽  
Developmental Competence ◽  
Metabolic Disturbances ◽  
Oocyte Growth ◽  
Adverse Conditions ◽  
Maternal Metabolism

Reduced oocyte and embryo quality are recognised as major factors in the problem of disappointing fertility in high producing dairy cows. This review aims to shed more light on the importance of the intrafollicular environment in the subfertility problem in dairy cows. Metabolic disturbances associated with negative energy balance (NEB) early postpartum are associated with ovarian dysfunction. Changes in the growth pattern of the ovarian follicle during a period of NEB can indirectly affect oocyte quality. Furthermore, a maternal metabolic disorder (linked with NEB or nutritionally induced) may alter the endocrine and biochemical composition of the follicular fluid, the micro-environment of the growing and maturing female gamete. The maturing oocyte is very sensitive to any perturbation in its direct environment and in vitro maturation models revealed that some of these metabolic changes reduce the oocyte’s developmental competence. Also, embryo quality is significantly reduced due to maturation in adverse conditions. Well balanced and timed oocyte metabolism and gene expression are crucial to safeguard an optimal oocyte development. In that perspective, metabolome and transcriptome parameters of the oocyte may serve to predict reproductive success rates. Finally, there is growing evidence that adverse conditions for oocyte growth and maturation may also jeopardise the health and performance of the offspring.

In vitro Culture of Early Secondary Preantral Follicles to Obtain MII Oocyte Developmental Competence from CD-1 Outbred Mice

2020 ◽  
Author(s):  
Jongwon Kim ◽  
Seungki Lee ◽  
Jung Kyu Choi
Keyword(s):  
In Vitro Culture ◽  
Culture System ◽  
Ovarian Follicle ◽  
Oocyte Quality ◽  
Developmental Competence ◽  
Vitro Fertilization ◽  
Preantral Follicles ◽  
Successful Isolation ◽  
In Vitro Culture System

Background: The ovarian follicle is the fundamental functional tissue unit that consists of mammalian ovary. In humans, it has been known that females are born with a maximum number of follicles or oocytes that are not only non-renewable, but also undergoing degeneration with time with a sharply decreased oocyte quality after the age of 35. Methods: Here, we demonstrate that successful isolation of primary, early secondary and late secondary follicles from the ovaries of CD-1 outbred female mice and in vitro culture system to successfully induce the development of MII oocytes. Result: The 9 days of in vitro culture of early secondary follicles showed significant higher rates in growth and maturation displaying higher numbers of antral follicles and MII oocytes developed from early secondary follicles compared to those cultured for 11 days. However, there was no visible difference induced by the size of initial follicles in the rates of growth and maturation. MII oocytes derived from in vitro culture of early secondary follicles following in vitro fertilization developed into two-cell embryos. These observations demonstrate that developmentally competent MII oocytes can be obtained by in vitro culture of preantral follicles derived from the ovaries of CD-1 mice and reveal a crucial role for CD-1 mice as a novel model for research on human ovarian follicles. Furthermore, this study proposes an in vitro culture system using preantral follicle as a therapeutic strategy for fertility preservation of humans for assisted reproductive medicine. 

scholarly journals Cyclophosphamide Exposure Causes Long-Term Detrimental Effect of Oocytes Developmental Competence Through Affecting the Epigenetic Modification and Maternal Factors’ Transcription During Oocyte Growth

2021 ◽  
Vol 9 ◽  
Author(s):  
Weijie Yang ◽  
Yerong Ma ◽  
Jiamin Jin ◽  
Peipei Ren ◽  
Hanjing Zhou ◽  
...  
Keyword(s):  
Dna Damage ◽  
Culture Media ◽  
Epigenetic Modification ◽  
Primordial Follicle ◽  
Oocyte Quality ◽  
Mature Oocyte ◽  
Developmental Competence ◽  
Oocyte Growth ◽  
Primordial Follicles

Cyclophosphamide (CTX) is widely used in various cancer therapies and in immunosuppression, and patients can still have babies after CTX chemotherapy. CTX directly causes primordial follicle loss with overactivation and DNA damage-induced apoptosis. Previous studies have shown that maternal exposure to CTX before conception increases the incidence of birth abnormalities and alters the methylation of genes in the oocytes of offspring. Mice were treated with a single dose of CTX (100 mg/kg) at post-natal day 21 and sacrificed 47 days later when primordial follicles surviving chemotherapy developed to the antral stage. Acute DNA damage and acceleration of the activation of primordial follicles after CTX treatment were repaired within several days, but the remaining follicle numbers remarkably decrease. Although partial surviving primordial follicle were developed to mature oocyte, oocyte quality hemostasis was impaired exhibiting aberrant meiosis progression, abnormal spindle and aneuploidy, mitochondrial dysfunction and increased endoplasmic reticulum stress. Thereafter, embryo development competency significantly decreased with fewer blastocyst formation after CTX exposure. CTX treatment resulted in alteration of DNA methylations and histone modifications in fully grown GV oocytes. Single-cell RNA-seq revealed CTX treatment suppressed multiple maternal genes’ transcription including many methyltransferases and maternal factor YAP1, which probably accounts for low quality of CTX-repaired oocyte. In vitro addition of lysophosphatidic acid (LPA) to embryo culture media to promote YAP1 nuclear localization improved CTX-repaired embryo developmental competence. This study provides evidence for the consistent toxic effect of CTX exposure during follicle development, and provide a new mechanism and new insights into future clinical interventions for fertility preservation.

26 Season affects cryotolerance of in vitro-produced buffalo embryos

2019 ◽  
Vol 31 (1) ◽  
pp. 139 ◽  
Author(s):  
M. A. Kosior ◽  
E. Parente ◽  
F. Salerno ◽  
K. Annes ◽  
R. Annunziata ◽  
...  
Keyword(s):  
Developmental Stage ◽  
Breeding Season ◽  
Embryo Quality ◽  
Sucrose Solution ◽  
Oocyte Quality ◽  
Developmental Competence ◽  
Seasonal Effect ◽  
Morphological Criteria ◽  
Breeding Seasons

Buffaloes are tendentially short-day breeders, and seasonality is one of the main factors affecting the feasibility of ovum pickup and in vitro embryo production technology in this species. An improvement of oocyte developmental competence during decreasing daylight months was previously reported in Italian Mediterranean buffalo (Di Francesco et al. 2011 Anim. Reprod. Sci. 123, 48-53). The aim of this work was to evaluate whether season also affects embryo quality and cryotolerance. Abattoir-derived buffalo cumulus-oocyte complexes were collected during the breeding season, characterised by decreasing daylight length (n=349 over 6 replicates), and the non-breeding season, characterised by increasing daylight length (n=770 over 12 replicates). Buffalo cumulus-oocyte complexes were in vitro matured, fertilized, and cultured according to standard procedures (Di Francesco et al. 2011 Anim. Reprod. Sci. 123, 48-53). The embryos obtained by the end of culture (i.e. on Day 7 post-IVF) were scored for quality and developmental stage, and the percentages of total transferable embryos (tight morulae and blastocysts) were recorded. Embryos (n=107 and 110 in the breeding and non-breeding seasons, respectively) were vitrified by cryotop in 16.5% ethylene glycol, 16.5% dimethyl sulfoxide, and 0.5M sucrose (Boccia et al. 2013 Ital. J. Anim. Sci. 12, 492-496). Warming was carried out by plunging the cryotop strip into a 0.25M sucrose solution and transferring the embryos into 0.15M sucrose for 5min. Embryos were then washed and cultured in SOF for 24h to evaluate post-culture viability. The resistance to cryopreservation was evaluated by assessing the survival rate, on the basis of morphological criteria, and development rate (i.e. the percentage of embryos that resumed their development and reached a more advanced developmental stage) after 24h post-warming culture. Data were analysed by Student’s t-test. Both cleavage (82.8±4.3v. 73.1±1.7 in the breeding and non-breeding seasons, respectively; P<0.05) and blastocyst (32.9±3.5v. 18.3±1.7 in the breeding and non-breeding seasons, respectively; P<0.01) rates increased during the breeding season, confirming previous observations. Due to the different efficiency, a higher number of replicates was required during the non-breeding season to obtain an equal number of embryos. In addition, a seasonal effect was recorded on embryo quality, indicated by poorer cryotolerance of in vitro-produced buffalo embryos during the non-breeding season. Indeed, both survival (94.6±2.7% and 74.0±5.5% in the breeding and non-breeding seasons, respectively; P<0.01) and development (67.3±7.6% and 40.0±7.2% in the breeding and non-breeding seasons, respectively; P<0.01) rates of vitrified blastocysts decreased after 24h post-warming culture in the non-breeding season. These findings suggest that the reduced developmental competence of buffalo oocytes during the non-breeding season may also lead to lower blastocyst quality. This is in contrast to the evidence in cattle that embryo quality is mainly determined by culture conditions, whereas blastocyst production depends on oocyte quality.

Reversing complete mechanical transzonal projections disruption during mouse in vitro follicle culture with unaltered oocyte competence

2021 ◽  
Author(s):  
Anamaria-Cristina Herta ◽  
Nazli Akin ◽  
Katy Billooye ◽  
Laura Saucedo-Cuevas ◽  
Francesca Lolicato ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Oocyte Quality ◽  
Mature Oocyte ◽  
Developmental Competence ◽  
Human Oocyte ◽  
Oocyte Growth ◽  
Follicle Culture ◽  
Oocyte Competence ◽  
The Impact

Abstract In vitro oocyte growth is widely studied as an alternative fertility preservation approach. Several animal models are used to generate extensive information on this complex process regulated by the constant and dynamic interaction between the oocyte and its somatic compartment throughout follicle growth and maturation. A 2-dimensional (2D) attachment mouse secondary follicle culture system was used to assess the oocyte’s capacity to overcome disconnection from its somatic companions at different developmental stages for final competence acquisition. To test this, complete mechanical denudation of oocytes from preantral and early antral follicles was performed. Established endpoints were the oocyte’s potential to reconnect with somatic cells and the impact of connectivity disruption on mature oocyte quality. This study proves that oocytes from preantral and early antral cultured mouse follicles can overcome complete denudation, restoring likely functional transzonal projections (TZPs) with no significant differences in meiotic and developmental competence compared to those from intact cultured follicles. These novel findings constitute good premises for developing successful strategies to rescue human oocyte competence in the context of in vitro culture approaches such as non-hCG triggered in vitro maturation (IVM).

scholarly journals Molecular evidence that follicle development is accelerated in vitro compared to in vivo

Reproduction ◽  
2017 ◽  
Vol 153 (5) ◽  
pp. 493-508 ◽  
Author(s):  
Véronique Cadoret ◽  
Cynthia Frapsauce ◽  
Peggy Jarrier ◽  
Virginie Maillard ◽  
Agnès Bonnet ◽  
...  
Keyword(s):  
Granulosa Cell ◽  
Ovarian Follicle ◽  
Three Dimensional ◽  
Developmental Competence ◽  
Molecular Characteristics ◽  
Molecular Evidence ◽  
Follicle Development ◽  
Oocyte Growth

In this study, we systematically compared the morphological, functional and molecular characteristics of granulosa cells and oocytes obtained by a three-dimensional in vitro model of ovine ovarian follicular growth with those of follicles recovered in vivo. Preantral follicles of 200 µm diameter were recovered and cultured up to 950 µm over a 20-day period. Compared with in vivo follicles, the in vitro culture conditions maintained follicle survival, with no difference in the rate of atresia. However, the in vitro conditions induced a slight decrease in oocyte growth rate, delayed antrum formation and increased granulosa cell proliferation rate, accompanied by an increase and decrease in CCND2 and CDKN1A mRNA expression respectively. These changes were associated with advanced granulosa cell differentiation in early antral follicles larger than 400 µm diameter, regardless of the presence or absence of FSH, as indicated by an increase in estradiol secretion, together with decreased AMH secretion and expression, as well as increased expression of GJA1, CYP19A1, ESR1, ESR2, FSHR, INHA, INHBA, INHBB and FST. There was a decrease in the expression of oocyte-specific molecular markers GJA4, KIT, ZP3, WEE2 and BMP15 in vitro compared to that in vivo. Moreover, a higher percentage of the oocytes recovered from cultured follicles 550 to 950 µm in diameter was able to reach the metaphase II meiosis stage. Overall, this in vitro model of ovarian follicle development is characterized by accelerated follicular maturation, associated with improved developmental competence of the oocyte, compared to follicles recovered in vivo.

P–219 mtDNA content in bovine cumulus cells does not predict oocytés developmental competence

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Á Martíne. Moro ◽  
I Lamas-Toranzo ◽  
L González-Brusi ◽  
A Pérez-Gómez ◽  
P Bermejo-Álvarez
Keyword(s):  
Cumulus Cell ◽  
Cumulus Cells ◽  
Oocyte Quality ◽  
Blastocyst Stage ◽  
Early Embryo ◽  
Developmental Competence ◽  
Success Rates ◽  
Developmental Potential ◽  
Mtdna Sequence

Abstract Study question Does cumulus cell mtDNA content correlate with oocyte developmental potential in the bovine model? Summary answer The relative amount of mtDNA content did not vary significantly in oocytes showing different developmental outcomes following IVF What is known already Cumulus cells are closely connected to the oocyte through transzonal projections, serving essential metabolic functions during folliculogenesis. These oocyte-supporting cells are removed and discarded prior to ICSI, thereby constituting an interesting biological material on which to perform molecular analysis aimed to predict oocyte developmental competence. Previous studies have positively associated oocytés mtDNA content with developmental potential in both animal models and women. However, it remains debatable whether mtDNA content in cumulus cells could be used as a proxy to infer oocyte developmental potential. Study design, size, duration Bovine cumulus cells were allocated into three groups according to the developmental potential of the oocyte: 1) oocytes developing to blastocysts following IVF (Bl+Cl+), 2) oocytes cleaving following IVF but arresting their development prior to the blastocyst stage (Bl-Cl+), and 3) oocytes not cleaving following IVF (Bl-Cl-). Relative mtDNA content was analysed in 40 samples/group, each composed by the cumulus cells from one cumulus-oocyte complex (COC). Participants/materials, setting, methods Bovine cumulus-oocyte complexes were obtained from slaughtered cattle and individually matured in vitro (IVM). Following IVM, cumulus cells were removed by hyaluronidase treatment, pelleted, snap frozen in liquid nitrogen and stored at –80 ºC until analysis. Cumulus-free oocytes were fertilized and cultured in vitro individually and development was recorded for each oocyte. Relative mtDNA abundance was determined by qPCR, amplifying a mtDNA sequence (COX1) and a chromosomal sequence (PPIA). Statistical differences were tested by ANOVA. Main results and the role of chance Relative mtDNA abundance did not differ significantly (ANOVA p > 0.05) between the three groups exhibiting different developmental potential (1±0.06 vs. 1.19±0.05 vs. 1.11±0.05, for Bl+Cl+ vs. Bl-Cl+ vs. Bl-Cl-, mean±s.e.m.). Limitations, reasons for caution Experiments were conducted in the bovine model. Although bovine folliculogenesis, monoovulatory ovulation and early embryo development exhibit considerable similarities with that of humans, caution should be taken when extrapolating these data to humans. Wider implications of the findings: The use of molecular markers for oocyte developmental potential in cumulus cells could be used to enhance success rates following single-embryo transfer. Unfortunately, mtDNA in cumulus cells was not found to be a good proxy for oocyte quality. Trial registration number Not applicable

P–458 A computational biology approach to improve in-vitro folliculogenesis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C D Berardino ◽  
N Bernabò ◽  
G Capacchietti ◽  
A Peserico ◽  
G Buoncuore ◽  
...  
Keyword(s):  
Metabolic Control ◽  
Intracellular Signaling ◽  
Assisted Reproductive Technologies ◽  
Computational Modelling ◽  
Reproductive Technologies ◽  
Developmental Competence ◽  
Paracrine Factors ◽  
Oocyte Growth ◽  
Topological Parameters

Abstract Study question Considering the complexity of mechanisms involved in mammalian ovarian folliculogenesis, how about improving the current in-vitro folliculogenesis (ivF) protocols to prolong individual reproductive chance? Summary answer Computational modelling approach based on network theory was used to manage complexity, improve ivF knowledge and discover new molecules to be targeted for innovating assisted-reproductive-technologies. What is known already: Over the past decades, based on the large ovarian-pool of immature-gametes availability, ivF systems were developed in several mammalian species to support oocyte growth in order to preserve human-fertility and contrast endangered species extinction. Only mouse live-births were obtained when primordial/primary follicles were cultured in-vitro, instead the oocyte differentiation is extremely slow in medium-sized mammals. Moreover, the degree of meiotic-competence is quite incomplete if compared to mice, because oocytes must proceed until late antral-follicle stage to acquire a complete developmental competence. These observations denote the importance to adopt further investigations for establishing a complete ivF protocol in translational mammal model. Study design, size, duration Two researchers expert on reproductive biology generated the Web of Science-Mammals-Made in-vitro folliculogenesis (WoS_MMivF) database including 1111 manuscripts published in peer-reviewed international papers indexed selected in Advanced Search of WoS “Core-collection” by carrying out an independent analysis. Two additional researchers verified the correctness of the records. Participants/materials, setting, methods WoS_MMivF network was built up using Cytoscape 2.6.3 software. The network was analyzed for topological parameters (closeness-centrality, betweenness-centrality and edge count) and to identify key controllers (Hub.BN). Bidimensional-kernel-density-estimation (2D KDE) identifies Hub.BN controllers; Search-Tool-for-the-Retrieval-of-Interacting-Genes/Proteins (STRING) were used to enrich the network with new proteins. Main results and the role of chance The analysis of topological parameters demonstrated that the network is scale-free according to Barabási-Albert-model with a high-degree of robustness-against-random-damage, great controllability and navigability. The network reproduces a coherent framework identifying cross-talking molecules playing a key role in the inter-follicular/intra (somatic and germinal compartment) dialogue. The network allows to organize signalling transduction events/molecules by stratifying them in three layers: input-layer recognizes molecules generating the information flux working as systemic endocrine (pituitary/chorion/enteric-related endocrine hormones) and local paracrine-factors (TGFbeta-superfamily-members and growth-factors) exerting either intrafollicular control or remote feedback on reproductive-cycle. Processing-layer presents molecules able to elaborate/amplify the endocrine/paracrine controllers of ovarian functions, including components of codified intracellular-signaling-pathways like PI3K, KIT and MAPK and second messengers cAMP and Ca2+. These cascades are necessary to promote in-vitro reproducible follicular functions and modulate steroidogenesis, representing molecular events stratified in the output-layer. STRING analysis allowed to extend the regulatory flow of information towards two major biological action contexts: metabolic-control (paracrine-factors and signal-transduction) and angiogenesis. Metabolic-control mediated by mTOR and its interactor cognates FOXO1, FOXO3/SIRT1 plays a key role for ivF, representing the energy sensors of the reproductive cells in hypothalamic-pituitary-ovarian-axis first regulating the status of follicle quiescence/activation and then fate of the structure (specialization or apoptosis). Limitations, reasons for caution - Wider implications of the findings: STRING identified mTOR as key pathway of folliculogenesis, which might act as a molecular-switch to be pharmacologically targeted for potential new in-vitro strategies modulating follicular fate. These results suggest that computational approach in biology might offer perspective in identifying unknown signals, implementing research questions and innovative protocols to face female-fertility. Trial registration number Not applicable

scholarly journals Cytoplasmic Transfer Improves Human Egg Fertilization and Embryo Quality: an Evaluation of Sibling Oocytes in Women with Low Oocyte Quality

2020 ◽  
Author(s):  
Ales Sobek ◽  
Emil Tkadlec ◽  
Eva Klaskova ◽  
Martin Prochazka
Keyword(s):  
Embryo Quality ◽  
Oocyte Quality ◽  
Fertilization Rate ◽  
Early Embryo ◽  
Vitro Fertilization ◽  
Sibling Oocytes ◽  
Fertilization Rates ◽  
Group B ◽  
Cytoplasmic Transfer

Abstract The aim of this study was to evaluate if cytoplasmic transfer can improve fertilization and embryo quality of women with oocytes of low quality. During ICSI, 10–15% of the cytoplasm from a fresh or frozen young donor oocyte was added to the recipient oocyte. According to the embryo quality, we defined group A as patients in which the best embryo was evident after cytoplasmic transfer and group B as patients in which the best embryo was evident after a simple ICSI. We investigated in the period of 2002–2018, 125 in vitro fertilization cycles involving 1011 fertilized oocytes. Five hundred fifty-seven sibling oocytes were fertilized using ICSI only and 454 oocytes with cytoplasmic transfer. Fertilization rates of oocytes were 67.2% in the cytoplasmic transfer and 53.5% in the ICSI groups (P < 0.001). A reduction in fertilization rate was observed with increased women age in the ICSI but not in the cytoplasmic transfer groups. The best embryo quality was found after cytoplasmic transfer in 78 cycles (62.4%) and without cytoplasmic transfer in 40 cycles (32%, P < 0.001). No significant differences were detected between the age, hormonal levels, dose of stimulation drugs, number of transferred embryos, pregnancy rate and abortion rate between A and B groups. Cytoplasmic transfer improves fertilization rates and early embryo development in humans with low oocyte quality. All 28 children resulting from cytoplasmic transfer are healthy.

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