The FSH–HIF-1α–VEGF Pathway Is Critical for Ovulation and Oocyte Health but Not Necessary for Follicular Growth in Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (4) ◽  
Author(s):  
Chengyu Li ◽  
Zhaojun Liu ◽  
Weijian Li ◽  
Liangliang Zhang ◽  
Jilong Zhou ◽  
...  
Keyword(s):  
Ovarian Follicle ◽  
Hypoxia Inducible Factor ◽  
Oocyte Quality ◽  
Ovarian Follicles ◽  
Actin Dynamics ◽  
Independent Effect ◽  
Follicular Growth ◽  
Growth And Survival ◽  
Ovarian Follicle Development ◽  
Antral Follicles

Abstract Follicle-stimulating hormone (FSH)-induced growth of ovarian follicles is independent of follicular vascularization. Recent evidence has indicated that follicular vascularization is critical to ovarian follicle development and survival. FSH, a gonadotropin that induces follicular growth and development, also acts as the major survival factor for antral follicles. FSH has been reported to stimulate angiogenesis in the theca layers mediated in part by the vascular endothelial growth factor A (VEGFA) and the transcription factor hypoxia inducible factor 1α (HIF-1α). However, it remains largely undetermined whether FSH-dependent growth and survival of antral follicles relies on FSH-induced vascularization. Here, we first demonstrated that induction of angiogenesis through the FSH–HIF–1α-VEGFA axis is not required for FSH-stimulated follicular growth in mouse ovary. FSH increased the total number of blood vessels in mouse ovarian follicles, which was correlated with elevated expression of VEGFA and HIF-1α in granulosa cells. In contrast, blocking of follicular angiogenesis using inhibitors against the HIF-1α-VEGFA pathway repressed vasculature formation in follicles despite FSH administration. Interestingly, by measuring follicular size and ovarian weight, we found that the suppression of angiogenesis via HIF-1α–VEGFA pathway did not influence FSH-mediated follicular growth. However, inhibition of FSH-induced follicular vascularization by PX-478, a small-molecule inhibitor that suppresses HIF-1α activity, blocked ovulation and triggered atresia in large follicles. On the other hand, PX-478 injection reduced oocyte quality via impairing the meiotic apparatus, showing a prominently defective spindle assembly and actin dynamics. Collectively, our findings unveiled a vascularization-independent effect of FSH on follicular growth, whereas follicular survival, ovulation, and oocyte development relies on FSH-mediated angiogenesis in the follicles.

Altrenogest affects the development and endocrine milieu of ovarian follicles in prepubertal and mature gilts†

2020 ◽  
Vol 103 (5) ◽  
pp. 1069-1084
Author(s):  
Adam J Ziecik ◽  
Klaudia Drzewiecka ◽  
Katarzyna Gromadzka-Hliwa ◽  
Jan Klos ◽  
Patrycja Witek ◽  
...  
Keyword(s):  
Follicular Fluid ◽  
Messenger Rna ◽  
Ovarian Follicle ◽  
Adenosine Monophosphate ◽  
Cyst Formation ◽  
Ovarian Follicles ◽  
Mrna Levels ◽  
Molecular Control ◽  
Antral Follicles ◽  
Follicular Cyst

Abstract Altrenogest with gonadotropins is commonly used to synchronize the estrous cycle, but it can also lead to follicular cyst formation, especially in prepubertal gilts. Here, we aimed to investigate how maturity and altrenogest treatment affect the development, endocrine milieu, and molecular control of ovarian follicles. Crossbred prepubertal and mature gilts were challenged or not (control) with altrenogest, and ovaries were collected in the morning on the first day of behavioral estrus. In prepubertal gilts, altrenogest decreased the percentage of primordial and atretic small follicles, but increased large antral follicles when compared with controls. In mature gilts, altrenogest reduced the percentage of primary follicles and elevated the total number of antral follicles. Maturity affected the estradiol level in the follicular fluid of preovulatory follicles, luteinizing hormone (LH)-stimulated cyclic adenosine monophosphate (cAMP) generation, and LH receptor messenger RNA (mRNA) expression in granulosa. Moreover, cytochrome P45017A1 (CYP17A1) mRNA levels in the theca layer were affected and correlated with follicular androstendione and estradiol concentration. Altrenogest negatively affected follicular fluid progesterone concentration and decreased levels of prostaglandin (PG) E2 in prepubertal gilts and PGF2alpha metabolite in mature gilts. LH-stimulated cAMP release in granulosa cells of mature gilts as well as human chorionic gonadotropin- and forskolin-induced cAMP were also affected. In addition, altrenogest downregulated CYP17A1 mRNA in the prepubertal theca layer and PGF2alpha synthase expression in the granulosa and theca layer of mature gilts. To the best of our knowledge, this is the first study to report multiple effects of maturity and altrenogest on the endocrine milieu and molecular regulations governing ovarian follicle development in gilts.

138 Relationships Between Antral Follicle Count, Ovarian Volume, Pre-Antral Follicle Number, and Oocyte Quality

2018 ◽  
Vol 30 (1) ◽  
pp. 209
Author(s):  
G. L. Vasconcelos ◽  
R. Maculan ◽  
N. Alves ◽  
A. L. A. P. L. Ribeiro ◽  
A. W. B. Silva ◽  
...  
Keyword(s):  
Ovarian Follicle ◽  
Primordial Follicle ◽  
Antral Follicle ◽  
Oocyte Quality ◽  
Antral Follicle Count ◽  
Primary Follicle ◽  
Ovarian Volume ◽  
Primordial Follicles ◽  
Antral Follicles ◽  
Grade 3

The objective was to evaluate the possible relationships between AFC, ovarian volume, ovarian follicle reserve and oocyte quality in abattoir-derived ovaries (experiment 1) and in cows (experiment 2) submitted to OPU. Antral follicle counts of ≥25, 16 to 24, and ≤ 16 were used to define AFC classes as high (HAFC), intermediate (IAFC), and low (LAFC) in both experiments. In experiment 1, after antral follicles were aspirated, abattoir ovaries (n = 10 per AFC class) were processed by conventional histology and pre-antral follicles were counted within primordial, primary, secondary, and tertiary classes and classified as either healthy or degenerate under regular microscopy (Cushman et al. 1999). In experiment 2, HAFC (n = 42), IAFC (n = 34), and LAFC (n = 29) cows were submitted to OPU and oocytes classified as grades 1, 2, and 3 or degenerate (IETS, 2010). Antral follicles (≥3 mm in diameter) were counted by ultrasonography. Data were analysed by GENMOD and GLM procedures of SAS (SAS Institute Inc., Cary, NC, USA) after transformations, when required. In experiment 1, mean normal primordial follicle number was higher (P < 0.001) in HAFC (137.0 ± 1.6)a compared with IAFC (52.6 ± 1.9)b and LAFC (20.2 ± 5.3)c ovaries. However, the mean number of degenerate primordial follicles was lower (P < 0.001) in low count ovaries (2.4 ± 0.6) compared with HAFC (19.0 ± 4.7) and IAFC (16.4 ± 1.5, P < 0.001). Normal primary follicle number was higher in the HAFC compared with IAFC and LAFC ovarian classes (86.2 ± 7.0a v. 34.6 ± 5.1b and 14.4 ± 3.3c, respectively; P < 0.01). Degenerate primary follicles were higher in the HAFC compared with LAFC ovarian class (16.8 ± 6.5 v. 5.2 ± 2.64; P < 0.05). Normal secondary follicle number was also higher in the HAFC compared to LAFC ovarian classes (25.2 ± 7.67 v. 2.4 ± 0.8; P < 0.05). The number of degenerate secondary follicles differed (P < 0.01) only between the IAFC and the LAFC ovarian classes (0.6 ± 0.4 and 7.2 ± 2.4, respectively), which were similar (P > 0.5) to the HAFC class (3.8 ± 1.0). In experiment 2, grade 1, 2, and 3 oocytes, viable oocytes, and ovarian volume (mm3) were higher (P < 0.001) in HAFC compared with IAFC and LAFC cows (grade 1: 7.9 ± 0.6a, 4.9 ± 0.7b and 3.3 ± 0.7c; grade 2: 4.0 ± 0.4a, 2.8 ± 0.4b and 1.2c; grade 3: 2.1 ± 0.4a, 2.5 ± 0.4a and 1.3 ± 0.5b, respectively; viable oocytes: 16.3 ± 1.1a, 13.1 ± 1.2b, and 8.1 ± 1.3c, respectively; (volumes: 12.6 ± 0.7a, 10.1 ± 0.8b, and 8.1 ± 0.9c, respectively). In conclusion, high AFC is linked to a higher follicular reserve, oocyte quality, and ovarian volume. It is safe to apply AFC in the selection of bovine females without compromising oocyte or pre-antral follicular population qualities.

scholarly journals In vitro ovarian follicle growth: a comprehensive analysis of key protocol variables†

2020 ◽  
Vol 103 (3) ◽  
pp. 455-470
Author(s):  
Leah E Simon ◽  
T Rajendra Kumar ◽  
Francesca E Duncan
Keyword(s):  
Wildlife Conservation ◽  
Culture Media ◽  
Ovarian Follicle ◽  
Three Dimensional ◽  
Ovarian Follicles ◽  
Culture Methods ◽  
Growth And Survival ◽  
Follicle Culture ◽  
Culture Techniques

Abstract Folliculogenesis is a complex process that requires integration of autocrine, paracrine, and endocrine factors together with tightly regulated interactions between granulosa cells and oocytes for the growth and survival of healthy follicles. Culture of ovarian follicles is a powerful approach for investigating folliculogenesis and oogenesis in a tightly controlled environment. This method has not only enabled unprecedented insight into the fundamental biology of follicle development but also has far-reaching translational applications, including in fertility preservation for women whose ovarian follicles may be damaged by disease or its treatment or in wildlife conservation. Two- and three-dimensional follicle culture systems have been developed and are rapidly evolving. It is clear from a review of the literature on isolated follicle culture methods published over the past two decades (1980–2018) that protocols vary with respect to species examined, follicle isolation methods, culture techniques, culture media and nutrient and hormone supplementation, and experimental endpoints. Here we review the heterogeneity among these major variables of follicle culture protocols.

Localization of ovine follistatin and α and βA inhibin mRNA in the sheep ovary during the oestrous cycle

1994 ◽  
Vol 12 (2) ◽  
pp. 181-193 ◽  
Author(s):  
D J Tisdall ◽  
N Hudson ◽  
P Smith ◽  
K P McNatty
Keyword(s):  
Gene Expression ◽  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Indirect Evidence ◽  
Oestrous Cycle ◽  
Corpora Lutea ◽  
Α Subunit ◽  
Ovarian Follicle Development ◽  
Antral Follicles

ABSTRACT The sites of follistatin and α and βA inhibin gene expression were examined by in situ hybridization in sheep ovaries during the early and mid-luteal phases (days 3 and 10) of the oestrous cycle and a prostaglandin F2α (PGF2α)-induced follicular phase. Follistatin mRNA was detected in the granulosa cells of preantral, antral and early atretic follicles at all stages of the oestrous cycle, and in the corpora lutea at the early and mid-luteal stages of the cycle. However, only low levels of expression of follistatin were observed in the presumptive preovulatory follicle at 56 h after treatment with PGF2α. Both α and βA inhibin were shown to be expressed in ovaries at all stages of the oestrous cycle. In situ hybridization localized α subunit mRNA to the granulosa cells of most, but not all, healthy antral follicles, and to no other ovarian cell type. In contrast, expression of the βA subunit was confined to a few medium-to-large healthy antral follicles. In antral follicles expressing βA inhibin, mRNAs for α inhibin and follistatin were always detected, but the converse was not true. Unlike follistatin, no α and βA inhibin expression was seen in preantral follicles, developing corpora lutea, or follicles undergoing atresia. These results show that, in the adult sheep ovary, follistatin gene expression is a constitutive event in all growing follicles from the early preantral stage, and also provide indirect evidence of the involvement of follistatin, but not inhibin or activin, in the early stages of ovarian follicle development in sheep.

scholarly journals Transcriptome Analysis of Ovarian Follicles Reveals Potential Pivotal Genes Associated With Increased and Decreased Rates of Chicken Egg Production

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoxia Chen ◽  
Xue Sun ◽  
Ignatius Musenge Chimbaka ◽  
Ning Qin ◽  
Xiaoxing Xu ◽  
...  
Keyword(s):  
Transcriptome Analysis ◽  
Egg Production ◽  
Ovarian Follicle ◽  
Ovarian Follicles ◽  
Laying Hen ◽  
Egg Laying ◽  
Differentially Expressed ◽  
Molecular Evidence ◽  
Follicle Development ◽  
Ovarian Follicle Development

Egg production is an important economic trait in the commercial poultry industry. Ovarian follicle development plays a pivotal role in regulation of laying hen performance and reproductive physiology. However, the key genes and signaling pathways involved in the various-stages of laying hen follicular development remain poorly understood. In this study, transcriptomes of ovarian follicles at three developmental stages, the large white follicle (LWF), small yellow follicle (SYF), and large yellow follicle (LYF), were comparatively analyzed in hens with high (HR) and low (LR) egg-laying rates by RNA-sequencing. Eighteen cDNA libraries were constructed and a total of 236, 544, and 386 unigenes were significantly differentially expressed in the LWF, SYF, and LYF follicles of HR and LR hens, respectively. Among them, 47 co-transcribed differentially expressed genes (DEGs) in LWF and SYF, 68 co-expressed DEGs in SYF and LYF, and 54 co-expressed DEGs in LWF and LYF were mined. Thirteen co-expressed DEGs were found in LWF, SYF, and LYF follicles. Eighteen candidate genes, including P2RX1, CAB39L, BLK, CSMD3, GPR65, ADRB2, CSMD1, PLPP4, ATF3, PRLL, STMN3, RORB, PIK3R1, PERP1, ACSBG1, MRTO4, CDKN1A, and EDA2R were identified to be potentially related to egg production. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis indicated neuroactive ligand-receptor interaction, cell adhesion molecules, peroxisome proliferator-activated receptor pathway, and cAMP signaling pathway might elicit an important role in formation of egg-laying traits by influencing ovarian follicle development. This study represents the first transcriptome analysis of various-sized follicles between HR and LR hens. These results provide useful molecular evidence for elucidating the genetic mechanism underlying ovarian follicle development associated with egg production in chicken.

Oocyte quality and embryo production in cattle

1998 ◽  
Vol 78 (4) ◽  
pp. 513-516 ◽  
Author(s):  
M.-A. Sirard ◽  
P. Blondin
Keyword(s):  
Growth Phase ◽  
Ovarian Follicle ◽  
Oocyte Quality ◽  
Developmental Competence ◽  
Full Potential ◽  
Plateau Phase ◽  
Follicular Growth ◽  
Transvaginal Aspiration ◽  
New Evidence ◽  
Bovine Oocytes

New evidence indicates that bovine oocytes are not always in synchrony with their surrounding follicles. During rapid follicular growth, the oocytes do not acquire a full developmental competence. The plateau phase at the end of the growth phase resulting in dominance or atresia seems important for oocytes to accumulate the information required to become viable embryos. The ovarian follicle has a behavior similar to a fruit where the seed must await the ripening of the envelope to achieve its full potential. This knowledge can now be applied to harvest oocytes of higher quality through transvaginal aspiration in cows. Key words: Oocyte, embryo, cattle

scholarly journals Samul-tang ameliorates oocyte damage due to cyclophosphamide-induced chronic ovarian dysfunction in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jihyun Kim ◽  
Sooseong You
Keyword(s):  
Molecular Mechanisms ◽  
Ovarian Function ◽  
Bioinformatics Analysis ◽  
Ovarian Tissue ◽  
Ovarian Follicle ◽  
Underlying Mechanism ◽  
Oocyte Quality ◽  
Protective Effects ◽  
Ovarian Dysfunction ◽  
Ovarian Follicle Development

AbstractSamul-tang (SM), a traditional herbal medicine, has been used to treat menstrual irregularities and infertility in women. However, the cellular and molecular mechanisms underlying the effects of SM remain elusive. We investigated the potential protective effect of SM against chronic ovarian dysfunction and used bioinformatics analysis to identify its underlying mechanism in a mouse model of cyclophosphamide (CP)-induced diminished ovarian reserve. Female C57BL/6 mice were intraperitoneally injected with CP three times a week, followed by oral administration of distilled water (CP group) or SM (CP + SM group) for 4 weeks. Four weeks later, the effect of SM was assessed by ovarian tissue histological analysis, steroid hormone measurement, oocyte quality, and mRNA and microRNA microarray analysis in the ovaries. Although SM administration did not prevent CP-induced follicle loss in mice, the quality of oocytes was better in CP + SM mice than in CP mice. Gene expression analysis revealed that the expression of fertilisation- and ovarian follicle development-related genes was altered by CP treatment but normalized after SM administration. Further bioinformatics analysis showed possible interactions between differentially expressed mRNAs and microRNAs. Therefore, we demonstrated the protective effects of SM on ovarian function and oocyte maturation against CP-induced damage via multiple epigenetic mechanisms.

scholarly journals Effect of Date Palm Pollen Supplementation on the Egg Production, Ovarian Follicles Development, Hematological Variables and Hormonal Profile of Laying Hens

Animals ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 69
Author(s):  
Mohamed Saleh ◽  
Dariusz Kokoszyński ◽  
Mohamed Abd-Allah Mousa ◽  
Ahmed Abdel-Kareem Abuoghaba
Keyword(s):  
Egg Production ◽  
Laying Hens ◽  
Ovarian Follicle ◽  
Basal Diet ◽  
Ovarian Follicles ◽  
Control Group ◽  
Egg Mass ◽  
Egg Weight ◽  
Hormonal Profile ◽  
Ovarian Follicle Development

This experiment studied the effect of DPP supplementation in the laying hens’ diet on the ovarian follicle development, hematological variables and hormonal profile of laying hens. Eighty-four, 78-week-old, Lohman LSL hybrids layers were equally divided into four groups (4 groups × 7 replicates × 3 hens); hens in the 1st group were fed a basal diet (control), while those in the 2nd, 3rd and 4th groups, were fed on the same diet and supplemented with 1.25, 2.5 and 5.0 g DPP/kg diet. The results showed that the egg weight, egg mass and laying rate of laying hens treated with DPP levels were significantly increased compared to those of the hens in the control group. Egg weight, egg surface area, albumen quality and percentage of the yolk in treated hens significantly increased compared with controls. The increased DPP levels in laying hens‘ diet significantly (p < 0.05) increased WBC, Hb and TAC, while heterophil/lymphocyte (H/L ratio) significantly decreased. Additionally, the concentrations of FSH and LH and the weights of ovary and oviduct in the treated hens significantly (p < 0.05) increased compared with the control. In conclusion, the DPP supplementation in the hen diet significantly improved egg production, EW, H/L ratio, ovarian follicles, FSH and LH hormones concentrations.

scholarly journals Capillary angiogenesis and degeneration in bovine ovarian antral follicles

Reproduction ◽  
2003 ◽  
pp. 211-223 ◽  
Author(s):  
JY Jiang ◽  
G Macchiarelli ◽  
BK Tsang ◽  
E Sato
Keyword(s):  
Ovarian Follicle ◽  
Apical Part ◽  
Follicular Growth ◽  
Functional Changes ◽  
Antral Follicles ◽  
Theca Interna ◽  
Vascular Plexuses ◽  
Capillary Degeneration ◽  
Capillary Angiogenesis

Angiogenesis and capillary degeneration are both evident during ovarian follicle growth. However, the characteristics and distribution of thecal capillary proliferative and degenerative structures have not been fully defined. Indeed, the role of thecal microvasculature changes in follicular atresia is still a matter of debate. The present study examined the distribution of thecal capillary changes occurring during follicular growth and related the changes to capillary morphology (by scanning electron microscopy, SEM, on bovine ovarian corrosion casts) with the incidence of capillary apoptosis (TdT-mediated dUTP nick end-labelling, TUNEL) and follicular status (as confirmed by follicular fluid steroid concentrations). SEM demonstrated well-perfused vascular plexuses of small to large antral follicles with structural and functional changes to capillaries. Angiogenesis was evident mainly in the apical part of the inner capillary layer of medium follicles and the middle or basal part of the inner capillary layer of dominant follicles that exhibited high oestradiol:progesterone ratios. Degenerative capillaries were observed mainly in the outer vascular layers of small follicles, and in the inner and outer vascular layers of medium antral follicles. Although apoptotic structures were present only in the outer capillaries of the theca interna of morphologically healthy antral follicles, atretic follicles showed apoptotic structures in both the outer and inner thecal capillary layers. These results show that angiogenesis increases during bovine follicular growth and occurs unevenly in different inner theca regions of the follicles. The differential angiogenic and degenerative response of theca interna capillaries may reflect differences in the microenvironment of the follicles, which in turn determine the fate of the follicles (continued growth versus atresia).

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