scholarly journals Aspects of Ovarian Function in a Line of Sheep with a Novel X-Linked Maternally-Imprinted Gene that is Associated with an Increased Ovulation Rate

2021 ◽  
Author(s):  
◽  
Elisabeth Sheinach Feary
Keyword(s):  
Gene Expression ◽  
Pituitary Gland ◽  
Ovarian Function ◽  
Follicular Development ◽  
Cell Types ◽  
Ovulation Rate ◽  
Chromosome 2 ◽  
Ovarian Follicular Development ◽  
Er Alpha ◽  
Large Ovary

<p>Fecundity is a term that refers to the number of offspring produced per female. It combines fertility (i.e. ability to produce offspring) and prolificacy (i.e. number of offspring). Ovulation rate i.e. the number of mature eggs released from the ovaries during one reproductive cycle in sheep, as with other mammals, is controlled by an exchange of hormonal signals between the pituitary gland and the ovary. Genetic mutations affecting ovulation are commonly referred to as the fecundity genes (Fec). The most obvious outcome is the number of offspring produced. There is already evidence of a number of major genes affecting the ovulation rate in sheep, specifically the Booroola, Inverdale, Hanna and more recently the Woodlands gene. The sheep carrying the Woodlands gene arose because the mutation was first recognised on a farm in Woodlands, Southland, New Zealand. Woodlands have a novel, X-linked maternally-imprinted, fecundity trait referred to as FecX2w, where Fec = fecundity, X = X chromosome, 2= 2nd mutation identified on X and W= Woodlands. The studies in this thesis investigated ovarian follicular development in both 4-week old Woodland carrier (W+) and non-carrier (++) lambs and adult ewes and evaluated some aspects of the endocrine interactions between the ovary and pituitary gland. The purpose was to identify potential physiological effects of the FecX2w gene on ovarian function. A confounding issue during these studies was the discovery that a large ovary phenotype (LOP) which was present in many of the W+ but not ++ lambs at 4 weeks of age was in fact a coincidence and not linked to the FecX2w mutation. The key findings from the studies of lambs and/or ewes that were carriers (W+) or non-carriers (++) of the FecX2w gene were: 1. No genotype differences were present either in the numbers of primordial (i.e. Type 1/1a follicles) or developing preantral (i.e. Types 2-4 follicles); 2. Significant genotype differences were present in the numbers of small antral (Type 5) follicles (W+>++; p<0.05); 3. An earlier onset of antral follicular development in W+ vs. ++ ewes with irregularities in morphology between the basement membrane and stroma in the former; 4. No genotype differences in the onset of gene expression during follicular development or in the cell-types expressing GDF9, BMP15, alpha inhibin, beta A inhibin and beta B inhibin, FSHR, ER alpha, or ER beta; 5. No genotype differences in the levels of GDF9 or BMP15 gene expression in oocytes throughout follicular growth; 6. No genotype difference in the diameters that follicles reached in W+ vs. ++ ewes; 7. Some lambs at 4-weeks of age had unusually large ovaries with an exceptional level of antral follicular development that is reminiscent of a polycystic ovarian condition. The underlying cause of this condition is unknown. In conclusion, the physiological characteristics of ovarian follicular development in ewes with the FecX2w gene is different from that in ewes with the Booroola, Inverdale, Hanna or other recently identified mutations.</p>

scholarly journals Aspects of Ovarian Function in a Line of Sheep with a Novel X-Linked Maternally-Imprinted Gene that is Associated with an Increased Ovulation Rate

2021 ◽  
Author(s):  
◽  
Elisabeth Sheinach Feary
Keyword(s):  
Gene Expression ◽  
Pituitary Gland ◽  
Ovarian Function ◽  
Follicular Development ◽  
Cell Types ◽  
Ovulation Rate ◽  
Chromosome 2 ◽  
Ovarian Follicular Development ◽  
Er Alpha ◽  
Large Ovary

<p>Fecundity is a term that refers to the number of offspring produced per female. It combines fertility (i.e. ability to produce offspring) and prolificacy (i.e. number of offspring). Ovulation rate i.e. the number of mature eggs released from the ovaries during one reproductive cycle in sheep, as with other mammals, is controlled by an exchange of hormonal signals between the pituitary gland and the ovary. Genetic mutations affecting ovulation are commonly referred to as the fecundity genes (Fec). The most obvious outcome is the number of offspring produced. There is already evidence of a number of major genes affecting the ovulation rate in sheep, specifically the Booroola, Inverdale, Hanna and more recently the Woodlands gene. The sheep carrying the Woodlands gene arose because the mutation was first recognised on a farm in Woodlands, Southland, New Zealand. Woodlands have a novel, X-linked maternally-imprinted, fecundity trait referred to as FecX2w, where Fec = fecundity, X = X chromosome, 2= 2nd mutation identified on X and W= Woodlands. The studies in this thesis investigated ovarian follicular development in both 4-week old Woodland carrier (W+) and non-carrier (++) lambs and adult ewes and evaluated some aspects of the endocrine interactions between the ovary and pituitary gland. The purpose was to identify potential physiological effects of the FecX2w gene on ovarian function. A confounding issue during these studies was the discovery that a large ovary phenotype (LOP) which was present in many of the W+ but not ++ lambs at 4 weeks of age was in fact a coincidence and not linked to the FecX2w mutation. The key findings from the studies of lambs and/or ewes that were carriers (W+) or non-carriers (++) of the FecX2w gene were: 1. No genotype differences were present either in the numbers of primordial (i.e. Type 1/1a follicles) or developing preantral (i.e. Types 2-4 follicles); 2. Significant genotype differences were present in the numbers of small antral (Type 5) follicles (W+>++; p<0.05); 3. An earlier onset of antral follicular development in W+ vs. ++ ewes with irregularities in morphology between the basement membrane and stroma in the former; 4. No genotype differences in the onset of gene expression during follicular development or in the cell-types expressing GDF9, BMP15, alpha inhibin, beta A inhibin and beta B inhibin, FSHR, ER alpha, or ER beta; 5. No genotype differences in the levels of GDF9 or BMP15 gene expression in oocytes throughout follicular growth; 6. No genotype difference in the diameters that follicles reached in W+ vs. ++ ewes; 7. Some lambs at 4-weeks of age had unusually large ovaries with an exceptional level of antral follicular development that is reminiscent of a polycystic ovarian condition. The underlying cause of this condition is unknown. In conclusion, the physiological characteristics of ovarian follicular development in ewes with the FecX2w gene is different from that in ewes with the Booroola, Inverdale, Hanna or other recently identified mutations.</p>

Effect of active immunization of heifers against inhibin on plasma FSH concentrations, ovarian follicular development and ovulation rate

1992 ◽  
Vol 134 (1) ◽  
pp. 11-18 ◽  
Author(s):  
R. G. Glencross ◽  
E. C. L. Bleach ◽  
B. J. McLeod ◽  
A. J. Beard ◽  
P. G. Knight
Keyword(s):  
Synthetic Peptide ◽  
Ovarian Function ◽  
Statistical Significance ◽  
Follicular Development ◽  
Ovarian Response ◽  
Active Immunization ◽  
Ovulation Rate ◽  
Corpora Lutea ◽  
Α Subunit ◽  
Ovarian Follicular Development

ABSTRACT To study the effects of immunoneutralization of endogenous inhibin on gonadotrophin secretion and ovarian function, prepubertal heifers (n = 6) were actively immunized against a synthetic peptide replica of the N-terminal sequence of bovine inhibin α subunit bIα(1–29)Tyr30) coupled to ovalbumin. In contrast to ovalbumin-immunized controls (n=6), bIα(1–29)Tyr30-immunized heifers had detectable inhibin antibody titres (% binding to 125I-labelled bovine inhibin at 1:2000 dilution of plasma) of 17 ± 3% (s.e.m.) at puberty, rising to 31 ± 5% by the end of the study period 7 months later. Neither age (immunized: 295 ± 8 days; controls: 300 ± 5 days) nor body weight (immunized: 254 ± 13 kg; controls 251 ± 9 kg) at onset of puberty differed between groups. Although the difference did not reach statistical significance, mean plasma FSH concentrations recorded in inhibin-immunized heifers remained 35–40% higher than in controls throughout the 12-week period leading up to puberty (P = 0·14) and during nine successive oestrous cycles studied after puberty (P=0·10). Plasma LH concentrations did not differ between groups at any time during the study. Inhibin immunization had no effect on oestrous cycle length (immunized: 19·8±0·5 days; controls: 19·9±0·5 days). However, in comparison with controls, inhibinimmunized heifers had more medium sized (≥0·5 to <1 cm diameter) follicles during both the preovulatory (95%, P<0·001) and post-ovulatory (110%, P < 0·05 waves of follicular growth and more large (>1 cm diameter) follicles during the preovulatory wave (49%, P<0·05). In addition, the number of corpora lutea observed during the post-ovulatory phase of each cycle was significantly greater in the inhibin-immunized group (43%, P<0·01), as was the recorded incidence of cycles with multiple ovulations (19/56 in the inhibin-immunized group compared with 0/54 in controls; P<0·001). All six inhibinimmunized heifers had at least one cycle with multiple ovulation whereas none of the control heifers did so. These results support the conclusion that immunoneutralization of endogenous inhibin using a synthetic peptide-based vaccine can enhance ovarian follicular development and ovulation rate in heifers. Whether this ovarian response is dependent upon the expected increase in secretion of FSH remains to be established. Journal of Endocrinology (1992) 134, 11–18

scholarly journals Effects of active immunization against growth differentiation factor 9 and/or bone morphogenetic protein 15 on ovarian function in cattle

Reproduction ◽  
2009 ◽  
Vol 138 (1) ◽  
pp. 107-114 ◽  
Author(s):  
Jennifer L Juengel ◽  
Norma L Hudson ◽  
Martin Berg ◽  
Keith Hamel ◽  
Peter Smith ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Ovarian Function ◽  
Follicular Development ◽  
Active Immunization ◽  
Ovulation Rate ◽  
Differentiation Factor ◽  
Morphogenetic Protein ◽  
Growth Differentiation Factor 9 ◽  
Bone Morphogenetic Protein 15 ◽  
Ovarian Follicular Development

Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are essential for ovarian follicular growth in sheep, whereas only GDF9 is essential in mice suggesting that the roles of these oocyte-derived growth factors differ among species. At present, however, there is only limited information on the action of BMP15 and GDF9 in other species. Thus, the aim of this experiment was to determine the effect of neutralizing GDF9 and/or BMP15in vivoon ovarian follicular development and ovulation rate in cattle through active immunization using the mature regions of the proteins or peptides from the N-terminal area of mature regions. Immunization with the BMP15 peptide, with or without GDF9 peptide, significantly altered (increased or decreased) ovulation rate. In some animals, there were no functional corpora lutea (CL), whereas in others up to four CL were observed. From morphometric examination of the ovaries, immunization with GDF9 and/or BMP15 reduced the level of ovarian follicular development as assessed by a reduced proportion of the ovarian section occupied by antral follicles. In addition, immunization against GDF9 and/or BMP15 peptides reduced follicular size to <25% of that in the controls. In conclusion, immunization against GDF9 and BMP15, alone or together, altered follicular development and ovulation rate in cattle. Thus, as has been observed in sheep, both GDF9 and BMP15 appear to be key regulators of normal follicular development and ovulation rate in cattle.

scholarly journals Pcsk6 mutant mice exhibit progressive loss of ovarian function, altered gene expression, and formation of ovarian pathology

Reproduction ◽  
2011 ◽  
Vol 141 (3) ◽  
pp. 343-355 ◽  
Author(s):  
Michelle L Mujoomdar ◽  
Laura M Hogan ◽  
Albert F Parlow ◽  
Mark W Nachtigal
Keyword(s):  
Gene Expression ◽  
Ovarian Function ◽  
Elevated Serum ◽  
Cell Types ◽  
Reproductive Capacity ◽  
Wide Range ◽  
Altered Gene ◽  
Ovarian Pathology ◽  
Targeted Gene Expression ◽  
Benign Ovarian Tumors

Bioactivation of precursor proteins by members of the proprotein convertase (PC) family is essential for normal reproduction. ThePcsk6gene is a member of the PC family that is expressed in numerous ovarian cell types including granulosa cells and oocytes. We hypothesized that loss of PCSK6 would produce adverse effects in the mouse ovary. Mice incapable of expressing PCSK6 (Pcsk6tm1Rob) were obtained, and reproductive parameters (serum hormones, whelping interval, estrus cyclicity, and fertility) were compared toPcsk6+/+mice. WhilePcsk6tm1Robfemale mice are fertile, they manifest reduced reproductive capacity at an accelerated rate relative toPcsk6+/+mice. Reproductive senescence is typically reached by 9 months of age and is correlated with loss of estrus cyclicity, elevated serum FSH levels, and gross alterations in ovarian morphology. A wide range of ovarian morphologies were identified encompassing mild, such as an apparent reduction in follicle number, to moderate – ovarian atrophy with a complete absence of follicles – to severe, manifesting as normal ovarian structures replaced by benign ovarian tumors, including tubulostromal adenomas. Targeted gene expression profiling highlighted changes in RNA expression of molecules involved in processes such as steroidogenesis, gonadotropin signaling, transcriptional regulation, autocrine/paracrine signaling, cholesterol handling, and proprotein bioactivation. These results show that PCSK6 activity plays a role in maintaining normal cellular and tissue homeostasis in the ovary.

Ovarian follicular development during the follicular phase of oestrous cycle in manchega ewes with different ovulation rate

1996 ◽  
Vol 45 (1) ◽  
pp. 299 ◽  
Author(s):  
A.Gómez Brunet ◽  
A.López Sebastián ◽  
A.González de Bulnes ◽  
J.Santiago Moreno ◽  
M.García López
Keyword(s):  
Follicular Development ◽  
Follicular Phase ◽  
Oestrous Cycle ◽  
Ovulation Rate ◽  
Ovarian Follicular Development

Factors affecting folliculogenesis in ruminants

1999 ◽  
Vol 68 (2) ◽  
pp. 257-284 ◽  
Author(s):  
R. Webb ◽  
R. G. Gosden ◽  
E. E. Telfer ◽  
R. M. Moor
Keyword(s):  
New Technologies ◽  
Ovarian Function ◽  
Major Gene ◽  
Follicular Development ◽  
Oocyte Quality ◽  
Ovulation Rate ◽  
Follicular Growth ◽  
Stages Of Development ◽  
Hormone Production ◽  
Factors Affecting

AbstractThis review addresses the reasons for the lack of progress in the control of superovulation and highlights the importance of understanding the mechanisms underlying follicular development. The present inability to provide large numbers of viable embryos from selected females still restricts genetic improvement, whilst variability in ovarian response to hormones limit the present capacity for increasing reproductive efficiency.Females are born with a large store of eggs which rapidly declines as puberty approaches. If these oocytes are normal then there is scope for increasing the reproductive potential of selected females. Oocytes must reach a certain size before they can complete all stages of development and the final changes that occur late in follicular development. It is likely that oocytes that do not produce specific factors at precise stages of development will not be viable. Hence, it is important to characterize oocyte secreted factors since there are potential indicators of oocyte quality.The mechanisms that determine ovulation rate have still not been fully elucidated. Indeed follicular atresia, the process whereby follicles regress, is still not known. A better understanding of these processes should prove pivotal for the synchronization of follicular growth, for more precise oestrous synchronization and improved superovulatory response.Nutrition can influence a whole range of reproductive parameters however, the pathways through which nutrition acts have not been fully elucidated. Metabolic hormones, particularly insulin and IGFs, appear to interact with gonadotrophins at the level of the gonads. Certainly gonadotropins provide the primary drive for the growth of follicles in the later stages of development and both insulin and IGF-1, possibly IGF-2, synergize with gonadotrophins to stimulate cell proliferation and hormone production. More research is required to determine the effects of other growth factors and their interaction with gonadotropins.There is evidence, particularly from studies with rodents, that steroids can also modulate follicular growth and development, although information is very limited for ruminants. There may be a rôle for oestrogens in synchronizing follicular waves, to aid in oestrous synchronization regimes and for removing the dominant follicle to achieve improved superovulatory responses. However more information is required to determine whether these are feasible approaches.Heritability for litter size is higher in sheep than in cattle. Exogenous gonadotropins are a commercially ineffective means of inducing twinning in sheep and cattle. Although there are differences in circulating gonadotropin concentrations, the mechanism(s) responsible for the high ovulation appear to reside essentially within the ovaries. The locus of the Booroola gene, a major gene for ovulation rate, has been established but not specifically identified. However sheep possessing major genes do provide extremely valuable models for investigating the mechanisms controlling ovulation rate, including a direct contrast to mono-ovulatory species such as cattle.In conclusion, the relationship between oocyte quality, in both healthy follicles and those follicles destined for atresia, must be resolved before the future potential for increasing embryo yield can be predicted. In addition, a greater understanding of the factors affecting folliculogenesis in ruminants should ensure that the full benefits ensuing from the precise control of ovarian function are achieved. The improved use of artificial insemination and embryo transfer that would ensue from a greater understanding of the processes of folliculo genesis, coupled with the new technologies of genome and linkage mapping, should ensure a more rapid rate of genetic gain.

scholarly journals Impact of maternal nutrition during pregnancy on pituitary gonadotrophin gene expression and ovarian development in growth-restricted and normally grown late gestation sheep fetuses

Reproduction ◽  
2002 ◽  
pp. 769-777 ◽  
Author(s):  
P Da Silva ◽  
RP Aitken ◽  
SM Rhind ◽  
PA Racey ◽  
JM Wallace
Keyword(s):  
Gene Expression ◽  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Nutrient Intake ◽  
Ovarian Development ◽  
Maternal Nutrition ◽  
Follicular Development ◽  
Late Gestation ◽  
Complete Diet ◽  
High Nutrient

The influence of maternal nutrition during pregnancy on anterior pituitary gonadotrophin gene expression and ovarian development in sheep fetuses during late gestation was investigated. Embryos recovered from superovulated adult ewes that had been inseminated by a single sire were transferred, singly, into the uteri of adolescent recipients. After embryo transfer, adolescent ewes were offered a high or moderate amount of a complete diet. Pregnancies were terminated at day 131 +/- 0.6 of gestation and the fetal brain, anterior pituitary gland and gonads were collected. Gonadotrophin gene expression (LHbeta and FSHbeta subunits) in the fetal pituitary gland was examined using in situ hybridization. Ovarian follicular development was quantified in haematoxylin- and eosin-stained ovarian sections embedded in paraffin wax. Six dams that were offered a high nutrient intake carried normal-sized fetuses (weight within +/- 2 SD of mean weight for control fetuses from dams fed a moderate level of complete diet) and 13 dams carried growth-restricted fetuses (weight +/- 2 SD of mean weight for control fetuses from dams fed a moderate level of complete diet). Mean placental masses in these groups were 354 +/- 24.5 and 230 +/- 21.1 g, respectively, compared with 442 +/- 54.3 g in the dams that were offered a moderate nutrient intake (n = 6). Growth-restricted fetuses from dams offered a high nutrient intake showed higher pituitary LHbeta mRNA expression (P < 0.05) than normal-sized fetuses from dams offered a moderate nutrient intake (252 +/- 21.6 and 172 +/- 23.6 nCi g(-1), respectively). FSHbeta mRNA expression was not influenced by growth status. Fewer follicles (primarily in the resting pool) were observed in the ovaries of both growth-restricted (P < 0.002) and normal-sized fetuses from dams offered a high nutrient intake (P < 0.01) compared with normal-sized fetuses from dams offered a moderate nutrient intake. Irrespective of nutritional treatment, the total number of follicles was positively associated with placental mass (P < 0.01). Thus, a high maternal nutrient intake during adolescent pregnancy had a negative influence on ovarian follicular development in fetuses as determined during late gestation.

scholarly journals In Utero and Lactational Exposure to Flame Retardants Disrupts Rat Ovarian Follicular Development and Advances Puberty

2020 ◽  
Vol 175 (2) ◽  
pp. 197-209 ◽  
Author(s):  
Adélaïde Allais ◽  
Océane Albert ◽  
Pavine L C Lefèvre ◽  
Michael G Wade ◽  
Barbara F Hales ◽  
...  
Keyword(s):  
Gene Expression ◽  
Polybrominated Diphenyl Ethers ◽  
Flame Retardants ◽  
Ovarian Function ◽  
Expression Patterns ◽  
Follicular Development ◽  
In Utero ◽  
Consumer Products ◽  
Sprague Dawley ◽  
Lactational Exposure

Abstract Brominated flame retardants (BFRs), including polybrominated diphenyl ethers and hexabromocyclododecane, leach out from consumer products into the environment. Exposure to BFRs has been associated with effects on endocrine homeostasis. To test the hypothesis that in utero and lactational exposure to BFRs may affect the reproductive system of female offspring, adult female Sprague Dawley rats were fed diets formulated to deliver nominal doses (0, 0.06, 20, or 60 mg/kg/day) of a BFR dietary mixture mimicking the relative congener levels in house dust from prior to mating until weaning. Vaginal opening and the day of first estrus occurred at a significantly earlier age among offspring from the 20 mg/kg/day BFR group, indicating that the onset of puberty was advanced. Histological analysis of ovaries from postnatal day 46 offspring revealed an increase in the incidence of abnormal follicles. A toxicogenomic analysis of ovarian gene expression identified upstream regulators, including HIF1A, CREB1, EGF, the β-estradiol, and PPARA pathways, predicted to be downregulated in the 20 or 60 mg/kg/day group and to contribute to the gene expression patterns observed. Thus, perinatal exposure to BFRs dysregulated ovarian folliculogenesis and signaling pathways that are fundamental for ovarian function in the adult.

scholarly journals The conflict between hierarchical ovarian follicular development and superovulation treatment

Reproduction ◽  
2010 ◽  
Vol 140 (2) ◽  
pp. 287-294 ◽  
Author(s):  
Kenneth P McNatty ◽  
Derek A Heath ◽  
Norma L Hudson ◽  
Karen L Reader ◽  
Laurel Quirke ◽  
...  
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Follicular Development ◽  
Follicular Phase ◽  
Ovulation Rate ◽  
Cell Populations ◽  
Antral Follicles ◽  
Functional States ◽  
Ovarian Follicular Development

In mammals with a low ovulation rate phenotype, ovarian follicular development is thought to be hierarchical with few, if any, antral follicles at similar stages of development. The hypothesis being tested herein was that if most follicles are in a functionally different state, then the application of exogenous hormones to increase ovulation rate will not overcome the hierarchical nature of follicular development. Using sheep as the experimental model, the functional states of all non-atretic antral follicles ≥2 mm diameter were assessed in individual ewes (N=10/group) during anoestrus with or without pregnant mare's serum gonadotrophin (PMSG) treatment, or after a standard superovulation regimen, or during the follicular phase of the oestrous cycle. The functional states of these follicles were assessed by measuring the FSH- or human chorionic gonadotrophin (hCG)-induced cAMP responses of granulosa cellsin vitro. There were significant overall effects across the treatment groups on the responses of granulosa cells to either FSH or LH (bothP<0.001). It was concluded that for anoestrous ewes with or without PMSG treatment, and ewes during the follicular phase, granulosa cell populations of many follicles (≥2 mm diameter) did not share a similar cAMP response to FSH (∼50% of follicles) or hCG (>90% of follicles) either on a per cell or total cell basis. After superovulation, ≤30 and 10% respectively of the granulosa cell populations shared similar responses to FSH and LH with regard to follicular diameter and cAMP output. Thus, exogenous hormone treatments used routinely for increasing oocyte yield do not effectively override the hierarchical pattern of ovarian follicular development during the follicular phase.

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