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Mammalian females are born with a finite number of follicles in their ovaries that is referred to as the ovarian reserve. There is a large amount of variation between females in the number of antral follicles that they are born with, but this number is positively correlated to size of the ovarian reserve, has a strong repeatability within a female, and a moderate heritability. Although the heritability is moderate, numerous external factors including health, nutrition, ambient temperature, and litter size influence the size and function of the ovarian reserve throughout life. Depletion of the ovarian reserve contributes to reproductive senescence, and genetic and epigenetic factors can lead to a more rapid decline in follicle numbers in some females than others. The relationship of the size of the ovarian reserve to development of the reproductive tract and fertility is generally positive, although some studies report antagonistic associations of these traits. It seems likely that management decisions and environmental factors that result in epigenetic modifications to the genome throughout life may cause variability in the function of ovarian genes that influence fecundity and fertility, leading to differences in reproductive longevity among females born with ovarian reserves of similar size. This review summarizes our current understanding of factors influencing size of the ovarian reserve in cattle, sheep, and pigs and the relationship of the ovarian reserve to reproductive tract development and fertility. It provides strategies to apply this knowledge to improve diagnostics for better assessment of fertility and reproductive longevity in female livestock., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Published by Elsevier B.V.)

As prenatal transportation stress altered behavior and adrenal glucocorticoid secretion of calves, we hypothesized that prenatal transportation stress would decrease ovarian reserve size and negatively impact female offspring fertility. The impact of prenatal transportation stress on ovarian follicle numbers in female offspring for three generations was studied. Brahman cows were transported for 2 h on day 60 ± 5, 80 ± 5, 100 ± 5, 120 ± 5, and 140 ± 5 of gestation. Ovaries were collected from offspring of transported or non-transported dams at multiple ages. Primordial, primary, secondary, and antral follicles were histologically analyzed. Antral follicle numbers were determined by ultrasound in a subset of offspring. Numbers of primordial, primary, secondary, and antral follicles were analyzed using the MIXED procedure, while the CORR procedure of SAS was used to determine the correlation between follicles observed by ultrasonography and histology. There were no differences (P > 0.05) in the number of primordial, primary, secondary, antral, or total follicles observed histologically due to treatment. Younger females had significantly greater numbers of follicles than older females (P < 0.0001). Antral follicles tended to be correlated with total histological ovarian follicles (P = 0.10). There was no difference in the number of antral follicles observed at ultrasound due to treatment (P = 0.3147), or generation (P = 0.6005) when controlling for age at observation. These results show that short-term transportation stress during early- to mid-gestation did not impact fertility as measured by ovarian follicle numbers in female Brahman offspring for three generations., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Bos indicus females have more surface antral follicles than Bos taurus females; however, histological studies demonstrated no difference in total number of primordial follicles between these two biological types of cattle. Primordial follicle density in the ovary was less in Nelore ovaries compared to Angus ovaries, but no studies have examined the primordial follicle density in Bos indicus cross-bred females. It, therefore, was hypothesized that primordial follicle density in the ovary would decrease as percentage Bos indicus increased. Ovaries were collected from cross-bred Angus (n = 32, no Bos indicus influence), Brangus (n = 15), or Brahman (n = 9) cows and prepared for histological evaluation. There was no difference in total number of primordial follicles per ovary between breeds (P > 0.10). When numbers of primordial follicles were expressed on a per gram of ovarian tissue basis, there were fewer primordial follicles per gram of ovarian tissue in Brangus and Brahman cows than in Angus cows (P < 0.05). Brangus cows did not differ from Brahman cows in primordial follicle density (P > 0.10). Differences in primordial follicle density could indicate differences in capacity of ovarian stroma to produce factors necessary for oogonial proliferation and primordial follicle formation among breeds. Identifying these factors could improve the aprroach for culturing pre-antral follicles of cattle. Furthermore, these results explain why ultrasonographic antral follicle counts may need to be adjusted to a greater threshold to predict size of the ovarian reserve and determine ovarian reserve related reproductive traits in Bos indicus females., (Published by Elsevier B.V.)

The number of antral follicles detectable by ultrasonography in heifers is influenced by age of the dam, because daughters of primiparous cows have fewer antral follicles than daughters of mature cows. We, therefore, hypothesized that heifers with primiparous dams would have fewer primordial follicles in their ovaries than heifers born to mature (4+ y) cows. Angus heifers (n = 464) were submitted for ultrasonographic evaluation of antral follicle number at 325, 355, and 385 d of age. Ovaries were collected from a random subset of heifers (n = 79) and processed for histological evaluation to determine number of primordial follicles. A greater percentage of heifers with primiparous dams had a corpus luteum at first ultrasonographic examination; however, a greater percentage of heifers with multiparous dams had ovulated by the start of breeding (P <  0.01). Heifers with primiparous dams had fewer antral follicles detectable by ultrasonography (P <  0.01). Heifers with primparous dams had fewer surface antral follicles on their ovaries (P <  0.01), and the number of primordial follicles per histological section was less for heifers with primiparous dams (P =  0.02). These data indicate that the lesser number of antral follicles detectable by ultrasonography in heifers with primparous dams is due to less ovarian follicle reserves. Selecting replacement heifers from mature dams may result in daughters with greater fertility and reproductive longevity; however, further research is necessary to determine if interactions between size of the ovarian follicle reserve and age at puberty influence fertility and reproductive longevity in replacement heifers., (Published by Elsevier B.V.)

Management strategies utilized during pre-breeding development of replacement heifers can impact fertility and the ovarian reserve. Angus-Hereford crossbred heifers (n = 233) were utilized over a 3-yr period to determine the effects of administration of a growth promoting implant at either branding or weaning on growth, reproduction, and ovarian development. Heifer calves were randomly assigned to one of three treatments: 1) nonimplanted controls (CON; n = 79), 2) implanted at approximately 2 mo of age (average calf age = 58 d) with Synovex-C (BIMP, n = 82), or 3) implanted at approximately 7 mo of age (average calf age = 210 d) with Synovex-C (WIMP; n = 72). In years 2 and 3, a subset of heifers (year 2 n = 16; year 3 n = 14) were unilaterally ovariectomized. Heifers implanted at 2 mo of age were heavier at weaning, yearling (mid-February; average calf age = 332 d), and at the beginning of the breeding season (P < 0.01) compared to CON and WIMP heifers. Average daily gain (ADG) was similar among treatments from weaning to yearling and weaning to the start of the breeding season (P ≥ 0.61); however, WIMP heifers had increased (P = 0.05) ADG from yearling to the start of the breeding season compared to BIMP heifers. Antral follicle count and reproductive tract scores were not influenced by implant treatment (P ≥ 0.18). Response to synchronization of estrus was increased (P = 0.02) in WIMP compared to CON heifers, with BIMP heifers similar to all other treatments. First service conception rates tended to be increased (P = 0.09) in CON heifers compared to WIMP heifers, with BIMP heifers similar to CON and WIMP. Final pregnancy rates were similar (P = 0.54) among treatments. A treatment × yr interaction was detected (P = 0.01) for the number of primordial follicles/section with increased primordial follicles in WIMP heifers in year 3 compared to BIMP and WIMP heifers in year 2 and CON heifers in year 3, as well as in BIMP compared to WIMP heifers in year 2. Utilization of growth promoting implants did not negatively impact postweaning reproductive development or compromise pregnancy rates in beef heifers. Based on these results, administration of a growth promoting Synovex-C implant at 2 mo of age may allow for increased body weight at weaning, without hindering reproductive performance. [ABSTRACT FROM AUTHOR]

This review resulted from an international workshop and presents a consensus view of critical advances over the past decade in our understanding of follicle function in ruminants. The major concepts covered include: (1) the value of major genes; (2) the dynamics of fetal ovarian development and its sensitivity to nutritional and environmental influences; (3) the concept of an ovarian follicle reserve, aligned with the rise of anti-Müllerian hormone as a controller of ovarian processes; (4) renewed recognition of the diverse and important roles of theca cells; (5) the importance of follicular fluid as a microenvironment that determines oocyte quality; (6) the 'adipokinome' as a key concept linking metabolic inputs with follicle development; and (7) the contribution of follicle development to the success of conception. These concepts are important because, in sheep and cattle, ovulation rate is tightly regulated and, as the primary determinant of litter size, it is a major component of reproductive efficiency and therefore productivity. Nowadays, reproductive efficiency is also a target for improving the 'methane efficiency' of livestock enterprises, increasing the need to understand the processes of ovarian development and folliculogenesis, while avoiding detrimental trade-offs as greater performance is sought. [ABSTRACT FROM AUTHOR]

Ovarian ultrasonography and measurement of circulating concentrations of anti-Müllerian hormone (AMH) have been used to estimate follicle number and predict fertility in mammalian females, but no study has evaluated follicle number and circulating concentrations of AMH in ewes known to differ in fertility. We tested the hypothesis that ewes that had failed to lamb (BARREN) in four consecutive annual breeding seasons of 21–35 d have fewer follicles and diminished circulating concentrations of AMH compared to closely matched ewes that consistently produced lambs (FERTILE) under the same breeding protocols. Once identified, BARREN ewes (n = 19) were paired by breed and sire to a FERTILE control ewe (n = 19) and reproductive tracts were recovered at necropsy. Visible antral follicles in both ovaries were counted and a representative cross section of one ovary was embedded for histological evaluation of pre-antral follicle numbers. Paired t-tests indicated that BARREN ewes had fewer antral follicles, fewer primordial follicles, and decreased circulating concentrations of AMH compared to FERTILE ewes (P ≤ 0.01), but there were ewes in each fertility classification that had ovarian phenotypes like the opposite fertility classification. The best technologies we have currently for estimating follicle numbers are ultrasonography and measurement of circulating concentrations of AMH, but no single technique is perfect for predicting fertility. A better understanding of the under-lying biological mechanisms linking AMH, folliculogenesis, and fertility is required to improve the use of measurements of follicle number for predicting fertility in livestock. • Most infertile ewes had fewer follicles in their ovaries than fertile ewes. • Circulating anti-Müllerian hormone was decreased in most infertile ewes. • Predictors of follicle number could identify a large portion of the infertile ewes. [ABSTRACT FROM AUTHOR]

Mammalian females are born with a finite supply of follicles within their ovaries that may be related to fertility and reproductive longevity. The number of microscopic follicles in the ovarian cortex is positively correlated to the number of antral follicles. In cattle, the number of antral follicles can be determined by ultrasonographic examination of the ovaries, is repeatable within a female, and has a moderate heritability. Studies in rodents suggest that nutritional status early in life can alter structure and function of the ovarian reserve, resulting in changes in follicle numbers, estrous cycle parameters, and reproductive longevity. This raises questions about how early life events might influence the ovarian reserve and reproductive performance in bovine females. A central hypothesis of our research is that the number of follicles that a heifer has when entering her first breeding season is influenced by external factors such as maternal nutrition during pregnancy, maternal stress during pregnancy, peri-pubertal nutrition, and health events. Understanding how these factors influence the structure and function of the ovarian reserve in replacement heifers may allow us to translate this knowledge into management practices that developmentally program the bovine ovary prior to the first breeding season to improve reproductive performance in the cow herd. Accomplishing this is made difficult because our understanding of the mechanisms controlling pre-antral follicle development in cattle is limited and growth of pre-antral follicles is occurring at the microscopic level within the ovarian cortex where it is difficult to monitor changes in real time. There has been some success, but variation in response across studies indicates that further research to understand the causes of this variation is required before we will be able to apply developmental programming in beef production systems to improve ovarian function in replacement heifers. USDA is an equal opportunity provider and employer. [ABSTRACT FROM AUTHOR]

The relationship of ovarian reserve parameters to fertility in mammalian females continues to be debated. We demonstrated improved uterine function, creating an environment that is more supportive of early embryonic development in beef heifers with increased numbers of follicles. In the present study we hypothesized that timing of luteolysis differs between heifers with increased compared to heifers with diminished numbers of follicles. Angus heifers (n = 20/group) were classified as low (14.7 ± 1.1) or high (32 ± 1.1) antral follicle number based on ovarian ultrasonography, and artificially inseminated (d0) following a Select Synch protocol. At d16 after insemination, heifers were slaughtered, and reproductive tracts collected. Tracts were flushed with 20 mL of physiological saline to determine pregnancy status by presence of a conceptus and endometrial samples from the horn ipsilateral to the CL were frozen for determination of transcript abundance. Real-time RT-PCR was performed to determine relative transcript abundance of oxytocin receptor (OXTR) and interferon-stimulated gene-15 (ISG15) with glyceraldehyde-3-phospate dehydrogenase as the endogenous reference gene. Transcript abundance was analyzed using the MIXED procedure of SAS with follicle group, pregnancy status and the interaction as fixed effects. Transcript abundance of ISG15 was greater in pregnant endometrium than non-pregnant endometrium (2.75 ± 0.25 vs 0.16 ± 0.22-fold; P < 0.0001) with no influence of follicle group or the interaction. The interaction of follicle group and pregnancy status influenced OXTR transcript abundance (P = 0.06). Luteolytic mechanisms were activated in non-pregnant heifers with diminished numbers of follicles (1.46 ± 0.25-fold) and were not activated in pregnant heifers (0.06 ± 0.22-fold) or heifers with increased numbers of follicles that were not pregnant (0.32 ± 0.30-fold). These data indicate a wider window of recognition of pregnancy in beef heifers with increased numbers of ovarian follicles. USDA is an equal opportunity provider and employer. [ABSTRACT FROM AUTHOR]

Increased numbers of antral follicles are associated with greater fertility and a uterine environment that is more supportive of early embryonic development in beef heifers. Glucose is a primary energy source for embryos and glucose concentrations are elevated in uterine luminal fluid (ULF) of pregnant heifers. We hypothesized that ULF glucose concentrations and endometrial transcript abundance for glucose transporters at d16 after insemination would be greater in heifers with increased numbers of antral follicles. Heifers classified with either increased (32 ± 1.1) or diminished (14.7 ± 1.1) antral follicle counts were selected and artificially inseminated following the Select Synch protocol (d0). At d16 after insemination, heifers were sent to the abattoir and reproductive tracts were collected to retrieve conceptuses to determine pregnancy. Uterine luminal fluid was collected, the endometrium was biopsied, total RNA was extracted and glucose transporter transcript abundance was determined. Data were analyzed using the MIXED procedure of SAS with antral follicle group, pregnancy status, and the interaction as fixed effects. Glucose concentrations in ULF were greater (P < 0.05) in heifers with increased antral follicle numbers compared to heifers with diminished numbers (122.65 ± 11.91 vs 84.12 ± 12.42 mg/dL). Glucose ULF concentrations were increased (P < 0.05) in pregnant vs. nonpregnant heifers (124.84 ± 12.81 vs 81.93 ± 11.50 mg/dL). Endometrial glucose transporter 1 (GLUT1) transcript abundance was increased in pregnant heifers (P < 0.01) but was not different due to antral follicle number or the interaction. Therefore, differences in glucose concentrations associated with antral follicle number may be due to differences in GLUT1 transcription before d16 or due to differences in protein abundance or functionality. Taken together, heifers with increased number of antral follicles may have increased energy availability in the uterus for trophoblast proliferation and function. USDA is an equal opportunity provider and employer. [ABSTRACT FROM AUTHOR]

Calves from transported dams had greater concentrations of plasma cortisol when restrained and cleared plasma cortisol at a slower rate than calves from nontransported dams. Considering this hypothalamicpituitary-adrenal axis effect, investigation of other parameters influencing reproduction is warranted in offspring exposed to prenatal transportation stress. The purpose was to determine impact of prenatal transportation stress on offspring ovarian follicle count. Brahman cows were transported for 2 h on d 60, 80, 120, and 140 (± 5 d) of gestation. Offspring from transported (Stressed, n = 19) or non-transported (Control, n = 15) dams were slaughtered at 5 yr (Replication 1, n = 14) or ovariectomized at 8 yr (Replication 2, n = 20). A cross-section of ovary was collected, serially sectioned, and stained. Numbers of total, primordial, primary, secondary, and antral follicles were determined per section. Total ovarian follicle count for each stage was calculated using ovary dimensions. The MIXED procedure of SAS was used to analyze ovarian follicle count with treatment, replicate, and the interaction as fixed effects. Total ovarian follicle count decreased with age (P < 0.01; R1 = 383,663, R2 = 154,560); however, there was no difference in total ovarian follicle count between offspring due to treatment (P = 0.17; S = 221,813, C = 316,409). Similarly, there was no difference in primordial (P = 0.22; S = 127,300, C = 188,304), primary (P = 0.28; S = 58,610, C = 77,237), or antral (P = 0.48; S = 23,202, C = 28,695) follicle count between offspring due to treatment. Fewer secondary follicles were observed in Stressed offspring compared to Control offspring (P = 0.03). These results suggest that the ovarian follicular reserve, AFC, and potential fertility of cows may not be impacted by exposure to prenatal transportation stress. USDA is an equal opportunity provider and employer. [ABSTRACT FROM AUTHOR]

While sequence variation can be informative to associate regions of the genome with specific traits and improve genetic selection, the epigenome may provide a more powerful tool to manage cattle. Identifying practices that are producer friendly and effectively control epigenetic function within animals is crucial to translating developmental programming to a production setting. Initial studies of developmental programming investigated how environmental or nutritional stresses during fetal and peri-natal development impacted performance of animals later in life. These studies demonstrated changes in methylation, alterations in transcript abundance, and negative impacts on physiology, but they also suggested that we may be able to beneficially impact the epigenome and developmentally program animals to excel in their niche in the production system. Maternal nutritional status during the third trimester influenced date of conception of female progeny in several studies but failed to do so in other studies. Transcriptomic analyses provided evidence that nutritional treatments alter mRNA abundance in brain, liver, muscle, and ovary, but does not conclusively demonstrate that this is due to functional changes in the epigenome. If developmental programming is to be applied in production systems, responses must be consistent and beneficial. Reducing nutrient intake in heifers during peri-pubertal development increased number of primordial follicles in the ovaries and reproductive longevity. While nutritional programming of the ovarian reserve in peri-pubertal heifers appears to occur consistently across locations and studies, it does not ensure that subsequent environmental stressors will not induce changes in the ovarian reserve that will negate beneficial effects. These studies demonstrate that it is possible to developmentally program the epigenome in cattle in ways that will improve production traits; however, there remains a need for studies to improve the consistency of response and to determine best practices that fit into production systems. USDA is an equal opportunity provider and employer. [ABSTRACT FROM AUTHOR]

Heifers born to heifers have fewer primordial follicles in their ovaries at a year of age than heifers born to mature cows. We, therefore, hypothesized that heifers born to heifers would have decreased reproductive efficiency compared to heifers born to mature cows. Data were extracted from the USMARC database for replacement heifers (n = 7053) born between 2003 and 2010, representing 4631 dams. Ovaries were collected from neonatal (< 20 d) heifers born to heifers (n = 53) or heifers born to mature cows (n = 96) to examine influence of age of dam on follicle numbers immediately after birth. Data were analyzed using the MIXED procedure of SAS with age of dam as a class effect. For production data, dam was a random effect to account for dams having more than one daughter represented in the data. Heifers born to dams less than 6 years of age produced fewer calves than heifers born to cows greater than 5 years of age (5.2 ± 0.1 or 5.5 ± 0.1 calves, respectively; P < 0.0001). Heifers born to heifers weighed less at birth and weaning than heifers born to mature cows (P < 0.0001). Age of dam, however, did not influence number of antral follicles in the ovaries of neonatal heifers between heifers born to heifers and heifers born to mature cows (9.6 ± 1.4 and 8.0 ± 1.0; P = 0.36). As hypothesized, age of dam influences daughter reproductive performance; however, this does not appear to be completely driven by mechanisms associated with size of the ovarian reserve. Divergence in number of follicles in the ovaries does not occur until after 1 month of age, but this could be a carry-over effect of intra-uterine growth restriction in heifers born to heifers. USDA is an equal opportunity provider and employer. [ABSTRACT FROM AUTHOR]

Previous research demonstrated a favorable relationship between the number of follicles detectable in the bovine ovary by ultrasonography and fertility, and bovine females with diminished numbers of antral follicles had smaller reproductive tracts. Therefore, we hypothesized that uterine function would be compromised in beef heifers with diminished numbers of antral follilcles. Angus heifers (n = 480) were submitted for ultrasonographic evaluation of antral follicle number at 325 and 355 d of age. After the second ultrasonographic examination, 40 pubertal heifers with the greatest average number of antral follicles (30.9 ± 0.7) and 40 pubertal heifers with the lowest average number of antral follicles (14.2 ± 0.7) were synchronized with two i.m. injections of prostaglandin F 2α (25 mg) administered 11 d apart, and heifers were slaughtered on d 6 (n = 26 heifers/group) or d 16 (n = 14 heifers/group) of the resultant estrous cycle. The uterus was weighed, flushed for determination of protein content, and representative samples were fixed for determination of endometrial gland morphometry. Heifers in the Low group had fewer surface antral follicles and smaller reproductive tracts than heifers in the High group ( P < 0.01). Protein content of the uterine flushes was decreased in heifers in the Low group ( P < 0.01); however, there was no difference in the percent area of the endometrium occupied by endometrial glands. From these results, we conclude that the uterine environment of beef heifers with diminished numbers of antral follicles is less conducive to supporting early embryonic survival. [ABSTRACT FROM AUTHOR]

Increased antral follicles are associated with greater fertility and a uterine environment that is more supportive of early embryonic development in beef heifers. Glucose is a primary energy source for embryos, and glucose concentrations are elevated in uterine luminal fluid (ULF) of pregnant heifers. We hypothesized that ULF glucose concentrations and endometrial transcript abundance for glucose transporters on d16 after insemination would be greater in heifers with increased numbers of antral follicles. Heifers classified with either increased or diminished antral follicle counts were artificially inseminated following the CO-Synch protocol (d0). On d16 after insemination, reproductive tracts of heifers were collected at an abattoir to retrieve conceptuses to determine pregnancy. Uterine luminal fluid was collected, endometrium was biopsied, total RNA was extracted and glucose transporter transcript abundances were determined. Data were analyzed using the MIXED procedure of SAS with antral follicle group, pregnancy status, and the interaction as fixed effects. Glucose concentrations in ULF were greater in heifers with increased antral follicle numbers. Glucose ULF concentrations increased in pregnant heifers. Facilitated glucose transporter member 1 (SLC2A1) transcript abundance was increased in the endometrium of pregnant heifers but was not different due to antral follicle number or the interaction. Differences in uterine concentrations of glucose associated with antral follicle number could be due to another mechanism, since glucose transporters were not different between antral follicle numbers. Therefore, heifers with increased number of antral follicles have increased energy availability in the uterus to support trophoblast proliferation and function. • Increased antral follicles associated with greater uterine glucose concentrations. • Pregnancy status influences uterine glucose abundance at day 16 of gestation. • Antral follicle number does not impact abundance of glucose transporters. [ABSTRACT FROM AUTHOR]