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Altered theca and cumulus oocyte complex gene expression, follicular arrest and reduced fertility in cows with dominant follicle follicular fluid androgen excess.

Summers AF, Pohlmeier WE, Sargent KM, Cole BD, Vinton RJ, Kurz SG, McFee RM, Cushman RA, Cupp AS, Wood JR - PLoS ONE (2014)

Bottom Line: We hypothesized that the steroid excess in follicular fluid of dominant follicles in High A4 cows would result in reduced fertility through altered follicle development and oocyte maternal RNA abundance.There was a tendency for reduction in stage 4 follicles in ovarian cortex samples from High A4 cows suggesting that progression to antral stages were impaired.These data suggest that the dominant follicle environment of High A4 cows including reduced estrogen conversion and androgen excess contributes to infertility in part through altered follicular and oocyte development.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal Science, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.

ABSTRACT
Aspiration of bovine follicles 12-36 hours after induced corpus luteum lysis serendipitously identified two populations of cows, one with High androstenedione (A4; >40 ng/ml; mean = 102) and another with Low A4 (<20 ng/ml; mean = 9) in follicular fluid. We hypothesized that the steroid excess in follicular fluid of dominant follicles in High A4 cows would result in reduced fertility through altered follicle development and oocyte maternal RNA abundance. To test this hypothesis, estrous cycles of cows were synchronized and ovariectomy was performed 36 hours later. HPLC MS/MS analysis of follicular fluid showed increased dehydroepiandrosterone (6-fold), A4 (158-fold) and testosterone (31-fold) in the dominant follicle of High A4 cows. However, estrone (3-fold) and estradiol (2-fold) concentrations were only slightly elevated, suggesting a possible inefficiency in androgen to estrogen conversion in High A4 cows. Theca cell mRNA expression of LHCGR, GATA6, CYP11A1, and CYP17A1 was greater in High A4 cows. Furthermore, abundance of ZAR1 was decreased 10-fold in cumulus oocyte complexes from High A4 cows, whereas NLRP5 abundance tended to be 19.8-fold greater (P = 0.07). There was a tendency for reduction in stage 4 follicles in ovarian cortex samples from High A4 cows suggesting that progression to antral stages were impaired. High A4 cows tended (P<0.07) to have a 17% reduction in calving rate compared with Low A4 cows suggesting reduced fertility in the High A4 population. These data suggest that the dominant follicle environment of High A4 cows including reduced estrogen conversion and androgen excess contributes to infertility in part through altered follicular and oocyte development.

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High A4 Cows Tend to have Reduced Numbers of Tertiary Follicles per Section.Follicles were classified and staged based on morphology (B) and counted on a per section basis to determine the effect of cow A4 classification on follicle growth and development. There was no difference in the number of primordial to secondary follicles (stage 0–3) between Low or High A4 cows (A). However, Low A4 cows tended to have a greater number of tertiary follicles (stage 4) compared with High A4 cows (A). †, P = 0.06.
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pone-0110683-g006: High A4 Cows Tend to have Reduced Numbers of Tertiary Follicles per Section.Follicles were classified and staged based on morphology (B) and counted on a per section basis to determine the effect of cow A4 classification on follicle growth and development. There was no difference in the number of primordial to secondary follicles (stage 0–3) between Low or High A4 cows (A). However, Low A4 cows tended to have a greater number of tertiary follicles (stage 4) compared with High A4 cows (A). †, P = 0.06.

Mentions: Given the differences identified in the dominant follicle of High A4 and Low A4 cows, additional phenotypes were measured in the ovariectomized cows and are summarized in Table 1. There was no difference (P = 0.57) in age for cows classified Low A4 compared with High A4 (4.31 vs. 4.75±0.61 years). After removal, ovaries were measured (length and width) and area calculated to determine the effect of A4 classification on ovarian size. There were no differences (P≥0.19) in follicle diameter, ovarian weight, theca or granulosa cell weight, or antral follicle count (AFC) based on A4 classification. However, the ratio of theca cells to granulosa cells (based on weight) was greater (P = 0.05) in High A4 compared to Low A4 cows (1.83 vs. 1.20±0.30). To determine differences in folliculogenesis within the ovarian cortex of cows from the Low and High A4 cows, hemotoxylin and eosin stained sections of ovarian cortex were analyzed to determine numbers of follicles at each stage of development. There was no difference in the number of follicles classified primordial, transitional, primary, or secondary (stages 0–3, Fig. 6A) between Low and High A4 cows. However, High A4 cows tended (P = 0.06) to have decreased numbers of follicles per section at stage 4 which are follicles no larger than 1 mm in diameter with a distinct antrum (Fig. 6A).


Altered theca and cumulus oocyte complex gene expression, follicular arrest and reduced fertility in cows with dominant follicle follicular fluid androgen excess.

Summers AF, Pohlmeier WE, Sargent KM, Cole BD, Vinton RJ, Kurz SG, McFee RM, Cushman RA, Cupp AS, Wood JR - PLoS ONE (2014)

High A4 Cows Tend to have Reduced Numbers of Tertiary Follicles per Section.Follicles were classified and staged based on morphology (B) and counted on a per section basis to determine the effect of cow A4 classification on follicle growth and development. There was no difference in the number of primordial to secondary follicles (stage 0–3) between Low or High A4 cows (A). However, Low A4 cows tended to have a greater number of tertiary follicles (stage 4) compared with High A4 cows (A). †, P = 0.06.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4199720&req=5

pone-0110683-g006: High A4 Cows Tend to have Reduced Numbers of Tertiary Follicles per Section.Follicles were classified and staged based on morphology (B) and counted on a per section basis to determine the effect of cow A4 classification on follicle growth and development. There was no difference in the number of primordial to secondary follicles (stage 0–3) between Low or High A4 cows (A). However, Low A4 cows tended to have a greater number of tertiary follicles (stage 4) compared with High A4 cows (A). †, P = 0.06.
Mentions: Given the differences identified in the dominant follicle of High A4 and Low A4 cows, additional phenotypes were measured in the ovariectomized cows and are summarized in Table 1. There was no difference (P = 0.57) in age for cows classified Low A4 compared with High A4 (4.31 vs. 4.75±0.61 years). After removal, ovaries were measured (length and width) and area calculated to determine the effect of A4 classification on ovarian size. There were no differences (P≥0.19) in follicle diameter, ovarian weight, theca or granulosa cell weight, or antral follicle count (AFC) based on A4 classification. However, the ratio of theca cells to granulosa cells (based on weight) was greater (P = 0.05) in High A4 compared to Low A4 cows (1.83 vs. 1.20±0.30). To determine differences in folliculogenesis within the ovarian cortex of cows from the Low and High A4 cows, hemotoxylin and eosin stained sections of ovarian cortex were analyzed to determine numbers of follicles at each stage of development. There was no difference in the number of follicles classified primordial, transitional, primary, or secondary (stages 0–3, Fig. 6A) between Low and High A4 cows. However, High A4 cows tended (P = 0.06) to have decreased numbers of follicles per section at stage 4 which are follicles no larger than 1 mm in diameter with a distinct antrum (Fig. 6A).

Bottom Line: We hypothesized that the steroid excess in follicular fluid of dominant follicles in High A4 cows would result in reduced fertility through altered follicle development and oocyte maternal RNA abundance.There was a tendency for reduction in stage 4 follicles in ovarian cortex samples from High A4 cows suggesting that progression to antral stages were impaired.These data suggest that the dominant follicle environment of High A4 cows including reduced estrogen conversion and androgen excess contributes to infertility in part through altered follicular and oocyte development.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal Science, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.

ABSTRACT
Aspiration of bovine follicles 12-36 hours after induced corpus luteum lysis serendipitously identified two populations of cows, one with High androstenedione (A4; >40 ng/ml; mean = 102) and another with Low A4 (<20 ng/ml; mean = 9) in follicular fluid. We hypothesized that the steroid excess in follicular fluid of dominant follicles in High A4 cows would result in reduced fertility through altered follicle development and oocyte maternal RNA abundance. To test this hypothesis, estrous cycles of cows were synchronized and ovariectomy was performed 36 hours later. HPLC MS/MS analysis of follicular fluid showed increased dehydroepiandrosterone (6-fold), A4 (158-fold) and testosterone (31-fold) in the dominant follicle of High A4 cows. However, estrone (3-fold) and estradiol (2-fold) concentrations were only slightly elevated, suggesting a possible inefficiency in androgen to estrogen conversion in High A4 cows. Theca cell mRNA expression of LHCGR, GATA6, CYP11A1, and CYP17A1 was greater in High A4 cows. Furthermore, abundance of ZAR1 was decreased 10-fold in cumulus oocyte complexes from High A4 cows, whereas NLRP5 abundance tended to be 19.8-fold greater (P = 0.07). There was a tendency for reduction in stage 4 follicles in ovarian cortex samples from High A4 cows suggesting that progression to antral stages were impaired. High A4 cows tended (P<0.07) to have a 17% reduction in calving rate compared with Low A4 cows suggesting reduced fertility in the High A4 population. These data suggest that the dominant follicle environment of High A4 cows including reduced estrogen conversion and androgen excess contributes to infertility in part through altered follicular and oocyte development.

Show MeSH
Related in: MedlinePlus