Decline in fertility with age has been well documented in women. There are ethical limitations to use humans as a model for basic research, and there is a lack of well characterized animal model. The objective was to characterize and validate a bovine model for the study of age-associated subfertility. All experiments were conducted on the same group of 13-14 year old cows (n=10), and their 1-4 year old young daughters (n=10). Mother-daughter pairs were used to reduce genetic variations. <p>Follicular wave pattern in a natural reproductive cycle was maintained in old cows similar to that in daughters. We hypothesized that aging in cattle is associated with elevated circulating concentrations of FSH, and reduced concentrations of steroid hormones. As stated, circulating FSH concentrations were higher (P=0.009) during follicular waves in old than young cows. The ovulatory follicle in 2-wave cycles was smaller in old cows (P=0.04), but plasma estradiol concentrations were higher (P=0.01). Luteal phase progesterone tended to be lower in old than young cows (P=0.1). The number of 4-5 mm follicles recruited into a follicular wave was lower (P<0.05) in old cows than in their daughters.<p>The response to ovarian synchronization and superstimulatory treatments was compared between old and young cows. We hypothesized that aging in cattle is associated with decreased synchrony of an induced follicular wave after steroid treatment. Conversely, the emergence of an induced follicular wave was synchronous between age groups. The preovulatory LH surge was delayed in old compared to young cows (P=0.01), but the detected ovulation times were not different. Old cows had fewer (P<0.01) follicles equal or greater than 6 mm after superstimulation, and tended (P=0.1) to have fewer ovulations than their daughters (32±4 versus 40 ±3, respectively). The response of individual cows to successive superstimulatory treatments was correlated (r>0.8; P<0.0001). <p>The hypothesis of reduced oocyte developmental competence in old cows was tested by comparing embryo production and pregnancy rates between old and young cows. Fewer (P=0.04) embryos were recovered from old cows (6±2) than their daughters (12±2). A higher proportion (P<0.01) of unfertilized oocytes and/or uncleaved zygotes were recovered from old cows (222/312, 71%) than their daughters (119/316, 38%). The recovery of fewer embryos in old cows suggests reduced oocyte developmental competence. The survival of embryos after transfer into unrelated young recipients was similar between age groups. <p>The effects of advanced age on oocyte meiotic maturation and oocyte chromosome numbers abnormalities were studied in old and young cows. Our hypothesis of compromised oocyte meiotic maturation with age was not supported; similar or higher proportion of metaphase II oocytes were recovered from old than young cows. The abnormalities of oocyte chromosomal numbers were similar between age groups. <p>To conclude, endocrine, follicular and oocyte developmental changes in old cows are consistent with those reported for women approaching menopause. Therefore, our results validated the use of a bovine model to study age-associated subfertility in women. Unlike women, we did not detect an age-related increase in abnormalities of oocyte chromosome numbers in cattle.

Decline in fertility with age has been well documented in women. There are ethical limitations to use humans as a model for basic research, and there is a lack of well characterized animal model. The objective was to characterize and validate a bovine model for the study of age-associated subfertility. All experiments were conducted on the same group of 13-14 year old cows (n=10), and their 1-4 year old young daughters (n=10). Mother-daughter pairs were used to reduce genetic variations. <p>Follicular wave pattern in a natural reproductive cycle was maintained in old cows similar to that in daughters. We hypothesized that aging in cattle is associated with elevated circulating concentrations of FSH, and reduced concentrations of steroid hormones. As stated, circulating FSH concentrations were higher (P=0.009) during follicular waves in old than young cows. The ovulatory follicle in 2-wave cycles was smaller in old cows (P=0.04), but plasma estradiol concentrations were higher (P=0.01). Luteal phase progesterone tended to be lower in old than young cows (P=0.1). The number of 4-5 mm follicles recruited into a follicular wave was lower (P<0.05) in old cows than in their daughters.<p>The response to ovarian synchronization and superstimulatory treatments was compared between old and young cows. We hypothesized that aging in cattle is associated with decreased synchrony of an induced follicular wave after steroid treatment. Conversely, the emergence of an induced follicular wave was synchronous between age groups. The preovulatory LH surge was delayed in old compared to young cows (P=0.01), but the detected ovulation times were not different. Old cows had fewer (P<0.01) follicles equal or greater than 6 mm after superstimulation, and tended (P=0.1) to have fewer ovulations than their daughters (32±4 versus 40 ±3, respectively). The response of individual cows to successive superstimulatory treatments was correlated (r>0.8; P<0.0001). <p>The hypothesis of reduced oocyte developmental competence in old cows was tested by comparing embryo production and pregnancy rates between old and young cows. Fewer (P=0.04) embryos were recovered from old cows (6±2) than their daughters (12±2). A higher proportion (P<0.01) of unfertilized oocytes and/or uncleaved zygotes were recovered from old cows (222/312, 71%) than their daughters (119/316, 38%). The recovery of fewer embryos in old cows suggests reduced oocyte developmental competence. The survival of embryos after transfer into unrelated young recipients was similar between age groups. <p>The effects of advanced age on oocyte meiotic maturation and oocyte chromosome numbers abnormalities were studied in old and young cows. Our hypothesis of compromised oocyte meiotic maturation with age was not supported; similar or higher proportion of metaphase II oocytes were recovered from old than young cows. The abnormalities of oocyte chromosomal numbers were similar between age groups. <p>To conclude, endocrine, follicular and oocyte developmental changes in old cows are consistent with those reported for women approaching menopause. Therefore, our results validated the use of a bovine model to study age-associated subfertility in women. Unlike women, we did not detect an age-related increase in abnormalities of oocyte chromosome numbers in cattle.