Abstract

Infertility and subfertility are important and pervasive reproductive problems in both domestic animals and humans. The majority of embryonic loss occurs during the first three weeks of pregnancy in cattle and women due, in part, to inadequate endometrial receptivity for support of embryo implantation. To identify heifers of contrasting fertility, serial rounds of artificial insemination (AI) were conducted in 201 synchronized crossbred beef heifers. The heifers were then fertility classified based on number of pregnancies detected on day 35 in four AI opportunities. Heifers, classified as having high fertility, subfertility or infertility, were selected for further study. The fertility-classified heifers were superovulated and flushed, and the recovered embryos were graded and then transferred to synchronized recipients. Quantity of embryos recovered per flush, embryo quality, and subsequent recipient pregnancy rates did not differ by fertility classification. Two in vivo-produced bovine embryos (stage 4 or 5, grade 1 or 2) were then transferred into each heifer on day 7 post-estrus. Pregnancy rates were greater in high fertility than lower fertility heifers when heifers were used as embryo recipients. The reproductive tracts of the classified heifers were obtained on day 14 of the estrous cycle. No obvious morphological differences in reproductive tract structures and histology of the uterus were observed in the heifers. Microarray analysis revealed differences in the endometrial transcriptome based on fertility classification. A genome-wide association study, based on SNP genotyping, detected 7 moderate associations with fertility across 6 different chromosomes. Collectively, these studies support the idea that innate differences in uterine function underlie fertility and early pregnancy loss in ruminants. Cattle with defined early pregnancy success or loss is useful to elucidate the complex biological and genetic mechanisms governing endometrial receptivity and uterine competency for pregnancy.

Highlights

  • Infertility and subfertility are important and pervasive problems in both domestic animals and humans, and the greatest limitation to reproductive efficiency across mammalian species is embryonic mortality [1]

  • Embryo mortality is greater in non-lactating cows than heifers [7], and early pregnancy loss is even greater in high producing lactating dairy cattle and can approach 70% [2,10,11]

  • Pubertal crossbred beef heifers (n = 201) were given four opportunities to establish pregnancy using ovulation synchronization and artificial insemination (AI) followed by pregnancy determination on day 35 (Fig. 1)

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Summary

Introduction

Infertility and subfertility are important and pervasive problems in both domestic animals and humans, and the greatest limitation to reproductive efficiency across mammalian species is embryonic mortality [1]. Embryo mortality is greater in non-lactating cows than heifers [7], and early pregnancy loss is even greater in high producing lactating dairy cattle and can approach 70% [2,10,11]. Infertility and subfertility are major cost factors in the cattle embryo transfer industry [12]. The failure to establish pregnancy in humans and animals is due to both embryonic and maternal factors [13,15,16]. Knowledge of the complex biological and genetic mechanisms governing endometrial receptivity and conceptus implantation is limited in both domestic ruminants and humans [17]

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