Characterization of anogenital distance and its relationship to fertility in lactating Holstein cows

Abstract

Anogenital distance (AGD) serves as a marker for prenatal androgenization, reproductive development, and fertility in humans and rodents. The primary objectives of this observational study in lactating dairy cows were to (1) characterize the distribution and variability of AGD, (2) determine the relationship among AGD and potential postnatal AGD determinants of age and height, and (3) evaluate the associations between AGD and pregnancy to first artificial insemination (P/AI) and cumulative pregnancy by 250 d in milk (DIM) within parity groups (first, second, and third+ parities). The secondary objective was to evaluate the association between AGD and testosterone concentrations. The AGD (mm), age (yr), and height at hip (cm) at the time of AGD determination, and aforesaid reproductive outcomes were determined in 921 Holstein cows (first, second, and third+ parity; n = 360, 256, and 305, respectively). Plasma concentrations of testosterone were determined in a subset of 93 cows. Overall, AGD had a normal distribution and high variability [mean (±standard deviation); 131.0 ± 12.2 mm], was weakly associated with cow age and height (coefficient of determination = 0.09 and 0.04, respectively), and had an inverse relationship with P/AI in first- and second-parity cows, but not in third+ parity cows. For every 1 mm increase in AGD, the odds of P/AI decreased by 3.4 and 2.4% for first- and second-parity cows, respectively. The optimal AGD threshold to predict probability of P/AI was 127.1 mm for both first- (sensitivity: 66.4; specificity: 56.6%) and second-parity cows (sensitivity: 46.0; specificity: 70.4%). Accordingly, first- and second-parity cows were categorized into either short or long AGD (≤ or >127.1 mm), and associations with reproductive outcomes were evaluated. First-parity cows with long AGD had lower P/AI (30.9 vs. 53.6%) and decreased likelihood (hazard ratio: 0.68) of pregnancy by 250 DIM than those with short AGD. Similarly, second-parity cows with long AGD had reduced P/AI (28.3 vs. 44.4%) and a tendency for decreased likelihood (hazard ratio: 0.76) of pregnancy by 250 DIM than in cows with short AGD. The association between AGD and testosterone was weak and nonsignificant. In summary, AGD in Holstein cows was normally distributed, highly variable, and weakly associated with age and height. Besides, AGD had an inverse relationship with P/AI and cumulative pregnancy by 250 DIM in first- and second-parity cows; however, such a relationship was not evident in older (third+ parity) cows.

The relationship between anogenital distance and fertility, and genome-wide associations for anogenital distance in Irish Holstein-Friesian cows

“…In agreement with the current findings, our previous study (Gobikrushanth et al, 2017) reported that phenotypic variation in AGD was weakly associated with age (R 2 = 0.09) and height (R 2 = 0.04) in Canadian Holstein cows. Similarly, either weak or nonsignificant associations were reported between AGD and length and BW in female infants (Thankamony et al, 2009) and age, height, and BW in young women (Mendiola et al, 2012;Mira-Escolano et al, 2014b;Wu et al, 2017).…”

“…Overall, AGD had a normal distribution and high variability in Irish Holstein-Friesian cows managed under pasture-based, seasonal-calving systems (mean ± SD: 119.2 ± 11.6 mm; Table 1 and Figure 1). The pattern of distribution and variability reported herein was comparable to that of our previous study (Gobikrushanth et al, 2017) in Canadian Holstein cows Figure 2. Association between anogenital distance and age, height at hip, BW, and BCS in a subset of 281 Irish Holstein-Friesian cows (a; R 2 = 0.09; P < 0.01, b; R 2 = 0.06; P < 0.01, c; R 2 = 0.10; P < 0.01, d; R 2 = 0.02; P < 0.01).…”

“…The relationship between anogenital distance and fertility, and genome-wide associations for anogenital distance in Irish Holstein-Friesian cows M. Gobikrushanth, 1,2 D. C. Purfield, 2 J. Kenneally, 2 R. C. Doyle, 2 S. A. Holden, 2 P. M. Martinez, 2 E. Rojas Canadas, 2 T. C. Bruinjé, 1 M. G. Colazo, 3 D. J. Ambrose, 1,3 and S. T. Butler 2 * 1703 AGD was normally distributed, highly variable, minimally influenced by postnatal factors such as age and height, and inversely related to pregnancy to first and subsequent insemination events in first-and secondparity Canadian Holsteins cows (Gobikrushanth et al, 2017). In this regard, first-and second-parity Canadian Holstein cows with long AGD (>127.1 mm) had lower conception rate to first AI (first parity: 30.9 vs. 53.6%; second parity: 28.3 vs. 44.4%) and decreased likelihood of pregnancy by 250 d in milk (hazard ratio of 0.68 for first parity and 0.76 for second parity) compared with cows with short AGD (≤127.1 mm).…”

“…Anogenital distance (AGD) has been defined as the distance from the center of the anus to either the posterior fourchette (Salazar-Martinez et al, 2004) or the clitoris (Sathyanarayana et al, 2010) in women, and to the base of the clitoris in dairy cows (Gobikrushanth et al, 2017). Prenatal exposure of female fetuses to excess androgen leads to androgenization of the reproductive system in utero (Bowman et al, 2003;Sadler, 2012), which results in greater AGD and poor postnatal fertility outcomes in mice (Zehr et al, 2001), rabbits (Bánszegi et al, 2012), gilts (Drickamer et al, 1997), and women (Mendiola et al, 2012;Mira-Escolano et al, 2014a;Wu et al, 2017).…”

“…We hypothesized that seasonal-calving, pasture-based cows in Ireland with short AGD have greater fertility performance than cows with long AGD, as observed in Canadian Holstein cows (Gobikrushanth et al, 2017), and that SNP associated with phenotypic variation in AGD could be identified. Therefore, the objectives of this observational study were to (1) characterize the distribution and variability of AGD, (2) determine the factors associated with AGD, (3) estimate heritability for AGD, (4) identify SNP associated with phenotypic variation of AGD, and (5) validate the association between categories of AGD and fertility in Irish Holsteins.…”