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Unexplained repeated pregnancy loss is associated with altered perceptual and brain responses to men’s body-odor

  1. Liron Rozenkrantz
  2. Reut Weissgross
  3. Tali Weiss
  4. Inbal Ravreby
  5. Idan Frumin
  6. Sagit Shushan
  7. Lior Gorodisky
  8. Netta Reshef
  9. Yael Holzman
  10. Liron Pinchover
  11. Yaara Endevelt-Shapira
  12. Eva Mishor
  13. Timna Soroka
  14. Maya Finkel
  15. Liav Tagania
  16. Aharon Ravia
  17. Ofer Perl
  18. Edna Furman-Haran
  19. Howard Carp
  20. Noam Sobel  Is a corresponding author
  1. Department of Neurobiology, Weizmann Institute of Science, Israel
  2. The Azrieli National Institute for Human Brain Imaging and Research, Israel
  3. Department of Otolaryngology & Head and Neck Surgery, Edith Wolfson Medical Center, Israel
  4. Life Sciences Core Facilities, Weizmann Institute of Science, Israel
  5. Department of Obstetrics & Gynecology, Sheba Medical Center, Israel
Research Article
Cite this article as: eLife 2020;9:e55305 doi: 10.7554/eLife.55305
5 figures and 3 additional files

Figures

Women with uRPL can identify their spouse by smell.

(a) A custom-designed Shirt Sniffing Device (SSD) to standardize body-odor sampling. The SSD consists of a glass jar containing the T-shirt, with an air intake port via soda lime filter, and air sampling port via one-way flap valve into individual-use airtight nose mask. This arrangement assured that environmental odors didn't contaminate the sample during the sampling process. The recognizable person in the figure is a co-author and not a participant. (b) Performance at 3AFC identification test (n = 66). uRPL women in purple, control women in green. Bar graphs depict group means, each dot represents a participant, dots are jittered to prevent overlay, error bars are s.e.m, **p<0.01. Black dashed line indicates chance level. (c) Bootstrap analysis. Gray lines represent the 10,000 repetitions; the purple line represents the actual uRPL-control difference value.

Women with uRPL have slightly better olfaction than controls.

uRPL (purple) and control (green) women were tested for various olfactory facets. (a) Percent accuracy at every-day odorant identification (n = 76). (b) Percent accuracy at monomolecule discrimination (EST, ANN, AND) (n = 76). (c) DMTS threshold (n = 36). (d) A composite score of identification, discrimination and threshold (n = 78). (e) Bootstrap test of ‘d’, 10,000 repetitions, the purple line represents the actual uRPL-control difference value. Bar graphs depict means, each dot represents a participant, dots are jittered to prevent overlay, error bars are s.e.m. *p<0.05. Black dashed line indicates chance level.

Figure 2—source data 1

All odourant identification, discrimination, and detection values, including composite score.

https://cdn.elifesciences.org/articles/55305/elife-55305-fig2-data1-v1.xlsx
Figure 3 with 1 supplement
Women with uRPL have altered perception of men's body-odor.

(a) uRPL (purple) and control (green) women ratings of non-spouse men body-odor, score combines ratings of pleasantness, sexual attraction, intensity and fertility attributed to the odor (see separate ratings in Figure 3—figure supplement 1). n = 36. Bar graphs depict means, each dot represents a participant, dots are jittered to prevent overlay, error bars are s.e.m. *p<0.05. (b) Bootstrap test of the non-spouse result, 10,000 repetitions, the purple line represents the actual uRPL-control difference value.

Figure 3—source data 1

All perceptual ratings of blank, non-spouse, and spouse.

https://cdn.elifesciences.org/articles/55305/elife-55305-fig3-data1-v1.xlsx
Figure 3—figure supplement 1
Altered perception of men’s body-odor in uRPL.

Eighteen women with uRPL and 18 controls rated men’s body-odors of three kinds: An unworn t-shirt (Blank), a non-spouse male, and their actual spouse; on four traits: (a) Intensity; (b) Pleasantness; (c) Sexual attraction; and (d) Fertility. A multivariate RM ANOVA of Group (uRPL/Control), Odor (Blank/Non-Spouse/Spouse) and Descriptor (Intensity/Pleasantness/Sexual attraction/Fertility) revealed a main effect of Descriptor (F(3,102) = 12.4, p<0.001), reflecting that traits were applied differently, regardless of group and odor (mean Intensity: 0.49 ± 0.21, mean Pleasantness: 0.42 ± 0.14, mean Sexual attraction: 0.33 ± 0.15, mean Fertility: 0.38 ± 0.15; all pairwise comparisons t(35) > 2.12, all p<0.041, all Cohen’s d > 0.35). In addition, a significant interaction of Odor x Descriptor (F(6,204) = 8.27, p<0.001) was carried by intensity ratings alone (F(2,70) = 15.8, p<0.001; all other descriptors: all F(2,70) < 1.93, all p>0.15). This intensity difference was carried solely by differences from Blank, which was, unsurprisingly, less intense than all other otherwise (and importantly) equally-intense stimuli (mean Intensity ratings: Blank:=0.31 ± 0.26, Non-Spouse = 0.58 ± 0.23, Spouse:=0.59 ± 0.35. Blank vs. Non-Spouse and Spouse: Both t(35) > 4.7, both p<0.001, both Cohen’s d > 0.77; Non-Spouse vs Spouse: t(35) = 0.15, p=0.88, Cohen’s d = 0.03). Finally, a significant interaction of Group x Odor (F(2,68) = 3.43, p=0.038) reflected a lower rating for Non-Spouse among uRPL versus control women. This effect that materialized in the combined descriptors was mostly carried by fertility ratings, evident by independent tests between groups for Non-Spouse ratings (Pleasantness: t(34) = 1.6, p=0.12, Cohen’s d = 0.53, nonparametric Mann-Whitney = 213.5, p=0.107; Attraction: t(34) = 1.53, p=0.135, Cohen’s d = 0.51, nonparametric Mann-Whitney = 214, p=0.104; Fertility: t(34) = 2.69, p=0.011, Cohen’s d = 0.9, nonparametric Mann-Whitney = 245, p=0.009; Intensity was not statistically significant: t(34) = 1.09, p=0.28, Cohen’s d = 0.36, nonparametric Mann-Whitney = 187, p=0.44). Bar graphs depict means, each dot represents a participant, dots are jittered to prevent overlay, error bars are s.e.m.

Figure 4 with 1 supplement
Women with uRPL have smaller olfactory bulbs and shallower olfactory sulci.

(a) Olfactory bulb volume. A 3D reconstruction of uRPL (purple) and control (green) participants’ left (upper row of the two) and right (bottom row) olfactory bulbs. Bulbs sorted by size (see Figure 4—figure supplement 1 for sort by participant (uRPL to Control) match). Note that the reconstructions do not relate to the values on the Y axis, the values are reflected in the data lines alone. (b) Bootstrap test of ‘a’, 10,000 repetitions, the purple line represents the actual uRPL-control difference value. (c) Olfactory sulci depth (right, left and average) of uRPL (purple bars) and control (green bars) participants. (d) Bootstrap test of the average in ‘c’, 10,000 repetitions, the purple line represents the actual uRPL-control difference value. Bar graphs depict means, each dot represents a participant, dots are jittered to prevent overlay. Error bars are s.e.m. *p<0.05. (e) The relation between olfactory composite scores and olfactory bulb volumes for uRPL (purple) and control (green) participants. n = 46. Each square (uRPL) and triangle (control) represent a participant.

Figure 4—figure supplement 1
Smaller olfactory bulbs in uRPL.

Women with uRPL have significantly smaller olfactory bulbs (Right bulb volume: uRPL: 45.9 ± 12 mm3, control: 55.4 ± 9.7 mm3, t(44) = 2.96, p=0.005, Cohen’s d = 0.87; Left bulb volume: uRPL: 46.4 ± 8.9 mm3, control: 55.7 ± 9.4 mm3, t(44) = 3.45, p=0.001, Cohen’s d = 1.02; Average bulb volume: uRPL: 46.1 ± 9.9 mm3, control: 55.5 ± 9 mm3, t(44) = 3.37, p=0.0016, Cohen’s d = 0.99). This figure shows a 3D reconstruction of uRPL (purple) and control (green) participants’ left and right olfactory bulbs (volumes). Bulbs sorted by match of uRPL and control participants (see main text and Figure 4—source data 1 for details about the matching).

Figure 5 with 1 supplement
Women with uRPL have an altered brain response to male body-odor.

(a) Hypothalamus blood-oxygen level-dependent (BOLD) activity in uRPL (non-spouse >blank), compared to control. (b) Whole brain PPI test, reflecting greater correlation with hypothalamus (seed ROI) time series for all emotionally-weighted-movie-clips>fixation. Both scatterplots reflect the % signal change of each participant (uRPL in purple, controls in green). The diagonal is the unit slope-line (x = y). Dots above the slop line represent higher % signal change for Non-Spouse men body odor, and dots below the line represent higher % signal change for Blank. n = 46. All coordinates in MNI space.

Figure 5—figure supplement 1
Reduced gray matter volume in the right fusiform in uRPL.

For voxel-based morphometry we compared structural data from 23 uRPL and 23 control women using FSL-VBM. The threshold for significance is p<0.0001, without correction for multiple comparisons. A single locus materialized in the right fusiform.

Additional files

Supplementary file 1

Participants.

A table of all uRPL and Control women who participated in the project, including their age, number of pregnancies, number of repeated pregnancy losses (if any) and number of living children.

https://cdn.elifesciences.org/articles/55305/elife-55305-supp1-v1.xlsx
Supplementary file 2

Spouse identification results.

An extended table for ‘Figure 1—source data 1' containing the success rates at the spouse identification task, with the first two trials, first four trials, and all trials per participant.

https://cdn.elifesciences.org/articles/55305/elife-55305-supp2-v1.xlsx
Transparent reporting form
https://cdn.elifesciences.org/articles/55305/elife-55305-transrepform-v1.pdf

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