Exposure to glyphosate-based herbicide during early stages of development increases insulin sensitivity and causes liver inflammation in adult mice offspring

Sandra Lucinei Balbo Corresponding author: Sandra Lucinei Balbo, Laboratório de Fisiologia Endócrina e Metabolismo, Rua Universitária, s/n – Universitário, Zip code: 85819-110 – Cascavel, PR, Brazil, Phone: (55 45) 3220-3257 E-mail: slbalbo@hotmail.com

Universidade Estadual do Oeste do Paraná, Cascavel, PR, Brazil.

https://orcid.org/0000-0002-2866-3928

Corresponding author: Sandra Lucinei Balbo, Laboratório de Fisiologia Endócrina e Metabolismo, Rua Universitária, s/n – Universitário, Zip code: 85819-110 – Cascavel, PR, Brazil, Phone: (55 45) 3220-3257 E-mail: slbalbo@hotmail.com

Conflct of interest: none.

AUTHORS’ CONTRIBUTION

Ellen Carolina Zawoski Gomes, Jakeline Liara Teleken and Rodrigo Vargas: carried out the experiment. Ellen Carolina Zawoski Gomes: wrote the manuscript with support from Jakeline Liara Teleken. Ana Claudia Paiva Alegre-Maller and João Paulo de Arruda Amorim: cosupervised the research. Maria Lúcia Bonfleur and Sandra Lucinei Balbo: conceived the original idea and supervised the project.

Parameters	CTRL	GBH	p value
Perigonadal fat (mg/mg body weight)^† † tudent’s t test. p value<0.05.	0.68±0.07	0.85±0.68	0.12
Pancreas (mg/mg body weight)^† † tudent’s t test. p value<0.05.	0.58±0.06	0.91±0.15	0.08
Extensor digitorum longus muscle (mg/mg body weight)^* * Mann-Whitney test	0.03±0.002	0.04±0.007	0.06
Soleus muscle (mg/mg body weight)^† † tudent’s t test. p value<0.05.	0.02±0.001	0.03±0.003	0.06
Glucose (mg/dL)^† † tudent’s t test. p value<0.05.	104.9±5.83	95.44±4.99	0.24
Insulin (ng/mL)^† † tudent’s t test. p value<0.05.	0.48±0.08	0.49±0.10	0.97
HOMA-IR^† † tudent’s t test. p value<0.05.	3.43±0,59	2.92±1.14	0.70
HOMA-β^† † tudent’s t test. p value<0.05.	79.14±21.85	93.68±30.73	0.71

Parameters	CTRL-F1	GBH-F1	p value
Body weight (g)^† † Student’s t test. p value<0.05.	25.03±0.36	23.63±0.74	0.06
Naso-anal length (cm)^* * Mann-Whitney test	9.28±0.08	9.06±0.13	0.16
Lee Index^† † Student’s t test. p value<0.05.	315.40±3.02	316.90±4.16	0.76
Retroperitoneal fat (mg)^† † Student’s t test. p value<0.05.	49.38±4.88	53.00±9.02	0.70
Perigonadal fat (mg)^† † Student’s t test. p value<0.05.	254.70±17.25	257.20±19.57	0.93
Brown adipose tissue (mg)^† † Student’s t test. p value<0.05.	76.13±4.31	66.57±7.33	0.25
Extensor digitorum longus muscle (mg)^* * Mann-Whitney test	10.88±1.12	10.33±0.76	0.64
Soleus muscle (mg)^* * Mann-Whitney test	13.69±3.79	9.12±1.39	0.20
Glucose (mg/dL)^† † Student’s t test. p value<0.05.	104.80±5.12	109.40±7.60	0.61
Insulin (ng/mL)^† † Student’s t test. p value<0.05.	0.25±0.03	0.29±0.05	0.42
HOMA-IR^* * Mann-Whitney test	1.52±0.15	1.60±0.23	0.73
HOMA-β^* * Mann-Whitney test	85.41±18.63	69.09±16.73	0.86

Histological feature	Definition	% in each category, according to group
Histological feature	Definition	Score/code	CTRL-F1 n=5 (%)	GBH-F1 n=5 (%)
Steatosis: Grade	Low to medium power evaluation of parenchymal involvement by steatosis
	<5%	0	100	100
	5%-33%	1	0	0
	>33%-66%	2	0	0
	>66%	3	0	0
Location	Predominant distribution
	Zone 3	0	0	0
	Zone 1	1	0	0
	Azonal	2	0	0
	Paracinar	3	0	0
Microvesicular steatosis	Continuous grouping
	Absent	0	100	100
	Present	1	0	0
Fibrosis: stage	None	0	100	100
	Perisinusoidal or periportal	1	0	0
	Middle, zone 3, perisinusoidal	1A	0	0
	Moderate, zone 3, perisinusoidal	1B	0	0
	Portal/periportal	1C	0	0
	Perisinusoidal and portal/periportal	2	0	0
	Bridging fibrosis	3	0	0
	Cirrhosis	4	0	0
Inflammation: lobular inflammation	Overall assessment of inflammatory foci
	No foci	0	100	20
	<2 foci per 200X field	1	0	60
	2-4 foci per 200X field	2	0	20
	>4 foci per 200X field	3	0	0
Liver cell injury: ballooning	None	0	100	100
	Few balloon cells	1	0	0
	Many cells/prominent ballooning	2	0	0

[1] Corresponding author: Sandra Lucinei Balbo, Laboratório de Fisiologia Endócrina e Metabolismo, Rua Universitária, s/n – Universitário, Zip code: 85819-110 – Cascavel, PR, Brazil, Phone: (55 45) 3220-3257 E-mail: slbalbo@hotmail.com

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Exposure to glyphosate-based herbicide during early stages of development increases insulin sensitivity and causes liver inflammation in adult mice offspring

ABSTRACT

Objective:

Methods:

Results:

Conclusion: