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. 2024 Jan-Mar;50(1):94-105.
doi: 10.12865/CHSJ.50.01.13. Epub 2024 Mar 31.

Changes in Rat Mammary Tissue Architecture Following Pregnancy/Lactation Exposure to Glyphosate Alone or with 2,4-D and Dicamba

Andrei Eugen Cirstea  1 , Anca Oana Docea  2 , Liliana Cercelaru  3 , Andrei Ioan Drocas  4 , Robin Mesnage  5   6 , Cristina Marginean  7 , Cristian Marinas  8   9 , Magdalena Diaconu  1 , Kirill S Golokhvast  10 , Radu Mitrut  11 , Michael N Antoniou  5 , Aristidis Tsatsakis  12 , Daniela Calina  13
Affiliations

Changes in Rat Mammary Tissue Architecture Following Pregnancy/Lactation Exposure to Glyphosate Alone or with 2,4-D and Dicamba

Andrei Eugen Cirstea et al. Curr Health Sci J. 2024 Jan-Mar.

Abstract

The current study aimed to assess the possible endocrine disruptor effects on rat mammary tissue and reproductive organs during pregnancy and lactation when exposed to low doses of glyphosate and its combination with 2,4-dichlorophenoxyacetic acid (2,4-D) and dicamba. The study involved the exposure of pregnant Wistar rats to various regulatory-relevant doses of glyphosate, ranging from gestational day 6 until fine of the lactation period. Glyphosate doses corresponded to the European Union's glyphosate-acceptable daily intake (ADI; 0.5mg/kg bw/day) and no observed adverse effect level (NOAEL; 50mg/kg bw/day). The dose of the mixture of glyphosate, dicamba, and 2,4-D was at the European Union ADI for each herbicide namely 0.5, 0.002, and 0.3mg/kg bw/day, respectively. In the animals exposed to glyphosate NOAEL serum estradiol levels were increased compared to untreated animals, along with an upregulation of TNF-?, MMP-2, and MMP-9 as measured in mammary gland homogenates compared to non-treated animals. Moreover, in this group, a focally acute inflammatory infiltrate was observed in the mammary gland. Our study showed that short-term exposure to glyphosate at doses that are set as safe by regulators and thus without risk corroborated with a particular physiological state as gestation and lactation, can give rise to inflammatory changes in breast tissue in rats. These findings support the need for further evaluation of glyphosate and mixtures of glyphosate with other pesticides for public health protection, especially for those categories vulnerable to the potential endocrine disruptor properties of these pesticides such as pregnant women, newborns, and children.

Keywords: 2,4-D; Glyphosate; dicamba; mammary tissue toxicity; mixtures; pesticides.

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Conflict of interest statement

None to declare.

Figures

Figure 1
Figure 1
Ovary, HE staining, X200. A-Control group: ovarian follicles in different stages of evolution-blue arrow; B-Adi group: corpus luteus-blue arrow; C-Noael group: ovarian follicles in different stages of evolution-blue arrow; D-Mixt group: ovarian follicles in different stages of evolution-blue arrow, vascular hyperemia-green arrow
Figure 2
Figure 2
Salpinx, HE staining, X200. A-Control group; B-Adi group; C-Noael group: hyperplastic mucosa-blue arrow; D-Mixt group: atrophy and hypertrophy involving the mucosa-blue arrow
Figure 3
Figure 3
Uterine body/endometrium, myometrium, HE staining, X200. A-Control group: secretory-type mucosa-blue arrow, poorly represented vascular differentiation-green arrow; B-Adi group: simple cuboidal-cylindrical epithelium-blue arrow, rare endometrial glands-green arrow; C-Noael group: single layered cylindrical epithelium-blue arrow, proliferative phase glands-green arrow; D-Mixt group: vascular differentiation-blue arrow.
Figure 4
Figure 4
Mammary gland, HE staining, X200. A-Control group: glandular lactation changes-blue arrow, intralumenal eosinophilic secretion-green arrow; B-Adi group: atrophic acini-blue arrow; C-Noael group: fibrous stroma-blue arrow, mast cells-green arrow; D-Mixt group: lipomatous infiltration in the breast parenchyma-blue arrow, acinar hyperplasia with dilated acini-green arrow
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