Reproductive Endocrinology

SUN-137 - Impact of Metformin Intervention on Fibrogenic Response in Genetically Diverse Outbred Mouse Models during Testicular Aging

Sunday, June 14, 2026

9:00 AM - 4:00 PM CT

Location: ENDOExpo; Poster Floor

Senior Author/Primary Investigator(s)

AC

Alina Cavallotti Gomez, MSc

Instituto de Biologa y Medicina Experimental (IBYME-CONICET)
Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina

Co-Author(s)

MR

Micaela Rozenblum, Student

Instituto de Biologa y Medicina Experimental (IBYME-CONICET)
Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina
YZ

Yun Zhu, PhD

Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL
Springfield, Illinois, United States
JM

Johanna Miquet, PhD

Instituto de Química y Fisicoquímica Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina
Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina
RC

Ricardo Calandra, PhD

Instituto de Biologa y Medicina Experimental (IBYME-CONICET)
Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina
AB

Andrzej Bartke, PhD (he/him/his)

Professor
Southern Illinois University School of Medicine
Springfield, Illinois, United States
RY

Rong Yuan, PhD

Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL
Springfield, Illinois, United States

Abstract Poster Presenter(s)

MM

María Eugenia Matzkin, PhD

Instituto de Biologa y Medicina Experimental (IBYME-CONICET)
Buenos Aires, ARGENTINA

Co-Author(s)

MM

María Eugenia Matzkin, PhD

Instituto de Biologa y Medicina Experimental (IBYME-CONICET)
Buenos Aires, ARGENTINA

Senior Author/Primary Investigator(s)

MF

Mónica Frungieri, PhD

Instituto de Biologa y Medicina Experimental (IBYME-CONICET)
Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina

The antidiabetic drug metformin (Met) has been proposed as an anti-aging agent however, its effects on the testis remain controversial. Fibrosis, a process associated with an increase in collagen expression and deposition in the extracellular matrix, is a hallmark of aging tissues.
Here, we investigated the impact of Met supplementation on fibrosis during testicular aging in two genetically diverse, outbred mouse models. On the one hand, Diversity Outbred (DO) male mice received standard (std) diet or Met (0.1 % w/w) diet ad libitum from 2-month-old to 19-month-old. On the other hand, male UM-Het3 mice were exposed to a daily early life intervention (ELI) with saline or Met (i.p. 200 mg/kg/day) starting at the age of 15 days, for 40 days and, subsequently fed a high fat diet (HFD, 60 Kcal% Fat from Research Diets) up to 11 months of age.
In picrosirius red-stained testicular sections (a histological technique used to visualize collagen fibers), Met significantly increased the percentage of collagen deposition in testicular parenchyma (%Col: mean ± S.E.M., (n); std diet: 2.86 ± 0.14, (9); Met diet: 3.67 ± 0.35, (7); p< 0.05) as well as the thickness of the seminiferous tubules’ wall (µm; mean ± S.E.M., (n); std diet: 1.19 ± 0.04, (10); Met diet: 1.40 ± 0.02, (7); p< 0.05) in 19-month-old DO mice (p < 0.05).
As expected, HFD impaired glucose tolerance and significantly increased body weight in UM-Het3 mice (p < 0.05). In addition, feeding a HFD to UM-Het3 mice altered the organization of collagen fibers and significantly increased testicular fibrosis (p < 0.05), but surprisingly, in those mice that received metformin ELI, a marked reduction of %Col (mean ± S.E.M., (n); saline + HFD: 5.92 ± 0.33, (13); Met ELI + HFD: 3.92 ± 0.30, (15); p< 0.05) and tubular wall thickening (µm; mean ± S.E.M., (n); saline + HFD: 1.15 ± 0.04, (13); Met ELI + HFD: 0.88 ± 0.04, (15); p< 0.05) was detected.
In brief, our studies indicate that long-term Met treatment seems to show a negative effect on testicular fibrosis during aging in healthy (non-obese/non-diabetic) individuals. Instead, Met ELI, particularly in pre-diabetic/obese mice, might exert beneficial effects on testicular collagen deposition and tubular wall thickness, reducing tissue damage and, therefore, the decline of male reproductive function in the aging process. Nevertheless, at this point in our research, we cannot rule out differences between strains.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*