Organochlorine and Organophosphate Pesticides Exposure and Female Reproductive Disorder

Literature Search Approaches

The authors reviewed scientific literature published in PubMed, Scopus, MEDLINE, the Web of Science database, Google Scholar, and ScienceDirect to identify studies pertinent to the article. They utilized specific keywords using Medical Subject Headings (MeSH) from the PubMed database, such as “Pesticide”, “Exposure” (“Pesticides adverse effects” or “Pesticides poisoning” or “Pesticides toxicity”), “Infertility”, “Endocrine disruptors”, “Organochlorine”, “Organophosphate”, “Reproductive Health”, and “Hypothyroidism” to carry out a targeted and extensive search using Boolean operators “AND”, and “OR”. This review article provides comprehensive and up-to-date information on the scientific literature on OCPs and OPPs exposure and its relation to female reproductive health issues.

Inclusion and Exclusion Criteria

Study Identification

SA and MKA independently screened the studies based on predefined guidelines encompassing study characteristics and design. Duplicate records were removed both automatically using Zotero reference management software and manually. The authors, NGA and SD, then screened the titles and abstracts, followed by a rigorous full-text review to confirm eligibility. Any discrepancies were settled via consultation with a senior expert (AAM) to ensure a unified decision.

Data Retrieval

The authors established specific and clear criteria for studies included in this review, such as publication year, study design, sex, dosage/intensity, OCPs and OPPs exposure, participant demographics, analytical methods, metabolic disorders, thyroid effects, infertility, and outcome measures. In many environmental health studies, authors don’t evaluate the article only based on "exposed" vs. "unexposed."

Risk-of-Bias and Study Quality Assessment

Three different authenticated frameworks were used: Modified Newcastle-Ottawa Scale (NOS), the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE), and the National Toxicology Program/Office of Health Assessment and Translation (NTP/OHAT). Two reviewers (SA and AAM) examined independently the methodological quality and potential risk of bias of all included research studies. The NOS was used to assess the quality of case-control and cross-sectional studies. Each study was graded based on how participants were selected, how comparable the groups were, and how exposure and outcomes were measured. According to our inclusion criteria, studies that used validated biomonitoring of OCPs and OPPs levels in blood, urine, or breast milk, truly representative cases, and controls for key confounders (reproductive age, BMI) received higher-quality scores. Self-selected volunteers, with no adjustment for confounding, received low scores.

For in vivo animal studies, we used the SYRCLE risk of bias tool to assess areas such as selection bias (e.g., random housing), performance bias (e.g., blinding of researchers), and detection bias. In vitro mechanistic studies followed NTP/OHAT guidelines. We focused on the use of suitable control groups, the purity and stability of the OCPs/OPPs, and the consistency of dosage and exposure duration.

Search Result and Study Characteristics

This study incorporates both older and newer studies within this broad timeframe, with research published between 1984 and 2026. The databases were last searched on 10 February 2026. In the broader search, a systematic literature search identified 1488 articles from electronic databases and gray literature sources. 1417 articles were remained after removing duplicate records (n = 9) and ineligible records (n = 62) identified by automated tools. After systematic screening of titles and abstracts, including epidemiological studies, in vivo, and in vitro experiments, reviews, conference abstracts, and articles unrelated to the research topics, 1275 articles were removed. A total of 213 studies met eligibility criteria (Fig. 2), and the remaining 36 articles were removed for not being published in English (n=5), being editorial or commentary articles (n=9), lacking extractable data (n=18), or being conference abstracts (n=4). A total of 177 studies were included, of which eight were cross-sectional, three were case-control, five were in vivo, and one was in vitro. Overall, cross-sectional study designs dominate the literature.

Figure 2.

PRISMA flow chart detailing the identification, screening, and inclusion of studies from electronic database searches.

Global Distribution and Consumption of Pesticides

Pesticides are widely used as an effective and cost-efficient way to increase crop production and yield in the modern agricultural system to ensure food security for the ever-growing population. Globally, the annual utilization of pesticides was almost 2 million tonnes (mt) by 2020. However, in the year 2022, as compared to 2021, total pesticide consumption increased by 4% and reached up to 3.7 mt. Over the past decade, there has been an approximate 13% increase, along with a doubling of pesticide consumption since 1990. Asia comprised the largest share of global insecticide consumption at 38%, while Europe had the lowest at 13%. Brazil was the major consumer of pesticides, with 801 kilo tonnes (kt) in 2022, which was approximately 70% higher than the United States of America (468 kt), the second-largest consumer in the world. The other countries ranking after that, based on pesticide usage, were represented in Fig. 3. [42].

Figure 3.

The Scale of Global Pesticide Consumption

Human Exposure to OCPs and OPPs

People are exposed to OCPs and OPPs due to the accumulation in the body and regular intake of contaminated food and dust (43). This exposure is assessed using the 'Estimated Daily Intake' (EDI) to determine overall health risks (44). In periurban areas of Delhi, India, the daily dietary OCPs exposure from vegetable consumption was found to be significantly higher for children (mean EDI of 4.25 × 10^-5 mg/kg/day) compared to adults (2.19 10^-5 mg/kg/day) (45). The EDI of OCPs reported for residents in Kandal province, Cambodia, was 3.3 × 10^-4 mg/kg/day (46). The concentrations of OCPs and other pesticides were monitored in food products (meat, fish, and dairy) of the Danish population, and the average daily intake of OCPs was estimated at between 0.03 and 0.3 μg/day (47). In another study from Gujranwala, Pakistan, DDTs were recognized as the primary environmental pollutant in air, soil, and cereal crops. The EDI from rice and wheat (3.9 × 10-5 - 4.0 × 10^-5 mg/kg/day) exceeded safety limits. Ultimately, the findings indicated a severe health risk to the local population due to the ingestion of these contaminated staple foods (48). OPP concentrations in artesian wells and the ingestion of contaminated water in the agricultural and non-agricultural groups in Bang Reing sub-district, Thailand, were studied during both wet and dry seasons. The ingestion of OPP from drinking water was estimated, with concentrations of 0.187 and 0.919 μg/day in agricultural communities during the dry and wet seasons, respectively, and 0.008 μg/day in the non-agricultural communities during both seasons. The average OPPs concentration in the agronomic communities' artesian wells (0.085 and 0.418 μg/l in dry and wet seasons) was higher than in the non-agricultural communities (49).

The data show a clear trend that children and people living in agricultural areas, especially during wet seasons when runoff occurs, face the highest toxic risk. While daily intake levels were low in Denmark, as compared to those in Southeast Asia and India, they are significantly closer to, or exceed, international safety thresholds. In many developing countries, the absence of strict pesticide-use guidelines and the reuse of banned persistent chemicals lead to EDIs that often exceed these levels (50, 51).

Toxic Legacy of Pesticides and their Exposure on Female Health

Although pesticides are crucial for crop protection and enhancing production, widespread application of pesticides can pose harmful consequences due to their bioaccumulation and persistence in the environment. Pesticides pollute the overall ecosystem directly and indirectly, which causes toxicity and health hazards for humans and the environment [52]. Previous research studies have reported that approximately 90% of pesticides used in the farming field end up having results that can be toxic to the ecological system [53, 54]. According to Van der et al., excessive use of pesticides contaminates soil and water, harming microflora and microfauna and inhibiting plants from absorbing vital mineral elements [55]. One of the main issues for environmentalists is that pesticides seep into groundwater and pollute drinking water [56].

According to a WHO report, due to the severity of pesticide toxicity influenced by exposure time and concentration, approximately 300,000 people die each year worldwide [57]. In general, the body eliminates pesticides and other toxicants through excretory glands. However, the long-term consumption of fruits and vegetables cultivated in pesticide-contaminated soil and water results in toxin accumulation in various organs, contributing to chronic diseases such as asthma, reproductive disorders, neurotoxicity, diabetes, cancer, heart disease, and necrosis [58]. Numerous scientific studies have documented accidental pesticide poisoning in humans due to ingestion or inhalation.

Female reproductive development and function depend upon concentrations and equilibrium of endocrine hormones. Dysfunction of the endocrine system is the consequence of an imbalance of reproductive hormone and, and these irregularities may be caused by modulating estrogens, thecal androgens, and thyroid hormone concentrations. There are many OCPs, such as methoxychlor (MXC), p,p′-dichloro-diphenyl-trichloroethane (DDT), chlordane, endosulfan, HCH (hexachlorocyclohexane), heptachlor, and hexachlorobenzene (HCB), that negatively affect women’s lactation ability and infant health [59].

Bedi et al. documented the identification of various pesticide metabolites in women's breast milk samples (n = 53) from rural and urban donors in Punjab, India, using gas chromatography-mass spectrometry (GC-MS). The identified pesticides included β-HCH, γ-HCH, endrin, DDT, and its metabolites p,p′-dichloro-diphenyl-dichloroethylene (DDE) and p,p′-dichloro-diphenyl-dichloroethane (DDD), with mean concentrations of 97.9, 101.7, 90.7, 100.3, 1574.1, and 239.8 ng g−1 lipid wt., respectively. However, the reported estimated level of DDT residues was higher than the allowable tolerable daily intake limit as per the guidelines of FAO/WHO for a few infants. However, there was no significant association found with the BMI of subject donors with total HCH and total DDT. Additionally, metabolites of β-endosulfan, endosulfan sulphate, endrin, chlorpyrifos, and cypermethrin were also found in the breast milk specimen [60]. In another study, Bedi et al. detected pesticide metabolites in blood samples from individuals working in the cotton belt of Punjab; out of 50 blood samples, 6 were women, and commonly found pesticides included p,p’-DDE, p,p’-DDD, o,p’-DDE, and β-endosulfan at a mean concentration of 15.26, 2.71, 5.62, and 4.02 ng/ml, respectively. The findings also indicated that certain characteristics among subjects, such as older people, non-vegetarian dietary habits, and regular pesticide spraying, were also associated with higher pesticide loads. For example, higher levels of total DDT residues were analyzed in non-vegetarian subjects (27.21 ng/ml) as compared to vegetarian subjects (16.61 ng/ml) [61]. A pilot screening study was performed in Haryana, India, to detect OCPs, OPPs (GC-MS), and pyrethroids (GC-electron capture detector). p,p’-DDT, and p,p’-DDE pesticide residues were analyzed in women's breast milk samples (n=75) at levels reaching up to 4% (range: < LOQ–107 μg/l) [62]. Dewan et al. conducted a study at a tertiary hospital in Delhi, India, in 2009 and 2010, and OCPs residues were detected by Chromatograph equipped with ⁶³Ni Electron Capture Detector in breast milk samples, placenta, maternal, and cord blood samples, and reported the highest concentration of pesticide metabolites was detected in maternal blood while umbilical cord blood exhibited lower levels, which demonstrated that mothers have the highest load of OCPs and continued partial transfer of such residues to their fetuses [63].

Another study performed in southern Taiwan (n = 68) from 2013 to 2016, to detect OCP residues in breast milk samples, using a high-resolution gas chromatography with low-resolution mass spectrometry (HRGC/LRMS) instrument. The geometric mean concentrations of ΣDDT and ΣHCH were reported as 9.81 ± 7.52 ng⁻¹ lipid⁻¹ and 0.539 ± 0.557 ng⁻¹·lipid⁻¹, respectively. The study revealed that specific sociodemographic factors, primarily annual family income and number of pregnancies (gravidity), correlated with OCPs levels, especially ΣHCH. Beyond these factors, the consumption of beef and cow’s milk was linked to higher ΣHCH concentrations. This underscores the significant role that maternal dietary habits play in determining OCP levels in breast milk and the resulting health risks for women. Additionally, levels of ΣHCH and cis-chlordane (CHL) were influenced by a broader range of variables, including dietary habits, menstrual patterns, and histories of hormonal or infertility treatments. This scientific report suggests that exposure to pesticides can be harmful to newborns, as it was heavily present in breast milk and can lead to further accumulation of toxins in their undeveloped bodies [64].

Dwivedi et al. also detected OCPs residues in cord and maternal blood through GC-MS; the highest concentrations of OCPs, i.e., dieldrin and aldrin, were found in cord blood and maternal blood, respectively, at 2.69 mg/l and 3.26 mg/l [65]. These are a few examples of research studies that have documented the existence of agrochemical metabolites in human biological specimens in India. Similar findings have been observed in other countries. For instance, a survey conducted in Yucatan City, Mexico, found that prolonged pesticide exposure among the Mayan population was due to polluted drinking water. Researchers collected breast milk samples from Mayan women residing in coastal (Maxcanu) areas, agricultural fields (Peto), and metro areas (Kanasin) and tested them for OCPs. The analyses conducted revealed significant concentrations of OCPs residues, including 1.92 mg/kg of endrin and 18.43 mg/kg of heptachlor epoxide in the urban areas; as well as 2.10 mg/kg of dieldrin, 0.117 mg/kg of endosulfan II, 0.103 mg/kg of heptachlor, 0.178 mg/kg of endrin, and 0.127 mg/kg of endrin aldehyde in the primary agricultural area and along the western coastline [66]. The gravity of these findings was underscored by comparing them to the Codex Alimentarius (FAO/WHO) maximum residue limits (MRLs). The allowed MRL of OCPs in the milk sample for aldrin, dieldrin, and heptachlor are 0.006 mg/kg, endosulfan 0.01 mg/kg, and for DDT is 0.002 mg/kg [67].

Studies conducted in various countries have detected pesticide residues in breast milk. These findings have reported DDT concentrations in breast milk samples at levels of 1.365 μg/l in the USA [68], 14.46 μg/l in Ethiopia [69], 0.063 μg/l fat from Australia [70], 0.119 μg/l fat in Japan [71], and 1.621 μg/l fat in Poland [72] (Fig.4).

Figure 4.

This figure illustrates the concentrations of pesticide metabolites reported in female biological samples.

Pesticide Exposure and Its Correlation with Thyroid Disorder in Females

The thyroid is an endocrine gland in vertebrates that secretes thyroid hormones necessary for human metabolism, growth, and development, cardiovascular homeostasis, and the immune system [73]. Homeostasis of the thyroid can be interrupted in humans by several varieties of synthetic and organic chemicals, including pesticides [74]. Several reports revealed that thyroid hormone and pesticide-chlorinated compounds have structural similarities. In 1990, Van den Berg demonstrated in their study that DDT and its metabolites, like p,p'-DDD and o,p'-DDD, in addition to related chemicals like dicofol, are known to be endocrine disruptors that interfere with thyroid hormone carriers. Further, another study reported in experimental animals that several synthetic pesticides that contain halogen elements could interfere with thyroxine binding locations, leading to the interruption of thyroid hormone homeostasis, resulting in increased concentrations of thyroid-stimulating hormone (TSH) via the feedback regulatory process of the pituitary thyroid axis [75].

Rathore et al. investigated pesticide exposure among women in Jaipur, India, finding that those with hypothyroidism had significantly higher total pesticide residues (18.83 ± 2.19 ppm) than euthyroid women (14.68 ± 0.98 ppm). Additionally, among all evaluated pesticides, the concentrations of p,p′-DDT and its metabolites were higher in all subjects, whereas the level of dieldrin was significantly higher in hypothyroid women, i.e., 5.38 ± 1.23 ppm. These concentrations are alarming when compared with the 1977 FAO/WHO Joint Meeting on Pesticide Residues (JMPR) safety standards. The JMPR set the provisional tolerable daily intake (PTDI) for dieldrin at only 0.1 μg/kg body weight, indicating that the serum levels evaluated in the Jaipur study reflect high environmental bioaccumulation of the pesticide [76].

A cross-sectional study was conducted in China from hair matrix samples collected in 2016 to determine the correlation between specific pollutants and thyroid hormone levels in healthy Chinese women (n=196) aged 25 to 45. Researchers measured the concentration of pollutants and thyroid hormones in the first 12 centimetres of hair taken from the scalp. The findings of the study demonstrated a significant association between hair T4 and triiodothyronine (T3) levels and pentachlorophenol (PCP), dimethyl phosphate (DMP), β-HCH, and 3-methyl-4-nitrophenol (3Me4NP). Other pesticides, such as diethyl-thiophosphate (DETP), 3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethyl cyclopropane carboxylic acid (ClCF₃CA), metolachlor, difenoconazole, and tebuconazole, were specifically linked to T4 levels, while trans-3-(2,2-dichloro vinyl)-2,2-dimethyl cyclopropane-carboxylic acid (Cl₂CA), imidacloprid, and 2,4-dichlorophenoxyacetic acid (2,4-D) showed associations with T3 levels among others [77] (Table 1).

Table 1.

Summary of research on pesticide exposure and female thyroid disorder

Pesticide Effect on Female Reproductive Hormone

Pesticides are one of the major causes of a growing percentage of female infertility worldwide among humans due to several reasons, including endocrine disruption, genetic mutations, and compromised cellular components that disrupt signalling pathways and interrupt the equilibrium between oxidative and antioxidant factors. Reactive oxygen species (ROS) are highly reactive and unstable molecules that generate free radicals and ultimately lead to oxidative stress and perceived threats to the reproductive system [78,79]. These pesticides not only pose risks for reproductive disorders but also affect future generations, particularly in women.

Thus, non-occupational exposure to environmental toxicants, including pesticides, has increased in the last few decades and needs greater attention due to its damaging effect on reproductive organs. Previous experimental studies suggested that pesticide exposure at high concentrations alters endocrine function, disrupting the thyroid, gonadotropin, and signalling of sex-steroid hormones [80-83]. Additionally, it causes oxidative stress and alters sexual development, fecundity, and pregnancy issues [40, 84-87].

However, data on ongoing human exposure to environmental toxicants, such as pesticides, remains controversial due to varying investigation methodologies, including differences in exposure assessment and challenges in controlling for confounding factors, and this has led to conflicting conclusions about their impacts [88-91]. Moreover, there are specific concerns regarding chronic exposure to OPPs, which have been linked with endocrine disruption, including weight loss, anaemia, anorexia, hepatic dysfunction, and delayed neuropathy [92-94]. This controversy highlights the necessity for further research into how these chemicals interact with hormonal systems. In addition to OPPs and other classes of pesticides, such as OCPs, can also imitate and mimic estrogenic mechanisms by acting as agonists that promote transcriptional activation of estrogen-responsive genes, especially imitating the action of estrogen and potentially disrupting normal hormonal signalling pathways [95]. Therefore, it is critical to understand these interactions because they may contribute significantly to inducing adverse reproductive outcomes.

Mechanism of Action of OCPs and OPPs

Several studies reported that OCPs and OPPs disrupt the normal function of endocrine hormones, including estrogen, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and TSH [96]. These hormones regulate key reproductive processes such as the menstrual cycle, ovulation, implantation, and fetal development, as well as ovarian function [97, 98]. Disruption of these hormonal systems can lead to infertility, pregnancy failure, and other reproductive health problems. The accompanying Fig. 5 illustrates the effects of these endocrine disturbances.

Figure 5.

Effects of organochlorine (OCPs) and organophosphate pesticides (OPPs) induced endocrine disruption. This figure summarizes the potential adverse effects of OCPs and OPPs resulting from the disruption of key endocrine hormones

Molecular Pathways of Pesticide Toxicity: From Cellular Stress to Genetic Modification

OCPs and OPPs exposure triggers complex toxicological processes that disturb cellular homeostasis, induce oxidative stress, mitochondrial impairment, disrupt endocrine signaling, and epigenetic modifications. These molecular shifts lead to molecular disruption, specifically neurodegeneration, metabolic impairment, and reproductive dysfunction.

Reproductive toxicity caused by OCPs and OPPs

OCPs are highly effective organic synthetic pesticides that eradicate parasitic diseases. During World War II, the DDT application was widely used for the eradication of malaria and typhus parasites. This period marked a significant increase in pesticide production at the industrial level and established a pivotal moment in history for pesticide use [130]. However, in the 1970s, some researchers revealed that OCPs were highly persistent in the environment, non-biodegradable, and resistant to biological, photolytic, and chemical degradation. The low solubility of OCPs with the presence of chlorine atoms and toxic metabolites makes them more hazardous for higher organisms [50, 131].

Humans and many organisms have complex biochemical pathways for detoxifying and excreting environmental toxicants. However, these mechanisms do not completely prevent OCPs from being stored in lipids and fatty tissues [132, 133]. Furthermore, OCPs' microbial degradation is difficult; they persist in the environment and can be transported long distances. Traces of OCPs have even been detected in the Arctic region, demonstrating their widespread distribution [134]. Some persistent organic pollutants (POPs) have been regulated for decades [135], but are still frequently detected in humans. OCPs can interfere with essential mechanisms involved in the growth and development of fetuses [6]. Additionally, they can induce genotoxicity, neurotoxicity, and carcinogenic risks, and they are also associated with various chronic disorders [136-142].

According to the study of Elsharkawy and El-Nisr, OCPs like methoxychlor at high concentrations increased recurrent implantation failure, enhanced ovarian follicular atresia, and downregulated ovulation [143]. OCPs, specifically p,p′-DDT and p,p′-DDE, were reported to be significantly high in serum samples of Chinese women in Shanghai, and they were significantly associated with the high dietary intake of animal fat [144]. Chen et al. also found a link between γ-HCH and infertility among Taiwanese women who were exposed to OCPs through high dietary intake of animal fat via milk and meat [64].

A case-control study was conducted on women to determine the link between DDT and spontaneous abortion. The result of the study showed that the DDT metabolite DDE level was increased in maternal serum, and it was related to an elevated risk for spontaneous abortion [145]. Another study was conducted in Germany; 31 women and 16 men from Tanzania and 21 couples from Germany were included (n=89) who were attending a reproductive unit, HCH, pentachlorophenol, and polychlorinated biphenyls (PCBs) were examined, and levels of these pesticides were significantly increased in women with endometriosis or suffering from spontaneous abortion. The accumulation pattern of insecticides DDT, its metabolite DDE, and dieldrin differed significantly. In Tanzanian women the levels of DDT+DDE and dieldrin were considerably higher in serum and follicular fluid compared to German women (dieldrin serum: 0.50±0.07 μg/kg vs. 0.02±0.01 μg/kg; dieldrin follicular fluid: 0.17±0.02 μg/kg vs. 0.03±0.01 μg/kg; DDT+DDE serum: 15.92±2.04 μg/kg vs. 0.91±0.13 μg/kg; DDT+DDE follicular fluid: 6.06±1.47 μg/kg vs. 0.58±0.10 μg/kg). Moreover, in German women, a lower conception rate with high serum concentrations of DDT and DDE was also observed, suggesting a specific adverse effect of DDT on pregnancy success [146]. Furthermore, Gerhard et al. reported an association between increased DDT levels and low conception rates in some women [147]. Supporting this, Windham et al. also suggested that DDE may affect ovarian function and, consequently, impact pregnancy rates, but there was no effect of PCBs on female reproduction; however, DDT did affect ovarian function and pregnancy rates. Moreover, high levels of DDE [148] and DDT [149] were connected with luteal phase deficiency and short menstrual cycles. Hence, as a result, these women suffered from premature ovarian failure (POF), which was defined as the end of menstrual cycles and categorized by low levels of anti-Müllerian hormone (AMH) in blood, which is very important for conception [150]. In summary, according to these studies, OCPs stored in the female body could cause several negative impacts on endocrine disruption, damage, recurrent abortions, preterm birth, and neurodevelopment delays in children [151,152].

OPPs are widely used in agriculture to manage and control crop diseases and enhance crop production. However, their extensive application has raised environmental and health concerns. Human exposure to OPPs causes chronic problems and reproductive disorders [153-155]. According to several studies, OPPs exposure alters reproductive system functions, including hormone imbalance, irregular menstrual cycles, and alteration in ovarian weight. Yet, the exposure of OPPs to female infertility is indistinct [156]. The mechanism of action of OPPs leads to neurotoxicity, cellular toxicity, and reproductive toxicity [157-159].

Moreover, like OCPs, OPPs can also alter the concentration of endocrine hormones FSH, LH, progesterone, and estrogen through the HPG, initiating sexual dysfunction, which leads to infertility [160-162]. OPPs are transformed into a toxic oxide form through bioactivation and subsequently detoxified into dialkyl phosphate (DAP) metabolites [163], and most OPPs have similar metabolism; therefore, DAP metabolites are easily detected in urine samples [164]. OPPs have a short half-life, without significant storage in the body, and are defecated in urine [165-167]. Both in vivo and in vitro experimental research demonstrated the adverse results of OPPs on reproductive mechanisms in females, with imbalanced progesterone levels, a decreased fertility rate, and excessive proliferation of the cells of the endometrium, or uterus's inner lining [168, 169].

According to Bonilla et al., a 250 μM concentration of malathion exhibits acute toxicity after 24 hours of exposure in vitro cultured mouse oocytes. Results showed a significant decrease in oocyte survival, and it also reduced the follicular pool by enhancing the occurrence of follicle degeneration in a dose-time-dependent manner [170]. This occurs due to oxidative stress-mediated granulosa cell apoptosis, which additionally increases the generation of free radicals. According to Erthal-Michelato et al. malathion-induced cell proliferation promotes cell survival and instigates oxidative damage during peripubertal periods to the female reproductive system in rats [171]. Further, in another dose-dependent study, exposure to malathion (OPP) and endosulfan (OCC) induced cellular and biochemical toxicity. The insecticide endosulfan's impact on ovarian function was evaluated in hemicastrated virgin Swiss albino mice for 15 consecutive days by oral administration at daily doses of 1.5, 3, 6, and 9 mg/kg. Endosulfan treatment significantly inhibited compensatory ovarian hypertrophy. Furthermore, the observed increased in atretic follicles and the disrupted estrous cycle suggested that endosulfan may act either through direct ovarian toxicity or by interfering with the hypothalamo–hypophyseal–ovarian (HHO) axis [172].

Female albino rats received daily intraperitoneal injections of methyl parathion at doses ranging from 1.5 to 3 mg/kg for 15 days, beginning on the day of estrus. The treatment induced irregular estrous cycles and altered the duration of individual cycle stages; specifically, the proestrus and diestrus phases were significantly disrupted in the 2.5 and 3 mg/kg treatment groups [173]. Histological experimental studies of Wistar albino rats revealed that after endosulfan and malathion exposure, ovarian tissue size and healthy follicle number decreased, and atretic follicle number was enhanced [172, 173].

Guney et al., observed that Wistar-albino rats exposed to methidathion (5 mg/kg body weight; 0.15 LD₅₀ in corn oil) via gavage five days a week for four weeks exhibited significant irregularities in the estrous cycle. This study also reported a significant increase in malondialdehyde (MDA) levels, alongside a reduction in the total number of estrous cycles and a shortening of all cycle phases except diestrus, compared to the control group [174]. In a comparable study, Koc et al. identified elevated MDA levels and histological damage in Wistar albino rats following combined exposure to endosulfan and malathion. Notably, while a group exposed to low doses of endosulfan and malathion (11 mg/kg/day) showed no visible changes to external ovarian morphology. Conversely, the group exposed to high doses (33 mg/kg/day) treatment led to a significant reduction in ovarian tissue size [175].

The oviductal membrane has an important role in fertilization and transportation of the zygote to the uterus for implantation [176]. It has been reported that OPP causes impairment to the fallopian tube via oxidative stress. Methyl parathion pesticide-initiated lipid peroxidation (LPO) results in the omission of microvilli and a significant deprivation of kinocilia on the oviducal membrane in rats [177] (Table 2).

Table 2.

OCPs and OPPs impact on female reproductive health

These findings reported that exposure to OPPs and OCPs poses a dual threat to reproductive health. They are not only toxic but also specifically disruptive to reproductive homeostasis and the physical integrity of the gonads.

Future Direction

Future studies should focus on investigating how OCPs and OPPs induce specific epigenetic alterations, such as DNA methylation or histone modifications, that affect the expression of genes perilous for ovarian function, oocyte maturation, or endometrial receptivity. Further research on the methylation status of genes required for hormone synthesis, folliculogenesis, or DNA repair pathways in women exposed to these pesticides. Research should also explore how OCPs and OPPs affect mitochondrial DNA, energy production (ATP), and the generation of ROS within ovarian cells (e.g., granulosa cells, oocytes). This could lead to premature ovarian aging or poor oocyte quality and epigenetic modulation of ovarian gene expression by OCPs and OPPs in women with unexplained infertility.

Strengths and Limitations of the Study

The article highlighted a significant gap in today’s toxicological data, specifically on OCPs and OPPs, rather than pesticides as a broad category. This focus is important because these two pesticide categories work in different ways when it comes to affecting neuronal and hormonal control. This review not only covers the broad spectrum of studies related to epidemiological exposure but also includes a focus on high-dose, short-term animal studies. But it also included research into long-term, low-level exposure from the environment and diet, which reflects the everyday experiences of the general population, instead of just extreme cases in the workplace, especially for women. The literature on exposure to OCPs and OPPs and female reproductive disorders mainly consists of cross-sectional and case-control studies, while there is a shortage of research articles on cohort studies. Moreover, a careful review indicates that studies reporting 'null' findings often fail to account for important factors. These factors include dietary intake, a key route of exposure for lipophilic OCPs, and body mass index (BMI). Finally, there is a lack of clinic-based research directly assessing the impact of OCPs/OPPs on thyroid disorders in females.